Merck Announces Results from Phase 2 Study of Investigational Chronic Hepatitis C Treatment Grazoprevir/Elbasvir in Genotype 1 Infected Treatment-Naïve and Difficult-to-Cure Patients

Final Results from the C-WORTHy Study (Parts A and B) Presented at The Liver Meeting^® and Published in The Lancet

First Wave of Phase 3 Development Program for Grazoprevir/Elbasvir is Fully Enrolled; Merck Plans to Submit New Drug Application in 2015

Tuesday, November 11, 2014 8:00 am EST

BOSTON--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced the presentation of results from a multi-arm Phase 2 clinical trial evaluating grazoprevir/elbasvir (MK-5172/MK-8742, the company’s investigational NS3/4A protease inhibitor and NS5A inhibitor, respectively) with or without ribavirin (RBV) in treatment-naïve and previously-treated (with peg-interferon/ribavirin [PR]) patients with chronic hepatitis C virus (HCV) genotype 1 (GT1) infection -- the C-WORTHy study (Parts A and B). The final results were presented in oral sessions at the 65^th American Association for the Study of Liver Diseases (AASLD) Annual Meeting (also known as The Liver Meeting^®) and published as separate papers online in The Lancet.

“Merck is committed to developing an efficacious, well-tolerated therapy suitable for a broad spectrum of patients with HCV,” said Dr. Eliav Barr, vice president, infectious diseases, Merck Research Laboratories. “We are encouraged by the findings for grazoprevir/elbasvir in the C-WORTHy trial and look forward to advancing our broad Phase 3 program, which includes hard-to-cure patients that are of the highest need and least studied to date.”

Interim results from the C-WORTHy study were presented in April 2014 at the 49^th Annual Meeting of the European Association for the Study of the Liver (EASL) and announced by Merck.

Results for Treatment-Naïve Cirrhotic Patients and PR Null-Responders

The results for HCV mono-infected treatment-naïve GT1 patients with cirrhosis and GT1 prior null-responders with or without cirrhosis treated with grazoprevir/elbasvir, with or without ribavirin, for 12 weeks or 18 weeks are shown in table 1. The rates of sustained viral response,ⁱ 12 weeks after the completion of therapy (SVR12) were greater than, or equal to, 90 percent regardless of treatment duration or co-administration of RBV.

The rate of virologic failure was five percent (6/123) in treatment-naïve cirrhotic patients and three percent (4/130) in the null-responder population. Treatment was generally well-tolerated. The most common adverse events associated with the administration of grazoprevir/elbasvir in combination with or without RBV were: fatigue (26%), headache (23%) and asthenia (14%). There were no early discontinuations due to adverse events with grazoprevir/elbasvir and no clinically significant abnormalities observed in routinely evaluated biomarkers.

Results for HCV Mono-Infected and HIV/HCV Co-Infected Patients

Treatment-naïve, non-cirrhotic mono-infected GT1 patients and non-cirrhotic HCV GT1 /HIV co-infected patients treated for 12 weeks with grazoprevir/elbasvir with or without RBV, demonstrated high rates of SVR12, as seen in table 2. Among this patient population treated for 12 weeks, the overall rate of virologic failure was four percent (7/188), including three breakthrough failures and four relapses, in both mono- and co-infected patients. In patients treated for eight weeks, the rate of virologic failure was 17 percent (5/30), with five relapses. The most common adverse events with or without RBV were fatigue (23%), headache (20%), nausea (15%) and diarrhea (10%). There were no early discontinuations due to adverse events with grazoprevir/elbasvir and no clinically significant abnormalities observed in routinely evaluated biomarkers.

About the C-WORTHy Study

C-WORTHy is a randomized, dose response, parallel-group, multiple-site, double-blind clinical trial comparing diverse patient populations exposed to different durations of treatment of grazoprevir/elbasvir with or without RBV in patients with chronic HCV infection. In C-WORTHy Parts A and B, a total of 471 patients with chronic HCV GT1 infection with HCV RNA levels of ≥10,000 IU/mL were enrolled and randomized across 16 arms. The patients include hard-to-cure sub-populations, including treatment-naïve patients with liver cirrhosis (12- and 18-week arms, with and without RBV) and prior-null responder patients with and without cirrhosis (12- and 18-week arms, with and without RBV). The lead authors of The Lancet publications and presenters at The Liver Meeting^® are Dr. Eric Lawitz of The Texas Liver Institute and professor of medicine at The University of Texas Health Science Center, San Antonio, TX (C-WORTHy Cirrhotic Patients and Prior Null-Responders); and Dr. Mark Sulkowski, professor of medicine at The Johns Hopkins University School of Medicine, Baltimore, MD (C-WORTHy HCV Mono-Infected and HIV/HCV Co-Infected Patients).

About C-EDGE: Merck’s Phase 3 HCV Program

The results of the C-WORTHy study supported the advancement of grazoprevir/elbasvir into the Phase 3 clinical development program called C-EDGE. The Phase 3 C-EDGE program is evaluating grazoprevir/elbasvir with and without RBV in various genotypes and across a broad range of patient populations with chronic HCV infection, including treatment-naive patients and patients who previously failed PR therapy, patients with and without cirrhosis, patients with chronic kidney disease (including those on hemodialysis), patients with HIV/HCV co-infection, patients on opiate substitution therapy and patients with inherited blood disorders. Merck initiated the first C-EDGE study in April 2014, and the grazoprevir/elbasvir registration studies within the C-EDGE program – including C-EDGE TN (treatment-naïve), C-EDGE CO-INFXN (HIV/HCV co-infected) and C-EDGE TE (treatment-experienced) -- are now fully enrolled. Results from these trials are anticipated in the first half of 2015. Learn more at http://www.merck.com/clinical-trials/.

About Grazoprevir/Elbasvir

Grazoprevir/elbasvir (MK-5172/MK-8742) is an investigational, oral, once-daily, fixed-dose combination chronic HCV treatment, consisting of grazoprevir, an investigational oral, once-daily HCV NS3/4A protease inhibitor, and elbasvir, an investigational oral, once-daily HCV NS5A replication complex inhibitor. In October 2013, Merck announced that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy designation to grazoprevir/elbasvir for treatment of chronic HCV infection. Breakthrough Therapy designation is intended to expedite the development and review of a candidate that is planned for use, alone or in combination, to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints. Merck plans to submit the New Drug Application for grazoprevir/elbasvir in 2015.

Merck’s Commitment to HCV

For nearly 30 years, Merck has been at the forefront of the response to the HCV epidemic. Merck employees are dedicated to applying their scientific expertise, resources and global reach to deliver innovative healthcare solutions that support people living with HCV worldwide.

About Merck

Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebook and YouTube.

Merck Forward-Looking Statement

This news release includes “forward-looking statements” within the meaning of the safe harbor provisions of the United States Private Securities Litigation Reform Act of 1995. These statements are based upon the current beliefs and expectations of Merck’s management and are subject to significant risks and uncertainties. There can be no guarantees with respect to pipeline products that the products will receive the necessary regulatory approvals or that they will prove to be commercially successful. If underlying assumptions prove inaccurate or risks or uncertainties materialize, actual results may differ materially from those set forth in the forward-looking statements.

Risks and uncertainties include, but are not limited to, general industry conditions and competition; general economic factors, including interest rate and currency exchange rate fluctuations; the impact of pharmaceutical industry regulation and healthcare legislation in the United States and internationally; global trends toward healthcare cost containment; technological advances, new products and patents attained by competitors; challenges inherent in new product development, including obtaining regulatory approval; Merck’s ability to accurately predict future market conditions; manufacturing difficulties or delays; financial instability of international economies and sovereign risk; dependence on the effectiveness of Merck’s patents and other protections for innovative products; and the exposure to litigation, including patent litigation, and/or regulatory actions.

Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise. Additional factors that could cause results to differ materially from those described in the forward-looking statements can be found in Merck’s 2013 Annual Report on Form 10-K and the company’s other filings with the Securities and Exchange Commission (SEC) available at the SEC’s Internet site (www.sec.gov).

ⁱ Defined as HCV RNA below the limit of quantification or below the limit of detection at the last visit on record – 4, 8, 12, or 24 weeks after the completion of therapy.
ⁱⁱ Virologic failure is the inability to achieve or maintain suppression of viral replication to an HCV RNA level <200 copies/mL.

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Pam Eisele, 267-305-3558
Sarra Herzog, 201-669-6570
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Gilead Announces Harvoni Study Results in Chronic Hepatitis C Patients with Advanced Liver Disease and Those Who Failed Prior Treatment

Published: Nov 11, 2014 8:02 a.m. ET

- High Cure Rates in Nearly 800 HCV Patients with Advanced Liver Disease -

BOSTON, Nov 11, 2014 (BUSINESS WIRE) -- Gilead Sciences, Inc. GILD, +0.55% today announced results from several Phase 2 and Phase 3 studies evaluating investigational uses of Harvoni® (ledipasvir 90 mg/sofosbuvir 400 mg) for the treatment of chronic hepatitis C virus (HCV) infection in patients with limited or no treatment options, including patients with decompensated cirrhosis, patients with HCV recurrence following a liver transplant and patients who failed previous treatment with other direct acting antivirals. These data will be presented this week at the 65th Annual Meeting of the American Association for the Study of Liver Diseases (The Liver Meeting2014) in Boston.

“Chronic hepatitis C patients with advanced liver disease are among the most difficult to cure and traditionally have had limited or no treatment options,” said Norbert Bischofberger, PhD, Executive Vice President of Research and Development and Chief Scientific Officer, Gilead Sciences. “The data presented this week demonstrate that Harvoni provides high cure rates for patients with advanced liver disease, as well as for those who failed prior treatment with other antivirals, including sofosbuvir-based regimens.”

Harvoni was approved by the U.S. Food and Drug Administration and Health Canada in October 2014 and is the first once-daily single tablet regimen for the treatment of chronic HCV genotype 1 infection in adults. Applications are pending in the European Union, Japan and New Zealand.

Advanced Liver Disease

In a pooled analysis of Phase 2 and Phase 3 open-label studies (Oral #82) in more than 500 genotype 1 HCV infected patients with compensated cirrhosis who received Harvoni alone or with ribavirin (RBV) for 12 or 24 weeks, 96 percent of patients achieved sustained virologic response (SVR12). Patients who achieve SVR12 are considered cured of HCV infection.

Two prospective analyses from a Phase 2 open-label study (Study GS-US-337-0123) evaluating patients with decompensated cirrhosis and those with HCV recurrence following liver transplantation also are being presented. In the first subgroup (Oral #239), 108 genotype 1 and 4 infected patients with decompensated cirrhosis, including those with moderate hepatic impairment (Child-Pugh-Turcotte (CPT) Class B) and severe hepatic impairment (CPT Class C), received Harvoni plus RBV for 12 or 24 weeks. Overall, SVR12 rates were 87 percent (n=45/52) in the 12-week arm and 89 percent (n=42/47) in the 24-week arm.

The second subgroup (Oral #8) evaluated 12 or 24 weeks of Harvoni plus RBV among 223 genotype 1 and 4 patients who developed HCV recurrence following liver transplantation. Among non-cirrhotic patients, SVR12 rates were 96 percent (n=53/55) and 98 percent (n=55/56) following 12 and 24 weeks of treatment, respectively. For patients with compensated cirrhosis, SVR12 rates were 96 percent for both 12 weeks (n=25/26) and 24 weeks (n=24/25) of therapy. SVR12 rates among patients with decompensated cirrhosis were 81 percent for both 12 weeks (n=25/31) and 24 weeks (n=17/21) of therapy.

Retreatment of Patients Who Failed Prior Therapy

Study GS-US-337-0121 (Late Breaker Oral #LB-6) evaluated 155 genotype 1 patients with compensated cirrhosis who had failed prior treatment with pegylated interferon (PegIFN)/RBV and subsequently PegIFN/RBV plus a protease inhibitor. In this study, patients were randomized (1:1) to receive Harvoni plus RBV for 12 weeks or Harvoni alone for 24 weeks. Ninety-six percent (n=74/77) of those receiving Harvoni plus RBV for 12 weeks and 97 percent (n=75/77) of those receiving Harvoni for 24 weeks achieved SVR12.

In a second study (Oral #235), 51 genotype 1 patients who previously failed SOF/PegIFN/RBV, SOF/RBV or a SOF placebo/PegIFN/RBV treatment regimen received Harvoni plus RBV for 12 weeks. Twenty-nine percent of study patients (n=15/51) had cirrhosis. Ninety-eight percent (n=50/51) achieved SVR12 following 12 weeks of treatment with Harvoni plus RBV.

In all of these studies, Harvoni was well tolerated and its safety profile was generally consistent with that observed in clinical trials of Harvoni. Adverse events included fatigue, headache, nausea and anemia, which was more common among patients taking RBV. Grade 3/4 laboratory abnormalities were infrequent and included decreases in hemoglobin, which is consistent with RBV-associated anemia.

The safety and efficacy of Harvoni have not been established for the investigational uses described above.

Additional information about these studies can be found at www.clinicaltrials.gov.

Important Safety Information About Harvoni

Warnings and Precautions

Risk of Reduced Therapeutic Effect of Harvoni Due to P-gp Inducers: Rifampin and St. John’s wort are not recommended for use with Harvoni as they may significantly decrease ledipasvir and sofosbuvir plasma concentrations.

Related Products Not Recommended: Harvoni is not recommended for use with other products containing sofosbuvir (Sovaldi).

Adverse Reactions

Most common (greater-than or equal to 10 percent, all grades) adverse reactions were fatigue and headache.

Drug Interactions

In addition to rifampin and St. John’s wort, coadministration of Harvoni is also not recommended with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifapentine, and tipranavir/ritonavir. Such coadministration is expected to decrease the concentration of ledipasvir and sofosbuvir, reducing the therapeutic effect of Harvoni.

Coadministration of Harvoni is not recommended with simeprevir due to increased concentrations of ledipasvir and simeprevir. Coadministration is also not recommended with rosuvastatin or co-formulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate due to increased concentrations of rosuvastatin and tenofovir, respectively.

Consult the full Prescribing Information for Harvoni for more information on potentially significant drug interactions, including clinical comments.

About Gilead Sciences

Gilead Sciences is a biopharmaceutical company that discovers, develops and commercializes innovative therapeutics in areas of unmet medical need. The company’s mission is to advance the care of patients suffering from life-threatening diseases worldwide. Headquartered in Foster City, California, Gilead has operations in North and South America, Europe and Asia Pacific.

Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the possibility of unfavorable longer-term results from these studies and other ongoing and subsequent clinical trials involving Harvoni, alone or in combination with other products, for the treatment of HCV in other patient populations. As Harvoni is used over longer periods of time, Gilead may find new issues such as safety or drug resistance, which may require it to provide additional warnings or contraindications in the label, which could reduce the market acceptance of Harvoni. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2014, as filed with the U.S. Securities and Exchange Commission. All forward-looking statements are based on information currently available to Gilead, and Gilead assumes no obligation to update any such forward-looking statements.

U.S. Full Prescribing Information for Harvoni is available at www.gilead.com.

Harvoni is a registered trademark of Gilead Sciences, Inc.

For more information on Gilead Sciences, please visit the company’s website at www.gilead.com, follow Gilead on Twitter (@GileadSciences) or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

SOURCE: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Patrick O’Brien, 650-522-1936 (Investors)
Cara Miller, 650-522-1616 (Media)

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AbbVie to Present Results from Phase 2 PEARL-I Study in Genotype 4 Chronic Hepatitis C Patients at the Liver Meeting 2014

- Results demonstrated high response rates in adult chronic hepatitis C genotype 4 patients without cirrhosis

- Data underscore AbbVie's commitment to evaluating treatments across a range of patients with chronic hepatitis C virus infection

Nov 11, 2014

BOSTON, Nov. 11, 2014 /PRNewswire/ -- AbbVie (NYSE:ABBV) announced detailed results from its open-label Phase 2b study, PEARL-I, which demonstrated that 100 percent  of genotype  4 (GT4) patients who were new to therapy (n=42/42) or who had failed previous treatment with pegylated interferon (pegIFN) and RBV (n=49/49) achieved sustained virologic response rates at 12 weeks post-treatment (SVR₁₂) after taking AbbVie's investigational treatment with ribavirin (RBV). Additionally, 90.9 percent of patients who were new to therapy achieved SVR₁₂ (n=40/44) after taking the treatment without RBV. These data will be presented today during a poster session at The Liver Meeting® 2014.

"As many as 34 million people around the world are living with genotype 4 chronic hepatitis C, a population that is common in the Middle East and Africa, where it accounts for more than 80 percent of all hepatitis C cases,[i]" said Barry Bernstein, M.D., vice president, infectious disease development, AbbVie. "The data from PEARL-I represent another important step forward in realizing our commitment to advancing scientific knowledge in hepatitis C with the ultimate goal of providing treatment options to as many patients as possible."

PEARL-I studied AbbVie's all-oral, interferon-free investigational treatment combining two direct-acting antivirals (ABT-450/ritonavir and ombitasvir) with and without RBV for 12 weeks in non-cirrhotic adult patients with chronic genotype 1b (GT1b) and GT4 hepatitis C virus (HCV) infection.

There were no discontinuations due to adverse events in PEARL-I. The most commonly reported treatment-emergent adverse events (greater than 15 percent in any group) were headache (29-33 percent), asthenia (weakness) (24-33 percent), fatigue (7-18 percent), nausea (9-17 percent) and insomnia (5-16 percent). One patient had a grade 3 liver function test elevation (AST> five times the upper limit of normal), which was asymptomatic and resolved during continued dosing. Four patients with hemoglobin decreases (anemia) required RBV dose reductions; however, none of these patients required blood transfusions or medication to boost their red blood cell production. In the treatment-naïve group without RBV, on-treatment virologic breakthrough was reported in one patient (2 percent) and two patients (5 percent) experienced post-treatment relapse. There were no virologic failures in the other treatment arms.

About AbbVie's Investigational Two Direct-Acting Antiviral HCV Treatment
AbbVie's proposed all-oral antiviral treatment consists of the fixed-dose combination of ABT-450/ritonavir (150/100mg) co-formulated with ombitasvir (25mg) dosed once daily, co-administered with weight-based ribavirin (1000mg or 1200mg in divided doses twice daily). The combination of two direct-acting antivirals, each with distinct mechanisms of action, targets and inhibits specific HCV proteins in the viral replication process.

About AbbVie's HCV Clinical Development Program
The AbbVie HCV clinical development program is intended to advance scientific knowledge and clinical care by investigating interferon-free, all-oral treatments with and without ribavirin with the goal of achieving high sustained virologic response rates in as many patients as possible. AbbVie's development programs combining two direct-acting antivirals are studying additional hepatitis C virus (HCV) genotypes.

ABT-450 was discovered during the ongoing collaboration between AbbVie and Enanta Pharmaceuticals (NASDAQ: ENTA) for HCV protease inhibitors and regimens that include protease inhibitors. ABT-450 is being developed by AbbVie for use in combination with AbbVie's other investigational medicines for the treatment of hepatitis C.

Safety Information for Ribavirin and Ritonavir
Ribavirin and ritonavir are not approved for the investigational use discussed above, and no conclusions can or should be drawn regarding the safety or efficacy of these products for this use.

There are special safety considerations when prescribing these drugs in approved populations.

Ritonavir must not be used with certain medications due to significant drug-drug interactions and in patients with known hypersensitivity to ritonavir or any of its excipients.

Ribavirin monotherapy is not effective for the treatment of chronic hepatitis C virus and must not be used alone for this use. Ribavirin causes significant teratogenic effects and must not be used in women who are pregnant or breast-feeding and in men whose female partners are pregnant. Ribavirin must not be used in patients with a history of severe pre-existing cardiac disease, severe hepatic dysfunction or decompensated cirrhosis of the liver, autoimmune hepatitis, hemoglobinopathies, or in combination with peginterferon alfa-2a in HIV/HCV co-infected patients with cirrhosis and Child-Pugh score ≥6.

See approved product labels for more information.

About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. AbbVie employs approximately 25,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

Forward-Looking Statements
Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995.  The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements.  AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements.  Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry.  Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2013 Annual Report on Form 10-K and in Item 1A, "Risk Factors" of Part II of AbbVie's second quarter 2014 Quarterly Report on Form 10-Q, which have been filed with the Securities and Exchange Commission.  AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

[i] Khattab MA, et al. Management of hepatitis C virus genotype 4: Recommendations of an International Expert Panel. J Hepatol. 2011; 54: 1250–1262

SOURCE AbbVie

For further information: Media: Stefanie Prodouz, +1 (224) 637-0971, stefanie.prodouz@abbvie.com; or Javier Boix, +1 (847) 937-6113, javier.boix@abbvie.com; or Investor Relations:Liz Shea, +1 (847) 935-2211, liz.shea@abbvie.com

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Unique 'pay if you clear' proposal for new hepatitis drug

13 October 2014 Last updated at 11:35 ET

By Reevel Alderson BBC Scotland's social affairs correspondent

More than 37,000 people in Scotland have chronic hepatitis C - but only half have been diagnosed

The NHS in Scotland could be reimbursed for the cost of a new hepatitis drug if sufferers fail to clear the virus.

The novel proposal was revealed after the drug Olysio was cleared for use by the Scottish Medicines Consortium (SMC).

The drug's manufacturer claims the move would help cut prescribing costs.

It is estimated Scotland wastes up to £44m each year on medicines for all conditions that are unused, ineffective or are taken incorrectly.

The 'Pay If You Clear' scheme would come into effect if patients treated with the drug do not become free of the hepatitis C virus (HCV) after 12 weeks.

SMC has approved the drug, whose generic name is simeprevir, for use within NHS Scotland. The 'Pay If You Clear' scheme is awaiting a formal decision by NHS Scotland.

Appropriate treatment

The drug will be used to treat patients with chronic HCV infection, including those for whom treatment has previously failed.

The manufacturer, Janssen, will pay for pre-treatment blood tests for patients to predict whether the drug is likely to be effective before treatment is initiated.

Continue reading the main story

“Start Quote

We must not forget the importance of prevention, earlier diagnosis and better testing strategies”

End Quote Charles Gore Hepatitis C Trust

Any patient who does not respond to treatment within four weeks will be offered alternative therapies.

Dr John Dillon, consultant hepatologist and gastroenterologist at Ninewells Hospital in Dundee, welcomed the decision by SMC.

"This decision provides us with another treatment option which is convenient for patients and more affordable to NHS Scotland than some other treatments," he said.

"To be able to predict a person's response to treatment, prior to them embarking on the medicine, is a particularly useful factor in managing hepatitis C care.

"It means we can select the most appropriate treatment option in a cost-efficient manner."

Charles Gore, chief executive of The Hepatitis C Trust, said: "Decisions such as this from the SMC provide us with a key milestone for our campaign to eliminate hepatitis C.

"However, we must not forget the importance of prevention, earlier diagnosis and better testing strategies."

Charities claim there are more than 37,000 Scots with chronic HCV, only 55% of whom have been diagnosed, because often it has no symptoms.

Of those who develop hepatitis C an estimated 30% will develop cirrhosis of the liver or cancer.

Hepatitis C is the most common reason for liver transplants in Europe.

Source

Novira Therapeutics Announces Presentation of Phase 1a Safety and Pharmacokinetic Data for NVR 3-778

Phase 1b Clinical Studies Ongoing in Patients with Chronic HBV Infection

DOYLESTOWN, Pa., Nov. 10, 2014 /PRNewswire/ -- Novira Therapeutics, Inc., a privately held biopharmaceutical company developing novel therapies for curative treatment of chronic hepatitis B virus (HBV) infection, today announced the presentation of Phase 1a safety and pharmacokinetic data for its lead HBV antiviral candidate, NVR 3-778 (also known as NVR-1221), in a late-breaking poster presentation at the 2014 annual meeting of the American Association for the Study of Liver Diseases in Boston. Dr. Edward J. Gane, Chief Hepatologist and Deputy Director of the New Zealand Liver Transplant Unit at Auckland City Hospital in Auckland, New Zealand is the lead author on the poster and the principal clinical investigator for the study.

The randomized, placebo-controlled Phase 1a trial enrolled 40 healthy adult volunteers to assess the safety and tolerability of NVR 3-778 after single oral doses of 50 to 800 mg/day, followed by an assessment of 200 mg once-daily dosing for 14 days. The study results indicated that NVR 3-778 was well-tolerated at all doses. There was no pattern of treatment-related or dose-related clinical adverse events (AEs), and no serious or severe AEs. All AEs were of common types, and most were not attributed to study drug treatment. The AEs were all transient and mild (grade 1) in severity except for two grade 2 AEs not attributed to study treatment (sprain and tooth pain). The pharmacokinetic profile of NVR 3-778 indicated substantial dose-related plasma levels that were consistent across the subjects within each dosing cohort. At doses of 200 mg or more, plasma concentrations of NVR 3-778 remained above in vitro HBV-inhibitory concentrations for more than 24 hours, supporting evaluation of once-daily dosing in HBV patients.

"These encouraging Phase 1a results indicate that NVR 3-778 was well-tolerated at all dose levels in human volunteers, and once-daily doses of 200 mg or more provided systemic levels of NVR 3-778 high enough to potentially be associated with antiviral efficacy in hepatitis B patients," said Nathaniel Brown MD, Novira's Chief Medical Officer. "The Phase 1a results support advancement to Phase 1b testing in patients with chronic HBV infection, which is now underway. The Phase 1b clinical study is designed to evaluate the safety and antiviral efficacy of NVR 3-778 in HBV patients as both a single agent and in combination with current HBV therapies after a four week dosing period."

About NVR 3-778

NVR 3-778 is a small molecule, direct acting antiviral, for oral administration in patients with Chronic Hepatitis B (CHB) that inhibits the HBV core or capsid protein. HBV core is a novel and promising drug target with multiple activities required for viral replication and persistence. Inhibition of HBV core protein function by NVR 3-778 offers the potential for more efficient suppression of the virus leading to improved durable viral suppression and functional cure rates.

About HBV

Hepatitis B infection presents a significant unmet medical need with an estimated 350 million people worldwide living with chronic HBV infection. A significant number of patients with chronic infection incur a higher risk of developing cirrhosis and cancer. It is estimated that 60% of hepatocellular carcinoma (liver cancer) is a direct consequence of HBV infection. Current drugs approved for the management of CHB include PEG-Interferon and nucleot(s)ides which can effectively suppress virus replication, but rarely lead to a cure.

About Novira Therapeutics

Novira Therapeutics, Inc., is a privately held biopharmaceutical company focused on discovery and development of first-in-class antiviral drugs for the treatment of chronic HBV infection (CHB), a global disease with a high level of unmet medical need. The company is employing innovative chemistry and biology technologies to discover small molecule inhibitors of the HBV core or capsid protein as well as other drugs with novel mode of action. The company's novel antivirals will offer the potential to address the limitations of current CHB therapies when used either as mono-therapy or in combination with existing standards of care.

For more information, visit www.noviratherapeutics.com.

Contacts:

Corporate Contact
Christian S. Schade
Chief Executive Officer
cschade@noviratherapeutics.com

Media Contacts
David Schull    
Matt Middleman, M.D.             
Russo Partners      
T: (212) 845-4271                
T: (212) 845-4272
david.schull@russopartnersllc.com
matt.middleman@russopartnersllc.com

SOURCE Novira Therapeutics, Inc.

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Choose Your Tests Wisely: Advice From the AASLD

Medscape Gastroenterology

Lauri R. Graham, Raphael B. Merriman, MD, FRCPI

November 10, 2014

Editor's Note: Choosing Wisely®, an initiative of the American Board of Internal Medicine (ABIM) Foundation, comprises evidence-based recommendations from specialty organizations on commonly used tests and procedures. The goal of the campaign is to use these recommendations as the starting point for discussions between clinicians and patients about avoiding unnecessary care. Choosing Wisely launched in 2012 with five recommendations each from nine specialties; more than 60 specialty societies have now joined the campaign, with new lists continuing to be published through 2014 and more planned beyond that. Medscape interviewed Raphael B. Merriman, MD, of the American Association for the Study of Liver Diseases (AASLD), who helped craft its Choosing Wisely recommendations.

Medscape: Would you give a brief history of AASLD's involvement in the Choosing Wisely campaign, and why you believed this would be important?

Dr Merriman: We welcomed the opportunity to embrace this leadership challenge to help physicians be better stewards of finite healthcare resources.

The AASLD established the Choosing Wisely task force in December 2013 to develop its list of recommendations. Members were selected from the AASLD practice guidelines committee to broadly represent varying practice settings and subspecialty expertise within the field of hepatology. Hepatologists with methodological experience in evidence-based medicine were also included. The working group solicited recommendations from the entire AASLD membership that would be considered for inclusion in the list of five tests or treatments that physicians and patients should question. These recommendations were then rated on the basis of judgments related to harm, benefit, and excess resource utilization.

On the basis of voting by the working group, as well as a literature review of supporting data, a total of 10 suggestions were identified. Subsequently, voting by the working group generated the final top five recommendations. These top five recommendations were submitted and approved by the AASLD Governing Board.

Medscape: I'd like to go through the recommendations and ask you how they were selected. Could you also speak briefly about the evidence behind the recommendations? The first recommendation is: Don't perform surveillance esophagogastroduodenoscopy (EGD) in patients with compensated cirrhosis and small varices without red signs treated with nonselective beta-blockers for preventing a first variceal bleed.

Dr Merriman: This first recommendation is based on a recommendation in the AASLD practice guidelines related to portal hypertension and variceal bleeding. It relates to patients with cirrhosis and small varices that have not bled and do not have criteria for an increased risk for bleeding (that is, Child-Pugh class A and the absence of red signs on endoscopic variceal evaluation); for these patients, beta-blockers can be used. In patients with cirrhosis and medium or large varices that have not bled and, again, are not at the highest risk for bleeding (that is, Child-Pugh class A and no red signs), beta-blockers are preferred. The doses of the beta-blockers should be adjusted to the maximum tolerated dose.

In both of these clinical scenarios, follow-up EGD is not necessary. This practice would reduce the need for non-indicated upper gastrointestinal endoscopy.

Medscape: Your second recommendation is: Don't continue treatment for hepatic encephalopathy indefinitely after an initial episode with an identifiable precipitant.

Dr Merriman: This reflects a recommendation made in the recently published practice guideline on hepatic encephalopathy, which was jointly developed by the AASLD with the European Association for the Study of the Liver.

Patients may have episodes of hepatic encephalopathy with precipitating factors that can be identified and controlled, such as recurrent infections or variceal hemorrhage. In those circumstances where the precipitating factors are clearly identified and well controlled, the treatment of hepatic encephalopathy may not necessarily be indefinite and indeed could be discontinued.

This is important because in the past, it has been common practice to continue the prophylactic treatment of hepatic encephalopathy indefinitely after it was initiated, even though there was little basis to actually support that. So this recommendation has significant implications to reduce unnecessary use of therapeutics to prevent recurrent hepatic encephalopathy.

Medscape: Your third recommendation is: Don't repeat hepatitis C viral load testing outside of antiviral therapy.

Dr Merriman: This is an important, topical, and relevant recommendation, particularly in the context of the transformative changes occurring in the field of hepatitis C therapeutics with the imminent availability of a whole host of new, highly effective hepatitis C antiviral agents that are curing hepatitis C.

Highly sensitive serum assays of hepatitis C RNA are expensive. Performing these assays is appropriate at the time of diagnosis of hepatitis C and as part of antiviral therapy, typically at the beginning of and possibly during therapy, and also after therapy is completed. Outside of these circumstances, there is little benefit to measuring the hepatitis C viral RNA load, as it typically does not affect either the clinical management or outcomes.

This recommendation is of particular relevance to patients because, oftentimes, there is a mistaken patient perception that the testing is needed, that there is significance to quite modest changes in the hepatitis C viral load, and that it actually affects clinical outcomes. Therefore, this recommendation will prompt a discussion that should hopefully reduce the need for unnecessary virologic testing.

Medscape: Your fourth recommendation is: Don't perform CT or MRI routinely to monitor benign focal lesions in the liver unless there is a major change in clinical findings or symptoms.

Dr Merriman: Many patients have focal liver lesions detected by imaging—often incidentally—who don't have underlying liver disease and that are determined to be benign. Those who demonstrate both clinical and radiologic stability do not need repeated imaging as the likelihood of evolving into neoplastic lesions is very low (with the exception of hepatocellular adenoma). Clinical stability implies the absence of any new symptoms related to these focal liver lesions. This recommendation stems from a common perception that even after clinical and radiologic stability of the benign focal lesions has been demonstrated, that imaging needs to be repeated indefinitely. This recommendation provides guidance to support discontinuing serial imaging in these patients.

Because these lesions are often found incidentally and frequently in younger people, the additional implication of this recommendation is that we can reduce and avoid both unnecessary imaging and, in the case of CT scanning, unnecessary radiation exposure in this patient population.

Medscape: You mentioned the exception to this recommendation being hepatocellular adenoma.

Dr Merriman: Yes; this recommendation does not apply to those with hepatocellular adenoma. Patients with radiologic evidence of hepatocellular adenoma may have a risk of the lesion potentially transforming into a more neoplastic variant. These patients are typically monitored more closely, often depending in part upon the size of the lesion. However, it is important to remember that this represents a very small proportion of the total number of benign focal liver lesions.

Medscape: Your fifth recommendation is: Don't routinely transfuse fresh frozen plasma (FFP) and platelets prior to abdominal paracentesis or endoscopic variceal band ligation.

Dr Merriman: This recommendation stems from the common practice of attempting to correct coagulopathies often present in patients with cirrhosis such as an elevated international normalized ratio (INR) or thrombocytopenia for procedures such as paracentesis or endoscopic variceal band ligation. Recently, it has been acknowledged that these routine tests of coagulation do not accurately reflect the bleeding risk in patients with cirrhosis. Indeed, bleeding complications associated with these procedures are very rare. So we strongly encourage patients to discuss with their physicians whether routine transfusion of FFP and/or platelets in patients with an elevated INR or thrombocytopenia is indicated for these procedures. This recommendation has the potential to reduce the unnecessary transfusion of finite and costly blood product resources.

Medscape: Is the AASLD planning to add any further recommendations beyond these first "five things"?

Dr Merriman: The AASLD, in both its stewardship and leadership capacity, would definitely be enthusiastic about adding to this first "five things" list. This, in part, also reflects the transformational changes occurring in therapeutics for such very common liver diseases as hepatitis C and nonalcoholic fatty liver disease. Those changes bring about the possibility of further optimizing the delivery of healthcare in a manner that is responsible from both the patient and the societal perspective.

Medscape: How do you see these recommendations affecting both clinicians and patients?

Dr Merriman: These recommendations really address two audiences: patients and physicians. It prompts both parties to discuss testing and treatment and to make informed and prudent decisions about the most appropriate care based upon the patient's individual clinical condition. So, in many ways, it spurs a discussion about what is clinically and medically appropriate and necessary. Conversations about the overuse of medical tests or about procedures that have little benefit (and in some cases may be harmful) are very relevant to both parties.

The Choosing Wisely campaign is an educational process and has the potential to revise and reshape both patient expectations and physician practice patterns in a beneficial way.

Finally, the broad acceptance of the Choosing Wisely campaign and the AASLD list reflects and reinforces the belief that the AASLD and physicians are responsible leaders in healthcare reform.

Medscape: Since this list was released, have you seen a change in clinical practice, or is it too soon to tell?

Dr Merriman: While formal data are not available, the positive response from patients and colleagues has been highly encouraging. I have witnessed the Choosing Wisely list posted prominently in clinics and have personally referred to it when patients have questions about topics addressed. Just last week, for example, a patient who had hepatitis C but who is not going to be treated any time soon wanted a viral load checked. I was able to point to the recommendation on the Choosing Wisely list. That initiated a conversation ultimately recommending against such testing, based upon the Choosing Wisely data and emanating from a credible and responsible organization. In that way, this list can evolve into a powerful tool in educating patients about good healthcare practices.

Source

New HCV Drugs Pass Muster in Real World

Published: Nov 10, 2014

By Michael Smith, North American Correspondent, MedPage Today

BOSTON -- Clinical trials for some of the new direct-acting agents against hepatitis C (HCV) have yielded some impressive efficacy numbers. But how well do the drugs stack up in the real world?

Pretty well, according to studies presented here at the American Association for the Study of Liver Diseases annual meeting.

"Real world data are generally consistent with phase II and II trial data," concluded Donald Jensen, MD, of the University of Chicago Medical Center.

Cure rates are "comparable to rates reported in clinical trials," said Douglas Dieterich, MD, of Mount Sinai Hospital in New York City.

The two presented back-to-back analyses of separate cohorts of patients treated over the past year with regimens containing sofosbuvir (Sovaldi) including the off-label (at the time) combination of sofosbuvir and simeprevir (Olysio).

Jensen discussed data collected by the HCV-Target consortium of academic and community medical centers in North America and Europe, which has been collecting information on 2,063 patients treated with sofosbuvir-containing regimens since mid-April.

They include 384 who started on a regimen of sofosbuvir combined with pegylated interferon and ribavirin, the regimen approved by the FDA for patients with HCV genotypes 1 and 4, and 667 who were treated with sofosbuvir and ribavirin, the regimen approved for patients with genotypes 2 and 3.

The cohort also includes 784 patients who were treated with sofosbuvir and simeprevir, which was only approved (for genotype 1 patients ) last month, and 228 who got those two drugs plus ribavirin.

Since treatment durations vary, Jensen presented data on the so-called SVR₄ -- an absence of detectable HCV RNA 4 weeks after the end of treatment. HCV is regarded as cured when there is no detectable RNA 12 weeks after the end of therapy, the SVR₁₂.

But, Jensen said, among those who have reached the 12-week mark, the positive predictive value of SVR₄ for SVR₁₂ was between 94.4% and 98.2%, while the negative predictive value was 100% across all regimens.

The bottom line, he reported, was that SVR₄ rates were:

• 85% for sofosbuvir with interferon and ribavirin in genotype 1 patients.
• 90% for sofosbuvir plus ribavirin in genotype 2 patients.
• 89% for genotype 1 patients getting sofosbuvir and simeprevir, with or without ribavirin.

Interestingly, he said, the use of ribavirin produces no difference in outcomes across various subcategories of patients with genotype 1 treated with sofosbuvir and simeprevir.

The results in sofosbuvir/simeprevir patients are extremely good, considering that many of the patients would not have been eligible for the pivotal COSMOS trial that led to approval of the combination, commented Mark Sulkowski, MD, of Johns Hopkins University, who was one of the investigators on that study.

For instance, he said, 60% of patients in the HCV-Target cohort were cirrhotic, while COSMOS had a much smaller number of patients with cirrhosis and were generally healthier than those in the HCV-Target cohort.

"You've got a clinical trial, in this case COSMOS, and now you've got the translation into a large number of very sick patients with hepatitis C," he told MedPage Today, "and it shows that these drugs do work very well in real-world clinical practice."

Sulkowski presented a separate, more detailed analysis of the sofosbuvir/simeprevir patients in the HCV-Target group.

Meanwhile, Dieterich said, much the same results came out of analysis of 955 patients whose data was obtained from electronic records in the TRIO network of pharmacies.

His analysis included 822 patients intended to be treated for 12 weeks with the same regimens as the HCV-Target cohort, which had some longer treatment periods.

Among the 822, Dieterich said, the overall SVR₁₂ was 79%, but the group included 79 people who dropped out. The SVR12 among those who completed treatment -- the per-protocol cohort of 743 patients -- was 88%.

The rates are "remarkably high, considering the real-life heterogeneous population here," Dieterich said.

Broken down by genotype and regimen, the intent-to-treat SVR₁₂s were: For sofosbuvir, interferon, and ribavirin 72% in genotype 1 and 67% in genotypes 4, 5, and 6 combined; for sofosbuvir plus ribavirin 50% for genotype 1 and 84% for genotype 2, and for sofosbuvir and simeprevir, plus or minus ribavirin 82% for genotype 1.

The most important predictor of response was cirrhosis, Dieterich said.

Both researchers said the drugs under study were generally well tolerated, with no new safety signals.

The HCV-Target consortium is sponsored by Genentech, Kadmon, Janssen, Merck, Vertex, AbbVie, Bristol Myers Squibb, Gilead, and GSK. Jensen disclosed relevant relationships with AbbVie, Boehringer, Bristol Myers Squibb, GSK, and Janssen.

Dieterich disclosed relevant relationships with AbbVie, Achillion, Bristol-Myers Squibb, Gilead Sciences, Idenix Pharmaceuticals, Merck, and Janssen Therapeutics. He did not report support for his study.

Sulkowski disclosed relevant relationships with Merck, AbbVie, Idenix, Janssen, Gilead, BMS, Pfizer, BIPI, and Vertex.

Primary source: American Association for the Study of Liver Diseases
Source reference: Dieterich D, et al "Evaluation of sofosbuvir and simeprevir-based regimens in the TRIO network" AASLD 2014; Abstract 46.

Additional source: American Association for the Study of Liver Diseases
Source reference:Jensen DM, et al "Safety and efficacy of sofosbuvir-containing regimens for hepatitis C: Real-world experience in a diverse, longitudinal observational cohort" AASLD 2014; Abstract 45.

Source

How Gilead and Price Controls Played a Supporting Role in the Midterms

By Chris Versace

Published November 10, 2014 FOXBusiness

The defeat of more than a half dozen sitting Democratic senators last Tuesday marks the first time since 1980 that the GOP has been able to unseat more than two incumbents in a single night.

As political consultants and opinion leaders look for what caused the shellacking Democrats took at the polls, a number of answers stand out: The lack of quality job creation, stagnant wages, a mixed at best foreign policy and other would be initiatives. But let’s not forget that consumers tend vote with their wallets and from there we have to consider the impact of ObamaCare. According to a Wall Street Journal review of proposed 2015 insurance rates in the 10 states that have completed their filings, in all but one of them, the largest health insurer in the state is proposing to increase premiums between 8.5% and 22.8% for next year.

Taking a look back, since 2010, when the president's health care proposal was passed by a strict party line vote, 28 U.S. Senators have either lost their election, retired or died. One more seems destined to join the list, Sen. Mary Landrieu, (D-LA), when her runoff election is completed in December. Those numbers are truly historic and give credence to the damage the law has done to the Democratic Party. Detractors warned the law would lead to price increases in health care premiums, shortages of doctors, price controls and ultimately, rationing of care.  The warnings on price controls have begun to take root.

Commenting on its September quarter earnings, health care company Humana said investments in ObamaCare health care exchanges and state-based contracts as well as increased costs related to a new hepatitis C treatment weighed on the company’s earnings. According to the Centers for Disease Control hepatitis C can cause cancer or cirrhosis of the liver, affects 3.2 million Americans and kills 15,000 a year. One of the vendors of that new hepatitis C treatment is biopharmaceutical company Gilead Sciences (GILD) with its new drug Sovaldi. To date, 117,000 patients have been treated with Sovaldi, which shows that the drug has received amazing reception despite some concerns about the pricing.

Controversy surrounding high-cost drugs is nothing new and it has been around for years. After the Food and Drug Administration approved Sovaldi, which can cure hepatitis C, but costs about $1,000 a pill, the controversy was reignited. Basic economics dictates that if investors cannot recoup their investments, they will shift their dollars into other fields and areas.  Bringing a drug to market, thanks in part of the red tape imposed by the government itself is costly -- according to the Tufts Center for the Study of Drug Development the total cost of bringing a new drug to market is now $1.2 billion due in part to regulatory compliance and litigation expenses.

Health insurance companies were already bristling over the cost of Gilead's $84,000 hepatitis C cure Sovaldi and are going apoplectic over the company's next-generation version, Harvoni, which is priced at $94,500.  Because the new version replaces multiple companion drugs that are no longer required Gilead’s pitch is the new drug is actually less expensive. Sovaldi is often combined with other treatments bringing the total cost closer to $150,000 per patient.

Rather than the industry players settling the issue through negotiation, health plans are turning to Congress to step in and arbitrarily limit prices, which could undermine the investment that is critical to developing new cures. It should come as no surprise that three members of the House Energy and Commerce Committee dispatched a letter to the chairman demanding that Gilead’s executives be hauled before the committee to justify their pricing.

This past May, The National Coalition on Health Care (NCHC) launched the ‘Campaign for Sustainable Rx Pricing’ and has inserted itself in the national debate about drug pricing. Looking at the coalition’s membership -- 85 organizations includes major businesses, labor unions, insurers, providers, state based benefit programs, and consumers -- as well as the President and CEO John Rother’s background -- long time EVP for Policy, Strategy, and International Affairs at AARP -- it comes as little surprise it is calling for government intervention to control the price of the drug.

The argument for price controls fails every reliable economic theory in the book. Ten years ago, the late-Milton Friedman joined over 150 of his peers in arguing against them. In their words, “Drug price controls are more difficult to remove than other price controls. Controls on oil and other products often tend to be limited or short-lived, as voters eventually object to the resulting shortages and distortions. The effects of drug price controls, however, are far more difficult to observe because they mainly affect medicines that haven’t been invented yet."

When innovators are on the cusp of major advances in cancer, diabetes, HIV/AIDS and hepatitis C, among others, arbitrarily limiting the economic rewards and incentives for a major breakthrough make it more difficult to raise capital, stunt innovation, and hurt patients who rely on new advances. While Sovaldi costs upwards of $150,000 when bundled with other drugs, that pales in comparison to the costs associated with not treating hepatitis C. In other words, a cure, even an expensive one, for hepatitis C is far less costly than ongoing treatment. If a company can not recoup on its investment efforts across its entire product portfolio and generate a profit while doing so in order to benefit its shareholders then few companies would be willing or able to develop potentially break through products, particularly in the health care industry.

Remember too, the principal advocate for price controls -- the NCHC -- represents labor unions, insurers and other benefit program providers and is funded in part by the health insurance industry’s trade association, America’s Health Insurance Plans (AHIP), the Pharmaceutical Care Management Association, and the American Hospital Association. To say they might have a vested interest in price controls is more likely than not.

From a policy standpoint, the most important thing for health policy to accomplish is to get the incentives right for new cures to be developed and made available to improve and extend people’s lives.  That should mean stream lining regulation as well as fostering competition and choice.  Price controls would do the exact opposite, and Congress should reject the rent-seekers calling for them to get involved in a pricing dispute between industry players who are perfectly capable of negotiating for themselves.

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Good Old Aspirin Might Protect Against Liver Fibrosis

Medscape Medical News > Conference News

Neil Osterweil
November 10, 2014

BOSTON — Will wonder drugs never cease? Aspirin, already touted for its cardiovascular and anti-inflammatory prowess, seems to be flexing its muscles against liver fibrosis, particularly in people at risk for chronic liver disease, according to new research.

"Clinical equipoise is emerging that may justify prospective randomized trials of aspirin and, potentially, other antiplatelet drugs such as antifibrotic agents," Gordon Jiang, MD, a gastroenterology fellow at the Beth Israel Deaconess Medical Center in Boston, and colleagues state in a scientific poster here at The Liver Meeting 2014.

In a population-based cross-sectional study of more than 14,000 adults, there was "a consistent association between aspirin use and less liver fibrosis," Dr. Jiang and colleagues report.

The team drew on the National Health and Nutrition Examination Survey (NHANES) III to look at the association between aspirin, ibuprofen, and liver fibrosis. Fibrosis was measured with four validated noninvasive indices: Fibrosis-4, the nonalcoholic fatty liver disease fibrosis score, the aspartate aminotransferase/platelet ratio index, and the Forns Index.

To see if the association between aspirin and fibrosis protection is stronger in patients most at risk for fibrosis, they did additional analyses in patients with viral hepatitis, heavy drinkers, and patients with fatty liver disease.

On the four measures, the use of aspirin was consistently associated with lower stages of liver fibrosis. In contrast, there was virtually no link between ibuprofen use and liver fibrosis.

Similarly, in an analysis of patients with and without chronic liver disease (hepatitis B or C infection, more than 5 alcoholic drinks per day, or suspected nonalcoholic steatohepatitis), aspirin but not ibuprofen was consistently associated with lower stages of fibrosis.

For patients with or at risk for liver disease, compared with those without risk factors, there was about a 5-fold increase in the negative coefficient for the interaction between aspirin use and liver fibrosis. This suggests that the protective effect of aspirin is much larger in patients with chronic liver disease, said researcher Yury Popov, MD, PhD, assistant professor of medicine at the Beth Israel Deaconess Medical Center.

The researchers acknowledge that the study was limited by the observational design, and by that fact that the NHANES III data were limited to 1 month of drug use, "whereas the protection against liver fibrosis likely requires long-term use."

They speculate that the antiplatelet activity of aspirin, rather than its anti-inflammatory properties, likely account for its positive effects on fibrosis.

"Our observations support emerging experimental and clinical evidence for a pathologic link between platelet activation and liver fibrosis," they write.

In a separate study, also presented here, another group of researchers report that "platelets drive liver fibrosis through the direct activation of hepatic stellate cells in chronically injured liver."

"We also found that aspirin in the long term, at the low dose — the antiplatelet dose — is reducing — well actually, preventing — fibrosis in the mouse model," Dr. Popov, who was involved in both studies, told Medscape Medical News.

More potent antiplatelet agents — such as clopidogrel (Plavix), prasugrel (Effient), and others currently in the pipeline — could have an even stronger effect against fibrosis, said Athan Kuliopulos, MD, PhD, professor of medicine at the Tufts University Sackler School of Biomedical Sciences in Boston, who was not involved with the study.

"And this is just liver fibrosis," he told Medscape Medical News. "What does it mean for outcome?"

He said that if, as he and his colleagues theorize, platelet activation or action is a primary cause of fibrosis, it might be possible to "bypass the platelet entirely," and target the factor Xa protease.

Dr. Jiang has disclosed no relevant financial relationships. Dr. Popov reports consulting for and receiving research grants from Gilead Sciences. Dr. Kuliopulos is the CEO of Oasis Pharmaceuticals.

The Liver Meeting 2014: American Association for the Study of Liver Diseases (AASLD). Abstract 449, presented November 8, 2014; abstract 778, presented November 9, 2014.

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Preop Factors Affect CVD Risk After Liver Transplantation

Medscape Medical News > Conference News

Neil Osterweil
November 09, 2014

BOSTON — A review of data on nearly 33,000 liver transplant recipients suggests that some modifiable pretransplant risk factors can account for major adverse cardiovascular events in the first 3 months after surgery.

"What was most interesting to us was that the thromboembolic diseases, which we tend to screen for very closely — pulmonary embolism, myocardial infarction — only accounted for about 7% to 10% of all cases of cardiovascular complications," Lisa VanWagner, MD, a gastroenterology and hepatology fellow at the Northwestern University Feinberg School of Medicine in Chicago.

Before transplantation, "we rigorously evaluate our candidates cardiovascularly, but we focus on coronary disease in our risk stratification, so patients get stress echocardiograms and coronary catheterization. What we tend to forget about are these subclinical changes, that idea of cirrhotic cardiomyopathy, the arrhythmic potential, and the chronotropic incompetence that happens in cirrhosis of the heart, which is the inability to mount a response to stress," she told Medscape Medical News.

Cardiovascular events — including myocardial infarction, heart failure, pulmonary embolism, atrial fibrillation, cardiac arrest, and stroke — are among the leading causes of complications after transplantation, and are associated with worse overall survival in the first year after transplantation.

Dr VanWagner and colleagues created a database to assess the prevalence and predictors of major adverse cardiovascular events in the first few months after transplantation.

They did so by identifying adults who underwent a primary liver transplant from February 2002 to December 2012 in a member institution of the University Health System Consortium, and matching them to recipients in the Organ Procurement and Transplantation Network registry. They used billing codes to assess comorbidities and the incidence of 30- and 90-day major cardiovascular events.

Of the 32,810 patients they identified, 4400 were admitted to a hospital within 30 days of transplantation, and 6095 were admitted within 90 days. Of the patients admitted in the first month, 330 (7.4%) had a major adverse cardiovascular event; of those admitted in the first 3 months, 429 (7.0%) had a major adverse cardiovascular event.

The most common causes of 30- and 90-day adverse events were atrial fibrillation, heart failure, and pulmonary embolism.

Patients who experienced a major adverse cardiovascular event were significantly more likely than other recipients to have alcoholic liver disease or nonalcoholic steatohepatitis as the primary indication for transplantation (P = .0003). They were also more likely to have a higher mean calculated Model for End-Stage Liver Disease score (P = .001), and to have a cardiovascular comorbidity present at the time of transplantation. Significant cardiovascular comorbidities were heart failure (P < .0001), ischemic heart disease (P < .0001), hypertension (P = .05), stroke (P = .001), and atrial fibrillation (P < .0001).

Other significant comorbidities were chronic kidney disease, hepatopulmonary syndrome, and asthma or chronic obstructive pulmonary disease.

On multivariate regression analysis, factors that independently predicted any major adverse cardiovascular event within 90 days included age older than 45 years (incidence rate ratio [IRR], 1.8; 95% confidence interval [CI], 1.2 - 2.7), alcoholic cirrhosis (IRR, 1.6; 95% CI, 1.2 - 2.2), nonalcoholic steatohepatitis (IRR, 1.6; 95% CI, 1.2 - 2.2), a high pretransplant level of creatinine (IRR, 1.1; 95% CI, 1.04 - 1.2), atrial fibrillation (IRR, 6.9; 95% CI, 4.9 - 9.6), and stroke (IRR, 6.3; 95% CI, 1.6 - 25.4).

Major adverse cardiovascular events were also associated with significantly worse 1-year survival (75.2% vs 85.6%; P < .0001).

These findings suggest an opportunity to improve care for liver transplant candidates and enhance recipient selection, said Dr VanWagner.

Certainly alcohol damages the liver, but it also damages the heart.

A gastroenterologist who was not involved in the study told Medscape Medical News that cardiovascular complications are a major problem and have a serious effect on outcomes in patients undergoing liver transplantation.

The investigators "have done a wonderful job looking at risk predictors of complications and describing the major problems that are occurring in the early days after transplantation," said Simon Robson, MD, chief of the division of gastroenterology at Beth Israel Deaconess Medical Center and professor of medicine at Harvard Medical School, both in Boston.

Dr Robson said that the associations the investigators found between postoperative cardiovascular risk and fatty liver disease and alcoholic cirrhosis are particularly important.

"With hepatitis C being eradicated, most of the patients we're going to be transplanting in the next two decades fall into these categories, and in Europe, most of the patients are alcoholic right now. Certainly alcohol damages the liver, but it also damages the heart," he said.

The study was supported by the National Heart, Lung, and Blood Institute; the American Liver Foundation; and the AASLD Foundation. Dr VanWagner and Dr Robson have disclosed no relevant financial relationships.

The Liver Meeting 2014: American Association for the Study of Liver Diseases (AASLD). Abstract 549. Presented November 8, 2014.

Source

New pill that can cure hepatitis C approved for patients in Scotland

STV
10 November 2014 14:00 GMT

A treatment that can cure the hepatitis C disease has been approved for use in Scotland.

The disease now affects one in every 100 people in Scotland and causes over 20% of all liver transplants.

The decision means some of the sickest patients can access a new regimen that is a daily pill, taken without some existing toxic drugs.

The pill, which is called daclatasvir, has a cure rate of around 98% in a majority of patients.

Daclatasvir is an oral once-daily pill, used in combination with other medicinal products, to treat adult patients with chronic hepatitis C.

In published clinical studies it has shown potential to offer cure in a high number of patients.

The decision makes Scotland the first country in Europe to adopt positive guidance for daclatasvir and means it will be routinely available to eligible patients through the Scottish NHS.

Approximately 50,000 people in Scotland are infected with hep C, which can cause liver cancer or liver failure.

This is equivalent to around one per cent of the Scottish population.

Dr. Stephen Barclay, liver consultant at the Glasgow Royal Infirmary said: "This decision is an important milestone for around 40,000 patients in Scotland with chronic hepatitis C, who live with the risk of cirrhosis, liver failure and liver cancer.

"Whilst the standard of care for hepatitis C in Scotland is exemplary, there remain patients for whom current treatments have been unsuitable or ineffective.

"The acceptance of daclatasvir offers a new option that can provide high rates of viral cure and thus bring real benefits for patients who require treatment."

Bob Leary, 67, who lives near Edinburgh, contracted hep C in 1986 through a blood transfusion.

Since then it has destroyed his liver; he's had one transplant but hasn't had the virus cured so it's still damaging his new liver.

He's too ill to take existing treatment options and is a perfect example of what hep C can do to you and how these treatments will make a big difference to Scottish patients.

Source

HCV Combo Effective After Liver Transplant

Published: Nov 10, 2014

By Michael Smith, North American Correspondent, MedPage Today

Action Points

• Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

BOSTON -- A two-drug combination for hepatitis C (HCV) appeared to be curative in more than 90% of liver transplant recipients, a researcher said here.

HCV recurs in all transplant patients and can lead quickly to cirrhosis and loss of the graft, according to Surakit Pungpapong, MD, of the Mayo Clinic in Jacksonville, Fla.

But in preliminary results from a three-center case series, the combination of simeprevir (Olysio) and sofosbuvir (Sovaldi) for 12 weeks led to cures in most patients with complete data, Pungpapong reported in a plenary session of the American Association for the Study of Liver Diseases annual meeting.

The combination was recently approved to treat HCV, but was off-label during the study, Pungpapong said.

But the "million-dollar question" is how accessible the combination is, given high prices for both drugs, commented Susan Orloff, MD, of the Oregon Health & Science University in Portland, who was not involved in the study but who co-moderated the plenary session at which it was presented.

The outcomes, she told MedPage Today after the session, are "fantastic" -- much better than the 30% to 35% seen with earlier regimens.

But "the major issue with all of the direct-acting agents is they are very expensive and insurance companies are not covering these for our patients," she said. "Physicians have to appeal, appeal again, and appeal a third time ... It's a huge process."

Indeed, she said, the use of the combination earlier in the disease course might prevent the need for transplant, saving $200,000 or so for the procedure itself and also about $10,000 a year for immune suppression.

"If we could give more patients these drugs, these direct-acting antivirals, then we would obviate the need for transplant," she said.

Gilead, the maker of sofosbuvir, famously set the wholesale acquisition price at $84,000 for a 12-week course of treatment -- or about $1 per pill -- while the price set by Janssen for simeprevir is somewhat lower, at $66,000 for 12 weeks of therapy.

The study population -- from the three Mayo Clinics in Jacksonville, Scottsdale, Ariz., and Minneapolis -- included 109 patients with histologic evidence that their genotype 1 HCV had returned after the transplant.

Of those, 101 have finished treatment, 90 are at least 4 weeks from the end of treatment, and 66 are 12 weeks or more after the end of therapy.

Treatment began at a median of 29 months after transplant and most of the patients had failed at least one previous course of therapy. About a quarter of the patients were also given ribavirin, a nonspecific antiviral drug that used to be a mainstay of HCV treatment.

The primary endpoint of the study is an absence of detectable HCV RNA 12 weeks after the end of treatment, the so-called SVR₁₂, which is regarded as a cure because few people relapse after that point.

However, having undetectable HCV 4 weeks after the end of treatment -- an SVR₄ -- is regarded as highly predictive of SVR₁₂.

In an intention-to-treat analysis, 99 of 101 patients (98%) had undetectable HCV RNA at the end of treatment. The remaining two included a patient who suffered a drug-induced lung injury and later died and one who stopped treatment after a viral rebound in week six of therapy.

Also, 83 of 90 patients have reached an SVR₄ and 60 of 66 have reached SVR₁₂, 92% and 91% respectively.

The addition of ribavirin to the direct-acting combination for 24 patients had no significant affect on the outcomes, Pungpapong said.

On the other hand, the degree of fibrosis did matter: 96% of patients with Metavir score F0 through F2 achieved SVR₁₂, compared with 76% of those with Metavir F3 or F4, for a difference that was significant (P=0.03).

The difference was accentuated among patients with genotype 1a disease, Pungpapong said.

Most adverse events were mild, and included fatigue in 9%, hyperbilirubinemia in 5%, and nausea and headache in 4% each. Among patients getting ribavirin, 42% developed anemia (a recognized side effect of the drug) compared with 2% of the remaining patients.

There were only two serious adverse events -- the lung injury case and a patient who developed pancreatitis and had to stop the HCV therapy for 2 weeks. The patient restarted the medications and achieved SVR₁₂.

Pungpapong disclosed relevant relationships with Bristol Myers Squibb (BMS) and Gilead. One co-author disclosed relevant relationships with Eisai, Merck, Gilead, Idenix, BMS, Novartis, Vertex, Janssen, Ikaria, and AbbVie.

Other co-authors disclosed no relevant relationships with industry.

Orloff disclosed no relevant relationships with industry.

Primary source: American Association for the Study of Liver Diseases
Source reference: Pungpapong S, et al "Multicenter experience using sofosbuvir and simeprevir with/without ribavirin to treat HCV genotype 1 after liver transplantation" AASLD 2014; Abstract 9.

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Advantages of Gilead’s Harvoni over emerging hepatitis C treatments

10-11-2014

US surveyed specialists anticipate prescribing Gilead Sciences’ (Nasdaq: GILD) Harvoni to a high proportion of their genotype-1 infected hepatitis C virus (HCV) patients, including those with cirrhosis of the liver, even if it is listed on a non-preferred formulary tier (tier 3 or higher).

Harvoni, a fixed-dose combination of Gilead’s nucleotide polymerase inhibitor sofosbuvir and NS5A inhibitor ledipasvir, is the first once-daily single tablet regimen for HCV infections. According to physicians surveyed for a news report from Decision Resources Group, Harvoni has advantages over other emerging treatment options on all efficacy, treatment duration, safety and tolerability attributes considered.

Surveyed MCOs have prioritized Sovaldi over Olysio

Furthermore, surveyed Managed Care Organization (MCO) pharmacy and medical directors have prioritized formulary inclusion of Gilead’s Sovaldi over (sofosbuvir) Janssen/Medivir’s Olysio (simeprevir), suggesting that Sovaldi’s broad label and excellent clinical profile have allowed it to defend its higher cost.

Other key findings from the US Physician & Payer Forum report, titled Hepatitis C Virus: How will More Efficacious Direct-Acting Antivirals Influence US Prescribing and Reimbursement for this Dynamic Indication, include:

• Impact of new HCV treatment guidelines on MCO reimbursement: Among the almost two-thirds of surveyed MCO pharmacy and medical directors who are aware of the American Association for the Study of Liver Diseases’ treatment guidelines, more than two-thirds are aware of recommended treatments, and some indicated reducing formulary restrictions and streamlining prior authorization approvals for prescribed regimens recommended in the guidelines. These findings underscore the critical importance of treatment guidelines in favorable positioning of HCV therapies for reimbursement by MCOs.
• Concerns over increased risk of relapse following shortened course of therapy: Food and Drug Administration labeling recommends an eight-week course of Harvoni in treatment-naive, non-cirrhotic patients with lower baseline viral loads. Strikingly, nearly half of surveyed experts are concerned that short treatment duration increases risk of viral relapse following completion of HCV therapy with a high proportion indicating that durations of eight weeks or less are too short.

Decision Resources Group analyst Seamus Levine-Wilkinson commented: “Physicians report that discontinuation rates for Sovaldi and/or Olysio are higher than expected from clinical trials. Notably, the elevated “real world” discontinuation rates do not appear to stem from low efficacy or unexpected safety issues but are rather driven by high out-of-pocket cost associated with these therapies. Our findings may also have implications for the recently launched Harvoni as well as other novel therapies expected to enter the market in the near future. Approximately four out of five surveyed physicians have either already contacted or plan to reach out to patients regarding the newest HCV treatment options. As a result, uptake of novel HCV agents could surge as physicians treat the sizeable number of warehoused patients.”

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Galectin Therapeutics' Phase 1 Data Presented at AASLD Annual Meeting Advances GR-MD-02 Into Phase 2 Clinical Development

NORCROSS, Ga., Nov. 9, 2014 (GLOBE NEWSWIRE) -- Galectin Therapeutics Inc. (Nasdaq:GALT), the leading developer of therapeutics that target galectin proteins to treat fibrosis and cancer, presented data today from the Company's Phase 1 clinical trial of GR-MD-02 in NASH (fatty liver disease) patients with advanced fibrosis at The Liver Meeting in Boston, Massachusetts. Stephen A. Harrison, MD, Chief of Hepatology at Brooke Army Medical Center in Fort Sam Houston and a clinical trial investigator in Galectin Therapeutics' Phase 1 clinical trial, shared the data during an oral presentation at the 65^th Annual Meeting of the American Association for the Study of Liver Diseases.

The Phase 1 first-in-man study evaluated the safety, tolerability, and drug pharmacokinetics for single and multiple doses of galectin-inhibiting drug GR-MD-02 when administered to patients with NASH (fatty liver disease) with advanced fibrosis. Additionally, exploratory serum biomarkers were evaluated as potential tools that may be used to aid in future studies. Dr. Harrison reviewed previously-reported results from the ongoing Phase 1 clinical trial including completed cohorts 1 and 2 and also presented, for the first time, interim data from completed patients from cohort 3. In the three-cohort design, eight patients (6 active drug and 2 placebo) completed cohort 1 at the 2 mg/kg dosage; nine patients (7 active drug and 2 placebo) completed cohort 2 at the 4 mg/kg dosage; and nine patients (6 active drug and 3 placebo) have so far completed cohort 3 at the 8 mg/kg dosage. Therefore, there was a similar number of patients from each of the cohorts for comparison purposes.

Overall, data from the multi-center, partially blinded Phase 1 trial showed that administration of 2, 4 and 8 mg/kg lean body weight of GR-MD-02 intravenously for four doses over 6 weeks was safe and well tolerated. Thus, the primary endpoint of the study has been met. There were no serious adverse events reported in any of the three cohorts and mild (grade 1) adverse events possibly related to study drug were found in 3 placebo patients and only 2 patients receiving active drug.

In cohorts 1 and 2, pharmacokinetic data demonstrated a proportional increase in total drug exposure with doubling of the dose of GR-MD-02 with no accumulation after four doses. In newly released data from cohort 3, Dr. Harrison reported that pharmacokinetic analysis of GR-MD-02 plasma levels for the 8 mg/kg dose provides drug coverage in the upper portion of the targeted therapeutic range derived from NASH animal model studies.

An evaluation of exploratory serum biomarkers in all three cohorts revealed that the vast majority of biomarkers do not seem to be useful tools to aid in the design of short-term therapeutic trials. These exploratory biomarkers showed marked variability over time in placebo patients as well as active drug patients.

In contrast to other biomarkers, FibroTest^®, a composite score that has been correlated with the extent of liver fibrosis, was significantly reduced by GR-MD-02 treatment in cohort 3. The treatment effect on FibroTest score was due to a statistically significant reduction of alpha-2 macroglobulin, one of the components of the score. This reduction in FibroTest score and alpha-2 macroglobulin was only seen in the high dose cohort 3 and not in cohort 1 and 2.

According to Dr. Harrison, "Today's presentation to the scientific community at AASLD reveals key insight into the safe use of GR-MD-02 on fatty liver disease in advanced fibrosis. The objective of the Phase 1 trial is to evaluate safety and pharmacokinetics of GR-MD-02. What we have seen so far in the Phase 1 trial is that GR-MD-02 is safe and well tolerated at multiple doses. It was an added bonus that we found a reduction for serum biomarker alpha-2 macroglobulin."

"The company is planning to initiate a Phase 2 clinical trial in the second quarter of 2015 based on the robust pre-clinical effects of the drug and these successful Phase 1 results," said Peter G. Traber, M.D., Chief Executive Officer, President and Chief Medical Officer of Galectin Therapeutics. "Following a recent meeting with the U.S. Food and Drug Administration, the company has determined its Phase 2 trial will be in NASH patients with cirrhosis with evaluation of portal hypertension (hepatic venous pressure gradient) as the primary surrogate endpoint and the amount of collagen, as determined by digital morphometric analysis, as a key secondary endpoint. Additional non-invasive measures of liver function and structure will also be assessed. Further details of the Phase 2 clinical trial will be announced prior to initiation. Given the positive results reviewed at AASLD today, cohort 3 of the Phase 1 trial will be ended after the completion of an additional four patients that have been enrolled (13 patients total in cohort 3)."

Dr. Traber added, "I want to sincerely thank three groups for their involvement in this study. First, and most importantly, I thank the individual patients who donated their time and effort to help advance a promising therapy—their contribution was critical to the Company's progress in development of GR-MD-02. Second, I thank the world-class group of investigators and their support groups who worked on this trial. Finally, CTI as our CRO partner worked tirelessly to accomplish the results."

GR-MD-02 is Galectin Therapeutics' patented, proprietary molecule derived from apple pectin material that binds to and inhibits galectin proteins, predominantly galectin-3. 

About Fatty Liver Disease with Advanced Fibrosis

Non-alcoholic steatohepatitis (NASH), also known as fatty liver disease, has become a common disease of the liver with the rise in obesity rates, estimated to affect nine to 15 million people, including children, in the U.S. Fatty liver disease is characterized by the presence of fat in the liver along with inflammation and damage in people who drink little or no alcohol. Over time, patients with fatty liver disease can develop fibrosis, or scarring of the liver, and it is estimated that as many as three million individuals will develop cirrhosis, a severe liver disease where liver transplantation is the only current treatment available. Approximately 6,300 liver transplants are done on an annual basis in the U.S. There are no drug therapies approved for the treatment of liver fibrosis.

About Galectin Therapeutics

Galectin Therapeutics (Nasdaq:GALT) is developing promising carbohydrate-based therapies for the treatment of fibrotic liver disease and cancer based on the Company's unique understanding of galectin proteins, key mediators of biologic function. We are leveraging extensive scientific and development expertise as well as established relationships with external sources to achieve cost effective and efficient development. We are pursuing a clear development pathway to clinical enhancement and commercialization for our lead compounds in liver fibrosis and cancer. Additional information is available at www.galectintherapeutics.com.

Forward Looking Statements

This press release contains, in addition to historical information, forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements relate to future events or future financial performance, and use words such as "may," "estimate," "could," "expect" and others. They are based on our current expectations and are subject to factors and uncertainties which could cause actual results to differ materially from those described in the statements. These statements include those regarding our plans, expectations and goals regarding clinical trials, including our expectation that a final clinical data report from the third cohort should be available in January 2015, plans regarding design and composition and timing of a Phase 2 clinical trial, and plans regarding future funding alternatives and the sufficiency of cash on hand to fund future operations and planned research and development through mid-2016. Factors that could cause our actual performance to differ materially from those discussed in the forward-looking statements include, among others, that our plans, expectations and goals regarding any clinical trial or any future trials are subject to factors beyond our control and there is no guarantee that we will avoid delays in the development of our drug products or receive FDA approval for any of our drugs in development. Any current clinical trials and any future trials may not produce positive results in a timely fashion, if at all, and any necessary changes during the course of a trial could prove time consuming and costly. We may have difficulty in enrolling candidates for testing, which would impact our estimates regarding timing, and we may not be able to achieve the desired results. Upon receipt of FDA approval, we may face competition with other drugs and treatments that are currently approved or those that are currently in development, which could have an adverse impact on our ability to achieve revenues from any proposed indications. Plans regarding development, approval and marketing of any of our drugs, including GR-MD-02, are subject to change at any time based on the changing needs of our company as determined by management and regulatory agencies. To date, we have incurred operating losses since our inception, and our ability to successfully develop and market drugs may be impacted by our ability to manage costs and finance our continuing operations. For a discussion of additional factors impacting our business, see our Annual Report on Form 10-K for the year ended December 31, 2013, and our subsequent filings with the SEC.  You should not place undue reliance on forward-looking statements. Although subsequent events may cause our views to change, we disclaim any obligation to update forward-looking statements.

Galectin Therapeutics Inc.
Peter G. Traber, MD, 678-620-3186
President, CEO, & CMO

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Very good results of Civacir® (Hepatitis C Immune Globulin) US Phase III clinical trial

Published on Monday, 10 November 2014 09:51

• Preliminary data presented at the Congress of the American Association for the Study of Liver Disease (AASLD) show prevention of re-infection after liver-transplantation
• More than 50% of study patients have been enrolled in the Civacir Phase III trial

DREIEICH, Germany I November 10, 2014 I Biotest AG announced yesterday in an oral presentation the efficacy and safety interim results from its ongoing US Phase III study (Study 988) with Civacir at the Congress of the American Association of the Study of Liver Disease (AASLD) in Boston, Massachusetts, USA.

Biotest Pharmaceuticals Corporation (BPC) (a subsidiary of Biotest AG) is the only manufacturer of an investigational Hepatitis C immune globulin (Civacir®) worldwide. In the ongoing Phase III trial, Civacir® is being investigated in patients who receive a liver transplant due to chronic hepatitis C infection.

End-stage liver disease due to hepatitis C infection is a common indication for liver transplantation. However, newly transplanted livers are rapidly infected by hepatitis C viruses which are still circulating in the patient's body.

Currently, there is no approved treatment available to prevent recurrence of the hepatitis C virus after transplant surgery since current antiviral regimens are generally not used due to toxicities, tolerability issues and drug-drug interactions minimum within the first 6 months after transplantation. Approximately 30% of liver transplant patients require a second liver transplant within 5 years.

This randomized, open-label Phase III trial conducted in 24 clinical centers in the United States is to evaluate the efficacy, safety and pharmacokinetics in the hepatitis C positive transplant population. More than half of the planned patient number has been enrolled in the study.

All patients in the study received antiviral treatment prior to transplantation, including new recently approved virostatics. Patients were randomly assigned to the study drug or the control group. Patients who received the study drug received either 200 mg/kg or 300 mg/kg body weight in the peri- and post transplant periods. The control group received no study drug.

To date, none (0%) of the patients in the higher dosage group have experienced HCV recurrence. Control subjects have a 35% HCV recurrence rate. “The current data are very exciting and we hope that after completion of the study the final evaluation will confirm the presented data”, said Prof Gregor Schulz, CEO of Biotest AG.

The tolerability of tCivacir® was excellent and comparable to the safety profile of other immune globulin products.

About Civacir®

Civacir® is an intravenous immune globulin preparation with high titer of hepatitis C (HVC) antibodies. It is currently being investigated for the prevention of HCV recurrence in patients undergoing liver transplantation. Civacir® is administered during the critical time after liver transplantation, when patients are receiving immunosuppressive therapy and treatment with approved antiviral therapies is not indicated.

SOURCE: Biotest

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New Non-Invasive Technology Diagnoses Fatty Liver Disease

PERTH, Australia, Nov. 10, 2014 /CNW/ - ASX listed Resonance Health (ASX:RHT) officially launched an innovative new diagnostic imaging solution for liver patients worldwide at the American Association for the Study of Liver Diseases annual conference in Boston this week.

HepaFat-Scan technology was developed in collaboration with the University of Western Australia, and uses magnetic resonance imaging (MRI) scanners in a non-invasive manner, to measure the concentration of fat in the human liver.

This is the first and only technology of its kind to obtain regulatory clearances in the USA - FDA, Europe - CE Mark, and Australia - TGA and has also just won the coveted Western Australian Innovation of the Year award at the 2014 WA Innovator of the Year Awards.

Chief Scientist Professor Tim St Pierre said HepaFat-Scan addresses the growing prevalence of fatty liver disease in Australia and many other countries, as well as an unmet need for non-invasive diagnostic tools to diagnose and monitor liver disease.

"It reports volumetric fraction of fat in the liver, a measure that can be directly compared to a volumetric biopsy fat fraction measurement, providing patients and doctors with a more accurate diagnostic tool as part of a structured intervention protocol or clinical research trial."

Compared with the traditional gold standard for clinical assessment of liver fat - histopathological assessment, HepaFat-Scan is a much more objective and non-invasive MRI based method with greater reproducibility and significantly reduced sampling error.

Hence, clinicians and patients can greatly benefit from an accurate HepaFat-Scan measurement of liver fat to monitor and manage efficacy of treatment, and to provide prognoses for fatty liver disease and associated multiple hepatic and systemic disorders and many other related diseases.

All image analysis and reporting services are provided from Resonance Health's ISO 13485 certified Perth based facility and are utilised by hospitals in over 20 countries, and in international clinical trials.

The Innovator of the Year Program is an annual event run by the Western Australian Department of Commerce that fosters a culture of innovation in Western Australia and acknowledges the achievements of WA's leading innovation enterprises.

SOURCE Resonance Health

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Pharco Pharmaceuticals Licenses Clinical Stage Hepatitis C Virus (HCV) NS5A Inhibitor PPI-668 from Presidio Pharmaceuticals

November 10, 2014 07:00 AM Eastern Standard Time

Pharco committed to developing curative therapy for Egyptians with HCV

ALEXANDRIA, Egypt & SAN FRANCISCO--(BUSINESS WIRE)--Pharco and Presidio today announced that they have entered into an exclusive license agreement for Presidio’s HCV NS5A inhibitor PPI-668 for development and commercialization to treat HCV infection in Egypt. This exclusive license includes an opportunity for Pharco to expand its licensed territory to one or more additional countries in the MENA region.

“We look forward to our collaboration with Pharco to provide HCV patients with this highly active inhibitor.”

“This licensing agreement provides Pharco with an opportunity to develop an effective, safe and affordable treatment for Egyptians with HCV infection,” said Dr. Sherine Helmy, BSc, MBA, DBA, Pharco Pharmaceuticals Vice Chairman & Chief Executive Officer. “We believe that PPI-668, in combination with other therapeutic agents offers another potential path to treat and, hopefully, cure patients.”

“PPI-668 is a potent HCV NS5A inhibitor with a favorable pharmacokinetic profile that has shown high SVR rates in combination with other direct acting antiviral agents,” said Richard Colonno, Ph.D., Presidio’s Chief Scientific Officer. “We look forward to our collaboration with Pharco to provide HCV patients with this highly active inhibitor.”

Pharco will fund clinical development and commercialization of PPI-668 in Egypt, and potentially the MENA region. Presidio will receive upfront and development milestone payments, as well as tiered royalties based on product net sales in Egypt and potentially the MENA region. Pharco made an equity investment in Presidio related to the license agreement.

About Pharco Pharmaceuticals

Pharco Pharmaceuticals is the founding member company of Pharco Corporation, founded by Dr. Hassan Abbas Helmy and started operations in 1987. Pharco Corporation is a group of nine health care companies operating in the pharmaceutical field for development, manufacturing, marketing, distributing and exporting a comprehensive array of branded and generic drugs, along with an increasing number of licensed pharmaceutical products. Today Pharco employs over 8,000 employees, and has over 500M product sales units—ranking as the leader in the Egyptian pharmaceutical market, with 13.2% market share in 2013. Pharco also exports to 47 countries around the world. Pharco works towards one goal…to provide highly effective, safe pharmaceutical products to patients at an affordable price.

About Presidio

Presidio Pharmaceuticals, Inc. is a San Francisco-based clinical-stage pharmaceutical company dedicated to the discovery and development of small-molecule antiviral therapeutics. Presidio’s current focus is on effective therapies for HCV infection. With a current pipeline consisting of compounds targeting both the NS5A and NS5B proteins of HCV, Presidio is well positioned to compete in the growing HCV therapy market. In addition to the NS5A inhibitor, PPI-668, Presidio is also developing a pan-genotypic non-nucleoside inhibitor, PPI-383, which is currently undergoing Phase 1 evaluation. Presidio’s goal is to discover and advance small-molecule, antiviral drug candidates that are potent, have pan-genotypic antiviral activity, offer convenient once-daily oral dosing and can be combined with other classes of HCV antivirals to combat viral resistance. The best future combination regimens will require such characteristics, to simplify patient treatment and to ensure that drug therapy will be effective against the wide variety of known HCV genotypes. For more information, please visit www.presidiopharma.com

Contacts

Presidio Pharmaceuticals, Inc.
Leo J. Redmond, 415-655-7560
Chief Financial Officer & Acting President
lredmond@presidiopharma.com

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