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.

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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.

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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.

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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.

Source

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.”

Source

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

Source

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

Source

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

Source

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

Source

Conatus Pharmaceuticals Presents Late-Breaking Poster at AASLD Annual Meeting

Key Biomarker Data From Phase 1 Trial of Emricasan in Patients With Hepatic Impairment

SAN DIEGO, Nov. 10, 2014 (GLOBE NEWSWIRE) -- Conatus Pharmaceuticals Inc. (Nasdaq:CNAT) today is presenting its late-breaking poster at The Liver Meeting®, the annual meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston November 7-11, 2014. The poster (#LB16), entitled "Rapid and statistically significant reduction of markers of apoptosis and cell death in subjects with mild, moderate and severe hepatic impairment treated with a single dose of the pan-caspase inhibitor, emricasan," will be available for viewing in the Poster Hall on the second floor of the John B. Hynes Convention Center today, Monday, November 10, 2014, from 8:00 a.m. to 5:30 p.m. ET and authors will be available for discussion at the poster from 12:30 p.m. to 2:00 p.m. ET. The poster is available on the Events & Presentation page in the Investor Center of the Conatus website at www.conatuspharma.com.

The poster highlights key secondary endpoint pharmacodynamic (PD) biomarker results from the company's recently completed Phase 1 hepatic impairment clinical trial. The trial was conducted in 12 subjects with mild, 8 subjects with moderate, and 8 subjects with severe hepatic impairment, as defined using Child-Pugh Scores, and 8 healthy matched control subjects. All subjects received a single 50 mg oral dose of emricasan, and serial blood samples were collected over a 48-hour period. Levels of three key biomarkers of apoptosis, overall cell death, and caspase enzymatic activity – caspase-cleaved cytokeratin 18 (cCK18), full-length cytokeratin 18 (flCK18), and caspase 3/7, respectively – were elevated at study baseline and demonstrated rapid and statistically significant reductions after a single 50 mg oral dose of emricasan. Importantly, levels of these three key biomarkers demonstrated significant reductions from the elevated levels at baseline in 100% of the hepatic impaired subjects compared with 0% of the matched control subjects, whose baseline levels were not elevated. In all three impaired groups, peak reductions of caspase 3/7 occurred approximately 4 hours after dosing, and peak reductions in cCK18 and flCK18 levels occurred 8 to 12 hours after dosing. All three biomarkers trended toward pre-dose levels within 24 to 48 hours after dosing. Noteworthy conclusions from the study included:

• Mechanism-specific biomarkers of apoptosis and caspase enzymatic activity, together with a biomarker of overall cell death, are elevated in subjects with advanced liver disease.
• Biomarker elevations were rapidly reduced after a single dose of emricasan in all hepatic impaired patients.
• Since elevation of these biomarkers is related to disease pathology and progression, emricasan may provide clinical benefit to patients with advanced stages of liver disease.

"We had previously demonstrated emricasan's ability to rapidly reduce disease-elevated biomarkers of caspase activity, apoptosis and overall cell death in patients with earlier-stage liver disease," said Conatus co-founder, Senior Vice President of Research and Chief Scientific Officer, Alfred P. Spada, Ph.D., "and we are pleased that the current study showed significant and rapid reductions in these biomarkers after a single dose of emricasan in patients in more advanced stages of liver disease. We believe these biomarkers measure key drivers in the progression of liver disease, and we look forward to completing our ongoing trials to determine whether biomarker reductions correlate with clinical benefits for patients."

Conatus initiated three clinical trials of emricasan in patients with impaired organ function to support dose selection and prioritization for advancement in its overall clinical development program: a Phase 2b trial initiated in September 2013 in acute-on-chronic liver failure (ACLF) patients who may have simultaneous impairment of both liver and kidney function; a Phase 1 trial initiated in January 2014 in patients with severe renal impairment; and the previously described Phase 1 hepatic impairment trial initiated in April 2014. Preliminary pharmacokinetic (PK) results from the renal impairment and hepatic impairment trials were used to support the design of two recently initiated trials in patients with liver cirrhosis. Aggregate final data from these three trials are expected to be sufficient to inform on optimal dosing of emricasan, and future direction for the clinical development of emricasan, in potential future studies over a broad range of patient populations, including critically ill patients with varying degrees of liver and kidney function.

About Emricasan Clinical Development

Conatus is developing emricasan for the treatment of patients with chronic liver disease and acute exacerbations of chronic liver disease, including ACLF, liver cirrhosis (LC), portal hypertension (PH), post-orthotopic liver transplant (POLT) recipients with reestablished liver fibrosis post-transplant as a result of recurrent hepatitis C virus (HCV) infection who have successfully achieved a sustained viral response (SVR) following HCV antiviral therapy (POLT-HCV-SVR), and nonalcoholic fatty liver disease (NAFLD), including patients with inflammatory and/or fibrotic nonalcoholic steatohepatitis (NASH). Conatus is also supporting a pilot clinical study funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) in patients with severe alcoholic hepatitis. To date, emricasan has been studied in over 550 subjects in twelve clinical trials.

About Conatus Pharmaceuticals

Conatus is a biotechnology company focused on the development and commercialization of novel medicines to treat liver disease. Conatus is developing its lead compound, emricasan, for the treatment of patients with chronic liver disease and acute exacerbations of chronic liver disease. Emricasan is a first-in-class, orally active pan-caspase protease inhibitor designed to reduce the activity of enzymes that mediate inflammation and cell death, or apoptosis. Conatus believes that by reducing the activity of these enzymes, emricasan has the potential to interrupt the disease progression across the spectrum of liver disease. For additional information, please visit www.conatuspharma.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward-looking statements, including statements regarding the elevation of biomarkers related to liver disease pathology and progression, emricasan's potential to impact on the biomarkers and the progression of liver disease, the potential for the PK data to inform on optimal dosing of emricasan in future studies in potential target patient populations, the role of caspase activity and apoptosis in disease pathology and progression, and emricasan's potential to provide clinical benefit to patients across a broad spectrum of liver disease, including patients with advanced stages of liver disease. In some cases, you can identify forward-looking statements by terms such as "may," "will," "should," "expect," "plan," "anticipate," "could," "intend," "target," "project," "contemplates," "believes," "estimates," "predicts," "potential" or "continue" or the negative of these terms or other similar expressions. These forward-looking statements speak only as of the date of this press release and are subject to a number of risks, uncertainties and assumptions, including:  dosing of emricasan beyond a single dose, the applicability of the biomarkers as potential drivers of liver disease progression, the effect on liver disease of decreasing the biomarkers, the determination of the most appropriate patients for enrollment in the company's Phase 2 clinical trial in patients with cirrhosis, the potential for competing products to limit the clinical trial enrollment in the company's Phase 2 clinical trials, the company's ability to successfully enroll patients in and complete its Phase 2 clinical trials; the company's reliance on third parties to conduct its clinical trials, including the enrollment of patients, and manufacture its clinical drug supplies of emricasan; potential adverse side effects or other safety risks associated with emricasan that could delay or preclude its approval; results of future clinical trials of emricasan; the company's ability to obtain additional financing in order to complete the development and commercialization of emricasan; and those risks described in the company's prior press releases and in the periodic reports it files with the Securities and Exchange Commission. The events and circumstances reflected in the company's forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Except as required by applicable law, the company does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise.

Alan Engbring
(858) 376-2637

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Arrowhead Presents Data on ARC-520 and ARC-AAT at AASLD The Liver Meeting® 2014

- ARC-520 shows statistically significant reduction in HBsAg through day 43 after a single injection (p < 0.05)

- Repeat dosing of ARC-AAT in primates shows reduction of approximately 90% of serum alpha 1 antitrypsin (AAT) with long duration of effect suggesting that monthly or less frequent dosing may be sufficient for sustained suppression of hepatic AAT production

- ARC-AAT abstract highlighted in the AASLD President’s Press Conference as a promising new treatment

- Arrowhead will host an investor event and presentation to discuss results that will be webcast at 8:00 p.m. EST

November 10, 2014 09:15 AM Eastern Standard Time

AASLD 2014

PASADENA, Calif.--(BUSINESS WIRE)--Arrowhead Research Corporation (NASDAQ: ARWR), a biopharmaceutical company developing targeted RNAi therapeutics, today announced that initial data from the ongoing Phase 2a study of ARC-520, its RNAi therapeutic candidate for the treatment of chronic hepatitis B (HBV) infection, was presented today in the late-breaking poster session at the 2014 American Association for the Study of Liver Diseases (AASLD) Liver Meeting in Boston. Arrowhead also delivered a plenary presentation with new preclinical efficacy data on ARC-AAT, its RNAi therapeutic candidate for the treatment of liver disease associated with Alpha-1 antitrypsin deficiency.

“We presented some important advancements today for both ARC-520 and ARC-AAT”

The Company will host an investor event and presentation to discuss these results that will be webcast tonight at 8:00 p.m. EST. Investors may access the webcast and presentation slides on the Events page of the Company’s website at http://ir.arrowheadresearch.com/events.cfm. An audio only version of the live webcast may also be accessed by calling 844-825-4406 toll-free from the U.S., or 315-625-3230 for international callers, using conference ID 31449966. An archive of the call will be available for seven days and may be accessed by calling 855-859-2056 or 404-537-3406. Copies of the AASLD poster and plenary presentation will also be available to view on the Events page of the Company’s website.

“We presented some important advancements today for both ARC-520 and ARC-AAT,” said Christopher Anzalone, Ph.D., Arrowhead’s President and Chief Executive Officer. “These programs and our expanding pipeline of RNAi therapeutics continue to generate exciting data that further validate the utility of the DPC delivery system. We have seen clear activity across multiple preclinical models and are now seeing activity in humans. We are still dose escalating in the ARC-520 Phase 2a, where dosing is complete in the 3 mg/kg cohort and screening has begun for 4 mg/kg. We believe that the initial data from the first two dose cohorts as well as safety data from the Phase 1 volunteer study are encouraging and support advancement of the program into multi-dose Phase 2b studies. We are currently preparing regulatory filings for the ARC-520 Phase 2b and the ARC-AAT Phase 1, both of which we expect to be filed this quarter. We intend to initiate those studies soon after receiving regulatory permission to begin.”

ARC-520 Data

In a Late-Breaking Poster titled, “Phase II, dose ranging study of ARC-520, a siRNA-based therapeutic, in patients with chronic hepatitis B virus infection,” interim data on ARC-520 was presented by Man-Fung Yuen, M.D., Ph.D., Chair of Gastroenterology and Hepatology, and Li Shu Fan Medical Foundation Professor in Medicine, The University of Hong Kong, and a principal investigator for the study. The poster included up-to-date safety data on ARC-520 from this study, an ongoing Phase 2a multicenter, randomized, double-blind, placebo-controlled, dose-escalation study, as well as a recently completed Phase 1 normal volunteer study.

The nine dose group, Phase 1, normal volunteer trial was designed to characterize the safety profile of ARC-520 across a range of doses and evaluate pharmacokinetics. It was a single-center, randomized, double-blind, placebo-controlled, single dose-escalation, first-in-human study of ARC-520 administered intravenously to healthy adult volunteers for which partial data has been previously reported. All subjects received either placebo or ARC-520 in doses ranging from 0.01 mg/kg to 4.0 mg/kg. The study successfully enrolled all 54 subjects (36 received ARC-520, 18 placebo). The Phase 2a study has enrolled three dose cohorts including 24 patients, 18 receiving drug and 6 receiving placebo. Unblinded data is available for the first two cohorts. Cohort 3 data collection is ongoing and this cohort remains blinded. Full results for the first two dose cohorts at 1.0 mg/kg and 2.0 mg/kg and partial (blinded) safety results from the 3.0 mg/kg dose cohort were included in the poster.

In both studies, there have been no reports of serious AEs, no dose limiting toxicities, no discontinuations due to AEs, and a modest overall occurrence rate of AEs without a clear dose-related increase in frequency or severity. There has been a modest occurrence rate of non-clinically significant abnormal laboratory tests. There were no reported drug related or clinically significant differences for vital signs or ECGs between subjects receiving drug versus placebo. To date, ARC-520 when administered as a single dose up to 4.0 mg/kg to healthy volunteers and up to 3.0 mg/kg to patients with chronic HBV appears to be well tolerated.

Arrowhead also reported initial results for depth and duration of hepatitis B surface antigen (HBsAg) reduction in the Phase 2a study. In cohort 1 (1.0 mg/kg), the mean nadir of HBsAg was -39% (range -22 to -57) with a mean change on day 85 of -31% (range -14 to -39). In cohort 2 (2.0 mg/kg), the mean nadir of HBsAg was -51% (range -46 to -59) with a mean change on day 85 of -22% (range -7 to -40). For cohort 2, the percent reduction in HBsAg was statistically significant versus placebo (p < 0.05) for days 3 through 43 post-dose. For cohort 2, the mean day of HBsAg nadir was day 33 with a range of day 8 to day 57.

Arrowhead believes that this is the first time that a reduction in HBsAg mediated through RNA interference has been demonstrated in patients with chronic HBV infection. This study is ongoing with follow up continuing on Cohort 3 (3.0 mg/kg) and recruitment underway for a fourth cohort of patients at 4.0 mg/kg.

Preparations are underway to initiate a series of multi-dose Phase 2b studies of ARC-520, for which the Company plans to file with regulatory authorities in the fourth quarter of 2014. These studies are planned to have clinical sites in the US, Western Europe, Asia, and potentially other countries and/or regions. Several studies are currently contemplated, including ARC-520 in combination with entecavir or tenofovir as well as combination studies that add an immunostimulatory agent.

ARC-AAT Data

Arrowhead also presented data on ARC-AAT, its clinical candidate for the treatment of liver disease associated with Alpha-1 Antitrypsin Deficiency (AATD), a rare genetic disease that severely damages the liver and lungs of affected individuals. These patients synthesize a mutant form of AAT (Z-AAT) in the liver which is poorly secreted and accumulates, resulting in liver injury. The goal of treatment with ARC-AAT is to silence production of Z-AAT thereby preventing further accumulation of Z-AAT in the liver and potentially reversing pre-existing liver injury and fibrosis.

The presentation in the prestigious Plenary Session titled, “A hepatocyte-targeted RNAi-based treatment for liver disease associated with alpha-1 antitrypsin deficiency,” was presented by Christine Wooddell, Ph.D., Group Leader, Arrowhead Research. AASLD President Dr. Adrian Di Bisceglie, MD, FACP also highlighted the presentation, along with just ten others, in the President’s Press Conference as a program that holds great promise for patients.

In preclinical studies with PiZ mice, which are genetically modified to produce the mutant human AAT (Z-AAT), ARC-AAT induced a greater than 95 percent reduction in circulating AAT after a single dose with a long duration of effect. Area covered by Z-AAT globules and globule size within the liver were significantly reduced after a single dose of ARC-AAT at day 15 post-dose (p < 0.005) and day 29 post-dose (p < 0.01). Multi-dose studies in PiZ mice showed that ARC-AAT was effective at reducing and preventing Z-AAT aggregates in the liver. At week 13 of the study, after 4 biweekly doses, the ARC-AAT treated group show 99% less soluble (monomer) Z-AAT and 79% less insoluble (polymer) Z-AAT, normalized to a saline control group. Thus, injection of ARC-AAT in transgenic mice expressing human Z-AAT resulted in prevention and reduction of Z-AAT globules and, importantly, liver inflammation.

In primate studies, a 90% reduction of AAT in serum was observed after a single injection, which persisted for over ten weeks with greater than 80 percent knockdown observed at the six-week time point. Multi-dose studies in primates showed a sustained reduction of AAT with once every six weeks dosing, suggesting that once monthly or less frequent dosing may be sufficient to maintain approximately 80-90% knockdown in humans. The treated animals showed no changes in clinical chemistry (ALT, AST, BUN, Creatinine), indicating that ARC-AAT appeared to be well tolerated at these optimal therapeutic dose levels.

About ARC-520

Arrowhead’s RNAi-based candidate ARC-520 is designed to treat chronic HBV infection by reducing the expression and release of new viral particles and key viral proteins. The goal is to achieve a functional cure, which is an immune clearant state characterized by hepatitis B s-antigen negative serum with or without sero-conversion. The siRNAs in ARC-520 intervene at the mRNA level, upstream of where nucleotide and nucleoside analogues act. In transient and transgenic mouse models of HBV infection, a single co-injection of Arrowhead’s Dynamic Polyconjugate (DPC) delivery vehicle with cholesterol-conjugated siRNA targeting HBV sequences resulted in multi-log knockdown of HBV RNA, proteins and viral DNA with long duration of effect. Arrowhead has completed enrollment in a Phase 1 single ascending dose study in normal volunteers. The company is conducting a single dose Phase 2a study in chronic HBV patients, and expects to follow with multi-dose, multi-national Phase 2b studies. Approximately 350 million people worldwide are chronically infected with the hepatitis B virus. Chronic HBV infection can lead to cirrhosis of the liver and is responsible for 80% of primary liver cancers globally.

About ARC-AAT

Arrowhead has developed ARC-AAT for the treatment of liver disease associated with Alpha-1 Antitrypsin Deficiency (AATD), a rare genetic disease that severely damages the liver and lungs of affected individuals. ARC-AAT employs a novel unlocked nucleobase analog (UNA) containing RNAi trigger molecule designed for systemic delivery using the Dynamic Polyconjugate delivery system. ARC-AAT is highly effective at knocking down the Alpha-1 antitrypsin (AAT) gene transcript and reducing the hepatic production of the mutant AAT (Z-AAT) protein. Reduction of liver production of the inflammatory Z-AAT protein, which has been clearly defined as the cause of progressive liver disease in AATD patients, is important as it is expected to halt the progression of liver disease and potentially allow fibrotic tissue repair. The Company plans to file with regulatory authorities in the fourth quarter of 2014 and commence clinical studies shortly after receiving permission to begin.

About Arrowhead Research Corporation

Arrowhead Research Corporation is a biopharmaceutical company developing targeted RNAi therapeutics. The company is leveraging its proprietary Dynamic Polyconjugate delivery platform to develop targeted drugs based on the RNA interference mechanism that efficiently silences disease-causing genes. Arrowhead’s pipeline includes ARC-520 for chronic hepatitis B virus, ARC-AAT for liver disease associated with Alpha-1 antitrypsin deficiency, and partner-based programs in obesity and oncology.

For more information please visit http://www.arrowheadresearch.com, or follow us on Twitter @ArrowRes. To be added to the Company's email list and receive news directly, please visit http://ir.arrowheadresearch.com/alerts.cfm.

Source: Arrowhead Research Corporation

Contacts

Arrowhead Research Corporation
Vince Anzalone, CFA
626-304-3400
ir@arrowres.com
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Investor Relations:
The Trout Group
Lauren Glaser
646-378-2972
ir@arrowres.com
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Media:
Russo Partners
Martina Schwarzkopf, Ph.D.
212-845-4292
martina.schwarzkopf@russopartnersllc.com

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