Interim results (SVR4) from a phase II all-oral combination study of Simeprevir and Samatasvir (IDX719) for the treatment of hepatitis C

Stockholm, Sweden—Medivir AB (OMX: MVIR), announces that Idenix Pharmaceuticals, Inc. today released interim data from the ongoing phase II HELIX-1 clinical trial evaluating an all-oral, direct-acting antiviral (DAA) HCV combination regimen of samatasvir (IDX719), Idenix’s once-daily pan-genotypic NS5A inhibitor, and simeprevir , a once-daily protease inhibitor jointly developed by Janssen R&D Ireland and Medivir AB, and ribavirin.

The combination regimen of the study was well-tolerated. In the treatment-naïve, non-cirrhotic, genotype 1b or 4 HCV-infected patients receiving 50 mg of samatasvir and 150 mg of simeprevir plus ribavirin for 12 weeks, 85 percent (n=17/20) of the patients achieved SVR4 (undetectable HCV RNA four weeks after end of treatment). The 50 mg dose of samatasvir is the selected dose in the ongoing 3-DAA HELIX-2 clinical trial. The HELIX-1 study results are expected to be presented at a scientific meeting in 2014.

HELIX-1 study design
The HELIX-1 trial is the first study in HCV-infected patients to commence under a non-exclusive collaboration agreement between Idenix and Janssen which was established in January 2013. The HELIX-1 trial is a phase II 12-week, randomized, parallel group study evaluating the antiviral activity, safety and tolerability of samatasvir and simeprevir in treatment-naïve, non-cirrhotic, genotype 1b or 4 HCV-infected patients.

Patients in part A of the study (n=63) were enrolled in one of three treatment groups receiving 50, 100, or 150 mg samatasvir once-daily for 12 weeks in combination with 150 mg of simeprevir plus a weight-based dose of ribavirin. In part B of the ongoing HELIX-1 study, exploratory cohorts of patients have been added to evaluate the safety and antiviral activity of a 25 mg dose of samatasvir in genotype 1b-infected patients and of a 100 mg dose of samatasvir in genotype 6-infected patients.

A second phase II trial (HELIX-2) was initiated in December 2013 evaluating samatasvir, simeprevir and TMC647055, a once-daily non-nucleoside polymerase inhibitor plus a low-dose ritonavir being developed by Janssen, with and without ribarivin in genotype 1-infected patients who are either treatment-naïve or have previously relapsed after treatment with pegylated interferon and ribavirin.

For additional information about the HELIX-1 study, please visit www.clinicaltrials.gov

For more information please contact:
Rein Piir, EVP Corporate Affairs & IR, mobile: +46 708 537 292

Medivir is required under the Securities Markets Act to make the information in this press release public. The information was submitted for publication at 13.15 p.m. CET on 13 January 2014.

About Simeprevir
Simeprevir is an NS3/4A protease inhibitor jointly developed by Medivir and Janssen R&D Ireland for the treatment of chronic hepatitis C infection in combination with other antivirals in HCV genotype 1 and 4 infected subjects with compensated liver disease, including cirrhosis.

Simeprevir was approved for the treatment of genotype 1 hepatitis C in September 2013 in Japan (trade name Sovriad™) and in the USA (trade name Olysio™) and Canada (trade name Galexos™) in November. A Marketing Authorisation Application was submitted to the European Medicines Agency (EMA) in April 2013 by Janssen-Cilag International NV seeking approval of simeprevir for the treatment of genotype 1 and genotype 4 chronic hepatitis C. To date, more than 3,700 patients have been treated with simeprevir in clinical trials.

About Samatasvir (IDX719)
Samatasvir is an NS5A inhibitor with low picomolar, pan-genotypic antiviral activity in vitro. To date, samatasvir has been safe and well-tolerated after single and multiple doses of up to 150 mg in healthy volunteers up to 14 days duration, and in HCV-infected patients up to 12 weeks duration. There have been no treatment-emergent serious adverse events reported in the program. Samatasvir has demonstrated potent pan-genotypic antiviral activity in HCV-infected patients with mean maximal viral load reductions up to approximately 4.0 log10 IU/mL across HCV genotypes 1-4 in a proof-of-concept, three-day monotherapy study.

About Medivir
Medivir is an emerging research-based pharmaceutical company focused on infectious diseases. Medivir has world class expertise in polymerase and protease drug targets and drug development which has resulted in a strong infectious disease R&D portfolio. The Company’s key pipeline asset is simeprevir, a novel protease inhibitor for the treatment of hepatitis C that is being developed in collaboration with Janssen R&D Ireland. The company is also working with research and development in other areas, such as bone disorders and neuropathic pain. Medivir has also a broad product portfolio with prescription pharmaceuticals in the Nordics.

For more information about Medivir AB, please visit the Company’s website: www.medivir.com

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Vertex Announces Sustained Viral Response Rate (SVR4) Data from All-Oral Study of VX-135 in Combination with Daclatasvir in Hepatitis C

January 9, 2014

BOSTON--(BUSINESS WIRE)-- Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced the first data from the initial cohorts of an open-label Phase 2a study of VX-135, Vertex's nucleotide analogue hepatitis C virus (HCV) polymerase inhibitor, in combination with daclatasvir, Bristol-Myers Squibb's NS5A replication complex inhibitor. In an intent-to-treat analysis, the sustained viral response rate four weeks after the completion of treatment (SVR4) was 83 percent (10 of 12) in treatment-naïve genotype 1 patients who received 200 mg of VX-135 in combination with daclatasvir. In this arm, one patient discontinued treatment after the first dose due to a serious adverse event of vomiting/nausea. The 11 other patients in this arm completed 12 weeks of treatment, and 91 percent (10 of 11) achieved SVR4. In the study, the majority of adverse events were mild.

"We are encouraged by these initial Phase 2a data for VX-135 in combination with another direct acting antiviral medicine," said Robert Kauffman, M.D., Ph.D., Senior Vice President and Chief Medical Officer at Vertex. "We believe that VX-135 has the potential to play an important future role in the treatment of hepatitis C, and we are currently evaluating these data with BMS to determine the next steps for this combination in people with hepatitis C, including people with genotypes 1 and 3."

About the Phase 2a Study

The data announced today are from the first two cohorts of an open-label Phase 2a study of VX-135 in combination with daclatasvir. The initial two cohorts of the study evaluated 100 mg and 200 mg once-daily doses of VX-135 in combination with daclatasvir once daily (60 mg) for 12 weeks of total treatment. Twenty-three people with chronic genotype 1 hepatitis C who were new to treatment (treatment-naïve) and did not have liver cirrhosis were enrolled in these cohorts. More than 75 percent of all patients enrolled had genotype 1a HCV. The majority of adverse events observed in the study were mild. The most common adverse events observed in greater than 10 percent of patients across the study were fatigue, headache and nausea. Safety and efficacy data for the two arms of the study are provided below:

• 200 mg of VX-135 in Combination with Daclatasvir (60 mg): In an intent-to-treat analysis, 58 percent (7 of 12) of patients had undetectable HCV RNA after 4 weeks of treatment and 83 percent (10 of 12) of patients had undetectable HCV RNA four weeks after the completion of treatment (SVR4). One patient in this arm experienced a serious adverse event of vomiting/nausea, discontinued treatment after the first dose and did not acheive SVR4. The 11 other patients in this arm completed 12 weeks of treatment, and 91 percent (10 of 11) achieved SVR4. One patient relapsed during the follow-up period and did not achieve SVR4.
• 100 mg of VX-135 in Combination with Daclatasvir (60 mg): In an intent-to-treat analysis, 73 percent (8 of 11) of patients achieved undetectable HCV RNA after 4 weeks of treatment and 73 percent (8 of 11) of patients had undetectable HCV RNA four weeks after the completion of treatment (SVR4). Two patients in this arm experienced viral breakthrough while receiving the combination regimen, and one patient relapsed during the follow-up period.

Vertex expects to submit these data for presentation at a medical meeting in 2014.

About VX-135

VX-135 is a uridine nucleotide analogue pro-drug designed to inhibit the replication of the hepatitis C virus by acting on the NS5B polymerase. Vertex gained worldwide rights to ALS-2200, known as VX-135 in Phase 2 studies, through an exclusive licensing agreement signed with Alios BioPharma, Inc. in June 2011.

About Vertex

Vertex is a global biotechnology company that aims to discover, develop and commercialize innovative medicines so people with serious diseases can lead better lives. Vertex scientists and our collaborators are working on new medicines to cure or significantly advance the treatment of cystic fibrosis, hepatitis C, rheumatoid arthritis and other life-threatening diseases. In addition to our clinical development programs, Vertex has more than a dozen ongoing preclinical programs aimed at other serious and life-threatening diseases.

Founded in 1989 in Cambridge, Mass., Vertex today has research and development sites and commercial offices in the United States, Europe, Canadaand Australia. For four years in a row, Science magazine has named Vertex one of its Top Employers in the life sciences. For additional information and the latest updates from the company, please visit www.vrtx.com.

Vertex Special Note Regarding Forward-Looking Statements

This press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, including, without limitation, Dr. Kauffman's statements in the second paragraph of the press release. While Vertex believes the forward-looking statements contained in this press release are accurate, there are a number of factors that could cause actual events or results to differ materially from those indicated by such forward-looking statements. Those risks and uncertainties include, among other things, that there is a partial clinical hold on VX-135 in the United States, that the outcomes of Vertex's clinical studies of VX-135 may not be favorable or support further development of VX-135 due to safety, efficacy, or other reasons, and the other risks listed under Risk Factors in Vertex's annual report and quarterly reports filed with the Securities and Exchange Commission and available through the company's website at www.vrtx.com. Vertex disclaims any obligation to update the information contained in this press release as new information becomes available.

(VRTX — GEN)

Vertex Pharmaceuticals Incorporated
Media:
Zach Barber, 617-341-6470
mediainfo@vrtx.com
or
Investors:
Michael Partridge, 617-341-6108
or
Kelly Lewis, 617-961-7530

Source: Vertex Pharmaceuticals Incorporated

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Frederick A. Nunes, MD, on trial results for difficult-to-treat patients with HCV

Provided by Healio

May 22, 2013

ORLANDO, Fla. — Frederick A. Nunes, MD, associate professor of medicine, at Penn Health Systems, discusses his presentation, “Interferon‐free Regimens of ABT‐450/r, ABT‐267, ABT‐333, and Ribavirin Achieve High Sustained Virologic Response 4 Weeks Post‐Treatment (SVR4) Rates in Patients With Chronic HCV Genotype 1 Regardless of Race, Ethnicity, or Other Baseline Characteristics” during Digestive Disease Week 2013.

Among HCV patients who are difficult to treat, including African-Americans, those with high BMI and insulin resistance, achieved a very high sustained response using three direct-acting antivirals and ribavirin, Nunes says.

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Pharmaceutical advances offer new options for health outcomes

Public release date: 20-May-2013

Contact: Aimee Frank
newsroom@gastro.org
407-685-4030
Digestive Disease Week

Research presented at DDW® 2013 feature new drugs for IBS, hepatitis C

Orlando, FL (May 20, 2013) — Research presented at Digestive Disease Week® (DDW) explores pharmaceutical advances for treating irritable bowel syndrome with diarrhea (IBS-D) and hepatitis C.

An international study holds promising results for patients suffering from IBS-D. In the phase II study, researchers found that the drug ibodutant significantly improved symptoms in more than 50 percent of the individuals treated.

"While there's been a lot of progress in medicines for IBS with constipation, we haven't seen the same in IBS with diarrhea," said Jan Tack, MD, professor and director of the division of gastroenterology and internal medicine at Leuven University in Belgium. "Up to this point, we haven't been able to provide a pharmaceutical option for this patient group that successfully manages the pain associated with the condition."

IBS is an extremely common condition, affecting an estimated 10 percent of adults. Funded by Menarini, the double-blind, multinational study recruited 559 patients with IBS-D who were randomized and treated with 1, 3 or 10 mg of ibodutant or a placebo. Patients took an oral tablet once daily for eight consecutive weeks. Researchers found that 10 mg was the most effective dose and that it worked best for females.

"These are exciting findings that could bring a lot of relief to many patients," said Dr. Tack said. "We're looking forward to moving into phase III to confirm our findings with a much larger sample of patients."

New therapy for patients with hepatitis C examined

New research suggests that an investigational therapy for patients with hepatitis C can achieve high response rates in a wide range of patients, even those who respond poorly to current treatments. The study examined the safety and efficacy of interferon-free regimens, including three direct-acting antiviral drugs with and without ribavirin, for 12 or 24 weeks, in patients with chronic hepatitis C who were either treatment-naïve or had previously failed standard treatment with peginterferon and ribavirin.

In the phase II study, researchers found that the treatment regimens achieved high sustained virologic response (SVR) rates, an efficacy measure of a hepatitis C treatment, in non-cirrhotic patients with HCV genotype-1 (GT 1). SVR was achieved by 98.7 percent of treatment-naïve patients and 93.3 percent of prior nonresponders after 12 weeks of treatment with three direct-acting agents with ribavirin.

"Hepatitis C genotype 1 is the most common type of hepatitis in the U.S., and many of these patients are still quite difficult to treat with current interferon-based therapies," said Frederick Nunes, MD, clinical associate professor of medicine at Penn Medicine. "This includes specific populations such as African Americans and patients with high body mass or pre-diabetes. These results suggest that highly effective regimens like this one may overcome that difficulty, without the need for interferon."

###

Assigning 247 patients to 12- or 24-week regimens, researchers found that four weeks after treatment, SVR rates were high regardless of patient characteristics previously associated with poorer response to interferon therapy. Funded by AbbVie (formerly Abbott), the study's results hold particular significance for patients who are older, black, Hispanic or have a higher body mass index.

Dr. Tack will present data from the study "Efficacy of ibodutant, a selective antagonist of neurokinin 2 receptors, in irritable bowel syndrome with diarrhoea (IBS-D): the results of a double-blind, randomised, placebo-controlled, parallel-group phase II study (The IRIS-2)," abstract 520, on Monday, May 20, at 8 a.m. ET in Room 300 of the Orange County Convention Center.

Dr. Nunes will present data from the study "Interferon-free Regimens of ABT-450/r, ABT-267, ABT-333, and Ribavirin Achieve High Sustained Virologic Response 4 Weeks Post-Treatment (SVR4 ) Rates in Patients With Chronic HCV Genotype 1 Regardless of Race, Ethnicity, or Other Baseline Characteristics" abstract 514, on Monday, May 20, at 8 a.m. ET in Room 203AB of the Orange County Convention Center.

Digestive Disease Week® (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Jointly sponsored by the American Association for the Study of Liver Diseases (AASLD), the American Gastroenterological Association (AGA) Institute, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Surgery of the Alimentary Tract (SSAT), DDW takes place May 18 to 21, 2013, at the Orange County Convention Center, Orlando, FL. The meeting showcases more than 5,000 abstracts and hundreds of lectures on the latest advances in GI research, medicine and technology. More information can be found at http://www.ddw.org.

Follow us on Twitter @DDWMeeting; hashtag #DDW13. Become a fan of DDW on Facebook.

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Achillion Announces Updated Phase 2 Results Including Early Sustained Virologic Response on ACH-3102 Plus Ribavirin in Genotype 1b Treatment-Naive Hepatitis C Patients

April 23, 2013

- ACH-3102 deemed safe and well-tolerated following 12 weeks of therapy -
- High barrier to resistance demonstrated with no on-treatment virologic breakthrough observed -
- Novel NS5A inhibitor study supports differentiated profile of ACH-3102 -

NEW HAVEN, Conn., April 23, 2013 (GLOBE NEWSWIRE) -- Achillion Pharmaceuticals, Inc. (Nasdaq:ACHN) today announced updated interim safety and efficacy results, including early sustained virologic response (SVR4) data, from the pilot Phase 2 trial evaluating once-daily ACH-3102 plus ribavirin (RBV) in treatment-naïve patients with genotype 1b, IL28B CC subtype, chronic hepatitis C virus (HCV) infection. All of the 8 patients enrolled in the trial completed 12 weeks of treatment with no virologic breakthrough observed. ACH-3102 also demonstrated continued declines in HCV RNA in the presence of up to six baseline mutations that are known to confer a high level of resistance to 1^st generations NS5A inhibitors. ACH-3102 was deemed safe and well-tolerated with no significant adverse events reported. In all, 75% of patients (6 of 8) had HCV RNA < 25 IU/ml at the end of treatment and 63% (5 of 8) achieved early sustained virologic response 4 weeks (SVR4) after the completion of therapy.

Dr. Andrew Muir, Principal Investigator and Assistant Professor of Medicine and Director of Gastroenterology/Hepatology Research at Duke Clinical Research Institute commented, "The preliminary results from this novel study of a single DAA, an NS5A inhibitor, plus ribavirin demonstrates the safety, high barrier to resistance, and preliminary efficacy of ACH-3102. The profound activity of ACH-3102 as a single DAA, along with its safety profile and lack of virologic breakthrough to date makes this a very promising compound to study further in combination with other oral agents, including sovaprevir, for the treatment of HCV."

Overall, ACH-3102 was well-tolerated and demonstrated a safety profile consistent with that seen during Phase 1 trials in both healthy subjects and HCV-infected patients. No patients experienced virologic breakthrough while on treatment and no patients discontinued treatment due to an adverse event. Final study results are expected to be submitted for presentation at a medical conference later this year.

	Virologic End Points
Total 8 subjects enrolled	RVR	ETR	SVR4
	n = 8	n = 8	n = 8
# of subjects	6 / 8	6 / 8*	5 / 8 **
(%)	(75%)	(75%)	(63%)
RVR = Rapid Virologic Response, HCV RNA < LLOQ ( < 25 IU/mL) at week 4 of treatment
ETR = End of Treatment Response, HCV RNA < LLOQ ( < 25 IU/mL) at week 12 of treatment
* The 2 patients who did not achieve ETR were started on pegylated interferon, ribavirin and telaprevir at the end of the 12-week treatment period, and demonstrated undetectable viral levels beginning at week 13.
** 1 patient with virologic relapse at week 15.

"We believe that these interim results further strengthen our position that ACH-3102 is a differentiated NS5A inhibitor possessing attributes that make it a true second-generation compound," commented Michael D. Kishbauch, President and Chief Executive Officer of Achillion. "The safety and efficacy profile support our recently initiated Phase 2 -007 trial evaluating 12 weeks of our protease inhibitor, sovaprevir, in combination with ACH-3012 for the treatment of genotype 1 HCV. With that study now underway, we look forward to reporting interim results beginning in the third quarter of this year, and will continue to explore and execute opportunities to combine our agents with other compounds that could further shorten the treatment duration or provide additional flexibility for treatment regimens to broadly cure HCV."

About ACH-3102

The NS5A protein is a clinically validated target that serves multiple functions at various stages of the HCV life cycle including involvement in virion production, interaction with host proteins and association with interferon-resistance. ACH-3102, Achillion's second generation NS5A inhibitor, has demonstrated potent activity against all HCV genotypes in vitro and in preclinical studies achieved additive to synergistic activity when combined with NS3 protease inhibitors, NS5B polymerase inhibitors, interferon and ribavirin. In preclinical studies, ACH-3102 demonstrated excellent potency, in the pico-molar range, against wild type HCV RNA replication, as well as potency against resistant mutants that have been identified in clinical studies. ACH-3102 was deemed to be safe and well-tolerated in Phase 1 development and achieved mean maximal reductions in HCV RNA of 3.78 log₁₀ after a single dose. ACH-3102 has been granted fast track designation by the FDA and is currently being evaluated in Phase 2 for the treatment of HCV.

About HCV

The hepatitis C virus is the most common cause of viral hepatitis, which is an inflammation of the liver. It is currently estimated that more than 170 million people are infected with HCV worldwide including more than 5 million people in the United States, making HCV more than twice as widespread as HIV. Three-fourths of the global HCV patient population is undiagnosed; it is a silent epidemic and a major global health threat. Chronic hepatitis, if left untreated, can lead to permanent liver damage that can result in the development of liver cancer, liver failure or death. Few therapeutic options currently exist for the treatment of HCV infection. The current standard of care is limited by its specificity for certain types of HCV, significant side-effect profile, and injectable route of administration.

About Achillion Pharmaceuticals

Achillion is an innovative pharmaceutical company dedicated to bringing important new treatments to patients with infectious disease. Achillion's proven discovery and development teams have advanced multiple product candidates with novel mechanisms of action. Achillion is focused on solutions for the most challenging problems in infectious disease including HCV and resistant bacterial infections. For more information on Achillion Pharmaceuticals, please visit www.achillion.com or call 1-203-624-7000 begin_of_the_skype_highlighting 1-203-624-7000 end_of_the_skype_highlighting.

Forward-Looking Statements

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 important factors that could cause actual results to differ materially from those indicated by such forward-looking statements, including statements with respect to: the expected potency, safety, tolerability, effectiveness and other characteristics of sovaprevir and ACH-3102; and Achillion's expectations regarding timing for the commencement, completion and reporting of results of its clinical trials of both ACH-3102 in combination with ribavirin and sovaprevir in combination with ACH-3102. We may use words such as "expect," "anticipate," "project," "intend," "plan," "believe," "seek," " estimate," and "may" and similar expressions to identify such forward-looking statements. Among the important factors that could cause actual results to differ materially from those indicated by such forward-looking statements are risks relating to, among other things Achillion's ability to: replicate in later clinical trials positive results found in earlier stage clinical trials of sovaprevir, ACH-3102 and its other product candidates; advance the development of its drug candidates under the timelines it anticipates in current and future clinical trials; obtain necessary regulatory approvals; obtain patent protection for its drug candidates and the freedom to operate under third party intellectual property; establish commercial manufacturing arrangements; identify, enter into and maintain collaboration agreements with appropriate third-parties; compete successfully with other companies that are seeking to develop improved therapies for the treatment of HCV; manage expenses; and raise the substantial additional capital needed to achieve its business objectives. These and other risks are described in the reports filed by Achillion with the U.S. Securities and Exchange Commission, including its Annual Report on Form 10-K for the fiscal year ended December 31, 2012 and its subsequent SEC filings.

In addition, any forward-looking statement in this press release represents Achillion's views only as of the date of this press release and should not be relied upon as representing its views as of any subsequent date. Achillion disclaims any duty to update any forward-looking statement, except as required by applicable law.

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Gilead Announces Update on Phase 3 Study of Oral Fixed-Dose Combination of Sofosbuvir and Ledipasvir for Genotype 1 Hepatitis C Patients

-- Enrollment in ION-1 Study Continues Following Planned DSMB Review --

FOSTER CITY, Calif.--(BUSINESS WIRE)--Mar. 26, 2013-- Gilead Sciences, Inc. (Nasdaq: GILD) today provided an update on ION-1, a Phase 3 clinical trial evaluating a once-daily fixed-dose combination of the nucleotide sofosbuvir and the NS5A inhibitor ledipasvir with and without ribavirin (RBV) for 12 or 24 weeks among treatment-naïve genotype 1 patients with hepatitis C virus (HCV) infection (n=800). A planned review by the study's Data and Safety Monitoring Board (DSMB) of safety data from 200 patients in all four arms and of SVR4 rates (sustained virologic response four weeks after completion of therapy) from 100 patients in the two 12-week duration arms concluded that the trial should continue without modification. This recommendation is based upon the observed SVR4 rates exceeding the predefined threshold of 60 percent and the absence of significant safety issues. Enrollment of the remaining 600 patients in ION-1 is now underway.

Sofosbuvir/ledipasvir is also being evaluated in a second Phase 3 study, ION-2, initiated in January 2013, which is now fully enrolled. ION-2 is evaluating sofosbuvir/ledipasvir with RBV for 12 weeks, and with and without RBV for 24 weeks, among 400 treatment-experienced genotype 1 HCV patients. Participants in this study failed to respond to past therapy containing pegylated interferon (peg-IFN) or peg-IFN plus a protease inhibitor.

Sofosbuvir, ledipasvir and the sofosbuvir/ledipasvir fixed-dose combination are investigational products and their safety and efficacy have not yet been established.

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 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 the ION-1 study, the possibility that the proportion of patients who maintain a sustained virologic response with longer follow up will not be as favorable as the SVR4 rates observed in the study, and the possibility of unfavorable results from ION-2 and other ongoing and subsequent clinical trials involving sofosbuvir and the fixed-dose combination of sofosbuvir/ledipasvir. In addition, Gilead may make a strategic decision to discontinue development of sofosbuvir, ledipasvir and/or the fixed-dose combination regimen if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. As a result, these compounds may never be successfully commercialized. 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 Annual Report on Form 10-K for the year ended December 31, 2012, 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.

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)
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EASL 2012: New HCV Drug Induces Rapid, Durable Drops in Viral Load

From Medscape Medical News

Daniel M. Keller, PhD

April 30, 2012 (Barcelona, Spain) — In 3 phase 2 trials of GS-7977, there was a concordance between the sustained virologic response (SVR) 4 weeks after the end of therapy (SVR4) and SVRs at 12 and 24 weeks after therapy (SVR12 and SVR24) in treatment-naive patients infected with hepatitis C virus (HCV) genotypes 1, 2, or 3.

No patient relapsed after posttreatment week 12, and 99% of patients with SVR4 for whom posttreatment week 12 data were available achieved SVR12, Eric Lawitz, MD, from Alamo Medical Research in San Antonio, Texas, reported here at the International Liver Congress 2012.

GS-7977 (formerly PSI-7977) is a specific nucleotide analogue inhibitor of HCV NS5B RNA polymerase and is taken orally once daily. Previous reports have shown that it has broad antiviral activity against HCV genotypes 1, 2, and 3, with or without interferon, in treatment-naive patients, and has a high barrier to the development of viral resistance.

The aim of the study was to evaluate concordance between SVR4 and SVR12 or SVR24 among treatment-naive patients taking GS-7977 400 mg daily in the PROTON (n = 144), ELECTRON (n = 120), and ATOMIC (n = 332) phase 2 clinical trials. The trial protocols differed somewhat, but in general were various combinations and durations of GS-7977, pegylated interferon (Peg-IFN), and ribavirin.

In the PROTON and ATOMIC trials, depending on viral genotype, patients received GS-7977 plus Peg-IFN/ribavirin for 12 weeks followed by Peg-IFN for 12 weeks, Peg-IFN/ribavirin alone for 48 weeks, GS-7977 plus Peg-IFN/ribavirin for 12 or 24 weeks, GS-7977 plus PegIFN/ribavirin for 12 weeks followed by 12 weeks of GS-7977 alone or by GS-7977 plus ribavirin.

In the ELECTRON trial, some patients with genotypes 2 or 3 virus received similar combinations but only out to 12 weeks. Other patients with genotypes 1, 2, or 3 received GS-7977 plus ribavirin for 12 weeks.

The analysis involved only patients treated with GS-7977 400 mg in combination with interferon, ribavirin, or both for at least 4 weeks who had SVR4 plus SVR12 or SVR4 plus SVR24 data available. Of the 596 patients in the 3 studies, 259 (43%) were eligible for analysis.

At baseline in all treatment groups, mean age ranged from 43 to 52 years, and most patients were white, male, had similar body mass indices (mean, 26 to 28 kg/m²), and had interleukin-28B genotype non-CC. Mean baseline HCV RNA levels were mainly in the range of 6.3 to 6.7 log₁₀ IU/mL.

Dr. Lawitz presented results for virologic response at the end of therapy and for SVR4, SVR12, and SVR24.

"If we look at all regimens and look at the concordance between SVR4 and SVR12, we can see that 249 of the 251 [patients] were concordant between SVR4 and SVR12 — a concordance rate of 99%," he said. "If we look at concordance between SVR4 and SVR24, we can see that although the numbers are smaller, there is complete concordance — all 107 patients who had an SVR4 achieved an SVR24.... The concordance held, irrespective of the presence or absence of interferon. However, the dataset is fairly small in the noninterferon arm, limiting conclusions."

Dr. Lawitz concluded that "much of the concordance is due to the high response rates observed across all treatment groups. To date, relapse after week 4 is infrequent and was only observed in patients who received a peg-interferon-containing regimen."

Session moderator George Papatheodoridis, MD, associate professor of medicine and gastroenterology at the Medical School of Athens University, staff member at Hippokration General Hospital, in Athens, Greece, and a member of the European Association for the Study of the Liver Governing Board Scientific Committee, told Medscape Medical News that GS-7977 "is a very interesting, very promising molecule. It seems to be rather safe and very effective, even in combination with ribavirin." Dr. Papatheodoridis was not involved in any of the studies.

In terms of new drugs to treat HCV, he said, "some of the new molecules are very genotype-specific.... Most of the protease inhibitors are developed to work only for genotype 1; some of them work for genotype 2, but not 3 and 4. The nucleoside polymerase inhibitors seem to work better across almost all genotypes, so this is the only class [of drug] that is not that genotype-specific."

Dr. Papatheodoridis wondered about the use of SVR4 as a standard efficacy measure. "I don't think that SVR4 will and should be the standard for SVR," he told Medscape Medical News. "Of course, we know that the FDA and most of the physicians have now accepted SVR12. So probably...SVR12 is going to be the standard for reporting trials in the near future. Still, with all these combinations, patients should have at least 1 examination, maybe 6 months or 12 months after SVR12, so we can be sure that this SVR remains over time. I think that SVR12 is going to be the standard from now on, but the patients treated with the new regimens should be followed for a bit longer."

He admitted that SVR4 looks predictive of later sustained responses. "You expect most of the patients to relapse soon after stopping treatment [if they are going relapse]. Of course, SVR4 is reasonable; we know and we expect that it is going to be associated with SVR12 and SVR24. There is no rush to decide the SVR just 4 weeks after treatment.... We should be sure that we eradicated the virus," he cautioned.

Dr. Lawitz reports financial relationships with Abbott, Achillion Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, GlobeImmune, Idenix Pharmaceuticals, Idera Pharmaceuticals, Inhibitex Pharmaceuticals, Medarex, Medtronic, Merck, Novartis, Pharmasset, Roche, sanofi-aventis, Schering-Plough, Santaris Pharmaceuticals, Scynexis Pharmaceuticals, Tibotec, Vertex Pharmaceuticals, ViroChem Pharma, and ZymoGenetics. Dr. Papatheodoridis has disclosed no relevant financial relationships.

The International Liver Congress 2012: Abstract 7. Presented April 19, 2012.

Source

EASL 2012: [SLIDES] Interim Sustained Virologic Response Rates in Treatment-Naïve HCV Genotype 1a and 1b Patients Treated for 12 or 24 Weeks with an Interferon-Free All-Oral Quad Regimen

Gilead Sciences, Inc.
333 Lakeside Drive
Foster City, CA 94404
Tel: (650)522-6009
Fax: (650)522-5260

Poster
Number 1421

47th Annual Meeting of the
European Association for the Study of the Liver
April 18 - 22, 2012
Barcelona, Spain

M. Sulkowski1, M. Rodriguez-Torres2, E. Lawitz3, M. Shiffman4, S. Pol5, R. Herring6, J.G. McHutchison7, P.S. Pang7, K.A. Wong7, B. Massetto7, Y. Zhu7, D.M. Brainard7, D. Wyles8, F. Habersetzer9

1Johns Hopkins University School of Medicine, Lutherville, MD; 2Fundacion de Investigacion de Diego, Santurce, PR; 3Alamo Medical Research, San Antonio, TX; 4Liver Institute of Virginia, Richmond, VA; 5Hôpital Necker, Paris, France; 6Nashville Gastrointestinal Specialists, Inc.,
Nashville, TN; 7Gilead Sciences, Inc., Foster City, CA; 8University of California, San Diego, La Jolla, CA; 9Hôpitaux Universitaires de Strasbourg, Strasbourg, France

Introduction

• Combinations of direct-acting antivirals (DAAs) without interferon (IFN) have demonstrated variable rates of sustained virologic response (SVR) in genotype 1 patients1,2
  ─ Lower SVR rates have been reported in genotype 1a as compared to genotype 1b HCV
  ─ The optimal duration of IFN-free treatment regimens in genotype 1 has not been established
  ─ Virologic failure in IFN-free regimens without a nucleos(t)ide analogue has been associated with multidrug resistance
• This ongoing Phase 2 study (NCT01353248) was designed to assess the effi cacy and safety of a 3-DAA-containing regimen plus ribavirin (RBV), including a protease inhibitor, NS5A inhibitor, and a non-nucleoside NS5B inhibitor
• We report preliminary SVR4, SVR12, and safety data from patients treated for 12 or 24 weeks

Table 1. In Vitro Characteristics of DAAs Administered in the Current Study

*In vitro and following 3 or 7 days of monotherapy in HCV-infected patients

Methods

Patients

Major inclusion criteria:

• Chronic infection with HCV genotype 1a or 1b
• HCV treatment-naïve
• Plasma HCV RNA ≥104 IU/mL during screening
• Exclusion of cirrhosis by liver biopsy within 2 years or Fibroscan within 6 months

Major exclusion criteria:

• Coinfection with human immunodefi ciency virus or hepatitis B virus
• Contraindication to treatment with IFN and/or RBV
• Current or prior hepatic decompensation
• Prespecifi ed laboratory abnormalities

Study design (Figure 1)

• Patients were randomized 1:2 to the following treatment groups:
  ─ Arm 1: GS-5885 30 mg QD + GS-9451 200 mg QD + GS-9190 30 mg BID + RBV
  ─ Arm 2: GS-5885 90 mg QD + GS-9451 200 mg QD + GS-9190 30 mg BID + RBV
• Patients with HCV RNA ≥25 IU/mL at Week 2 (non-vRVR) were offered peginterferon (PEG)-containing rescue therapy or discontinuation from the study
• Patients in Arm 2 with HCV RNA <25 IU/mL from Week 2 through Week 10 were
  re-randomized at Week 12 to either stop treatment or continue treatment through Week 24

Figure 1. Study Design 

• Randomization stratifi ed by HCV RNA at screening (≤ or >800,000 IU/mL) and genotype 1a or 1b
• Virologic breakthrough defi ned as confi rmed, on-treatment HCV RNA ≥25 IU/mL after Week 2
  ─ Patients with breakthrough offered PEG-containing rescue therapy
• Plasma HCV RNA measured using the Roche COBAS TaqMan HCV/HPS assay v2.0 with a lower limit of quantifi cation of 25 IU/mL

Table 2. Summary of Baseline Characteristics (N = 140)

Figure 2. Patient Disposition

Table 3. Preliminary Post-treatment Response Rates by Treatment Arm and
Genotype Subtype, n (%)

*SVR4 and SVR12 rates calculated using treatment completers who had available data at the given timepoint

Figure 3. On-treatment Response by Arm, IL28B Genotype, and HCV Subtype

Figure 4. HCV RNA Kinetics in Patients with Virologic Breakthrough by Treatment Arm and Genotype Subtype

45 patients enrolled in rescue Rescue therapy with PEG + GS-5885 + GS-9451

Table 4. Patients Achieving HCV RNA <25 IU/mL During Rescue Therapy

a. 1 early termination (ET) due to lack of effi cacy; 1 ET due to an AE
b. ET due to lack of effi cacy; 1 of 16 patients experienced breakthrough after achieving <25 IU/mL
c. 1 ET due to lack of effi cacy; 1 ET due to an AE; 1 patient has not reached <25 IU/mL after 16 weeks in rescue

Table 5. Safety Summary, n (%)

• One subject in Arm 1 had 2 SAEs (pancreatitis requiring overnight hospitalization and viral gastroenterititis); no doses of study medications were missed
• Two subjects in Arm 2 had 5 AEs (acute psychosis, alcohol intoxication, decreased muscle mass, heartburn, irritability)
• Reported grade 3 AEs were pancreatitis (also SAE), stomatitis, fatigue, elevated bilirubin, viral gastroenteritis (also SAE), alcohol poisoning (led to study discontinuation), tendonitis, and acute psychosis

Table 6. Most Common (≥10%) Treatment-Emergent AEs, n (%) Arm 1 (GS-5885 30 mg) Arm 2

Table 7. Laboratory Parameters of Interest, n (%)

• Rates and severity of anemia were consistent with what has been reported in other IFN-free, RBV-containing studies3,4
• Indirect hyperbilirubinemia was observed in approximately 60% of patients without concomitant transaminase elevations
  ─ GS-9451 is an inhibitor of the bilirubin transporter protein OATP1B1 and has been associated with transient indirect hyperbilirubinemia in healthy volunteers5
  ─ No Grade 4 (≥6.0 g/dL) hyperbilirubinemia was observed

Summary and Conclusions

Preliminary data from this ongoing Phase 2 study of a multi-DAA
regimen without a nucleos(t)ide analogue has shown in genotype 1
patients that:

• A regimen including 3 DAAs + RBV was well tolerated for up to 24 weeks
• The 90-mg dose of GS-5885 provides improved antiviral effi cacy over the 30-mg dose of GS-5885 without an increase in toxicity
• Rates of viral breakthrough and relapse were lower in genotype 1b patients than in genotype 1a patients
• Patients with the IL28B CC genotype showed lower rates of breakthrough than IL28B non-CC patients, particularly in Arm 2 (GS-5885 90mg)
• Virologic breakthrough was associated with multi-DAA resistance
  ─ Viral suppression with the addition of PEG occurs in most virologic failures

References and Acknowledgements

1. Lok A, et al. N Engl J Med 2012;366;3:216-24.
2. Zeuzem S, et al. Gastroenterology 2011;141:2047-54.
3. Zeuzem et al. AASLD 2011. Abstract LB-15
4. Gane EJ, et al. AASLD 2011. Abstract 34
5. Yang JC, et al. EASL 2012.

The study team and investigators thank the patients for their participation in this clinical trial.

© 2012 Gilead Sciences, Inc.

Source

EASL 2012: Investigational Compound Peginterferon Lambda Achieved SVR24 Rates Comparable to Peginterferon Alfa with Fewer Flu-Like and Musculoskeletal Symptoms in Phase IIb Study in Treatment-Naïve Genotype 2 or 3 Hepatitis C Patients

April 19, 2012 12:00 PM Eastern Daylight Time

• First report of sustained virologic response (SVR) results for Lambda interferon
• Numerically greater virologic response rates consistent at 4 weeks (RVR*), throughout treatment, and maintained through SVR₂₄^† in Lambda 180 µg dose versus alfa

• Data presented at The International Liver Congress in Barcelona

PRINCETON, N.J.--(BUSINESS WIRE)--Bristol-Myers Squibb Company (NYSE: BMY) today announced results from the Phase IIb EMERGE clinical trial in 118 treatment-naïve patients chronically infected with genotype 2 or 3 hepatitis C virus (HCV). In this study, the investigational compound peginterferon lambda-1a (Lambda) plus ribavirin (RBV) achieved sustained virologic response rates 24 weeks post-treatment (SVR₂₄) that were comparable to peginterferon alfa-2a (alfa) plus ribavirin. Rates of SVR₂₄ ranged from 60.0% to 75.9% in the Lambda/RBV arms versus 53.3% in the alfa/RBV arm (n=30). The 180 µg dose arm of Lambda/RBV achieved SVR₂₄ in 75.9% (n=29) and was the dose selected for phase III clinical trials.

In this study, adverse events were mostly low grade and self-limited. Overall, rates of serious adverse events and adverse events were similar across treatment arms up to SVR₂₄. There were fewer flu-like and musculoskeletal symptoms in the Lambda/RBV arms. Additionally, lower rates of anemia, neutropenia, and thrombocytopenia were observed and there were fewer interferon and ribavirin dose reductions for anemia in the Lambda/RBV arms. Two (2) cases of hyperbilirubinemia >5x the upper limit of normal (ULN) were observed in the Lambda 240 µg dose arm and zero (0) cases of hyperbilirubinemia >5x the upper limit of normal (ULN) were observed in the Lambda 180 µg, Lambda 120 µg, and alfa arms.

These EMERGE study findings in hepatitis C genotype 2 and 3 patients were presented in an oral session at the International Liver Congress (ILC), the 47^th annual meeting of the European Association for the Study of the Liver (EASL) in Barcelona, Spain.

“There is a significant unmet medical need for antiviral therapies that can benefit more hepatitis C patients with a goal of decreasing treatment-related adverse events and potentially reducing treatment duration," said Stefan Zeuzem, MD, chief of the department of medicine and professor of medicine at the Goethe University Hospital in Frankfurt, Germany. "The EMERGE study results of peginterferon lambda versus peginterferon alfa in patients infected with HCV genotype 2 or 3 demonstrate that peginterferon lambda, in combination with ribavirin, may have the potential to help address these unmet needs, and these data support further studies of this investigational Lambda interferon.”

Study Results

Viral Response

The primary endpoint of the study was the proportion of patients with complete early virologic response (cEVR^‡). Treatment with all doses of Lambda achieved cEVR rates similar to alfa (Lambda 240 µg: 86.7%, Lambda 180 µg: 96.6%, Lambda 120 µg: 89.7%, and alfa: 86.7%). Higher rates of RVR were achieved in the Lambda arms [Lambda 240 µg: 66.7% (p<0.05), Lambda 180 µg: 75.9% (p<0.05), Lambda 120 µg: 44.8% vs. alfa: 30%]. In patients with HCV genotypes 2 and 3, treatment with all doses of Lambda achieved SVR₂₄ rates similar to PEG-Interferon alfa [Lambda 240 µg: 60.0% (n=30), Lambda 180 µg: 75.9% (n=29), Lambda 120 µg: 65.5% (n=29), and alfa: 53.3%, (n=30)].

Safety

Overall, the rates of serious adverse events and adverse events were similar across treatment arms up to SVR₂₄. In this study, there were some differences seen in the relative frequency of adverse events between lambda and alfa. Some of the adverse events commonly associated with interferon treatment such as flu-like symptoms (Lambda 240 µg: 23.3%; Lambda 180 µg: 20.7%; Lambda 120 µg: 17.2%; alfa: 40.0%), musculoskeletal symptoms (Lambda 240 µg: 16.7%; Lambda 180 µg: 20.7%; Lambda 120 µg: 27.6%; alfa: 63.3%), constitutional symptoms such as fatigue (Lambda 240 µg: 50.0%; Lambda 180 µg: 27.6%; Lambda 120 µg: 41.4%; alfa: 53.3%), neutropenia < 750/mm³ (Lambda 180 µg: 0.0%, n=29; alfa: 27.5%, n=30), anemia with hemoglobin < 10 g/dL or a decline of > 3.4g/dL (Lambda 180 µg: 6.9%, n=29; alfa: 44.8%, n=30), and thrombocytopenia < 100,000/mm³ (Lambda 180 µg: 0.0%, n=29; alfa: 24.1%, n=30) were less frequently seen with Lambda than with alfa. Some others such as psychiatric (Lambda 240 µg: 40.0%; Lambda 180 µg: 41.4%; Lambda 120 µg: 44.8%; alfa: 33.3%) and neurologic (Lambda 240 µg: 36.7%; Lambda 180 µg: 24.1%; Lambda 120 µg: 27.6%; alfa: 33.3%) adverse events were similar across groups.

The proportion of patients that required interferon dose reductions were: Lambda 240 µg: 13.3%; Lambda 180 µg: 6.9%; Lambda 120 µg: 6.9%; alfa: 26.7%, and the proportion of patients that required withheld and/or reduced ribavirin were: Lambda 240 µg: 23.3%; Lambda 180 µg: 6.9%; Lambda 120 µg: 24.1%; alfa: 43.3%. The proportion of patients who required ribavirin dose reductions for low hemoglobin were: Lambda 240 µg: 0.0%; Lambda 180 µg: 0.0%; Lambda 120 µg: 0.0%; alfa: 23.3%.

The proportion of patients with elevated liver enzymes [AST or ALT > 10x the upper limit of normal (ULN)] were: Lambda 240 µg: 3.3%; Lambda 180 µg: 0.0%; Lambda 120 µg: 0.0%; alfa: 0.0%. Total bilirubin was also elevated > 5.0x ULN in the highest-dose Lambda treatment arm compared with PEG-Interferon alfa (Lambda 240 µg: 6.7%; Lambda 180 µg: 0.0%; Lambda 120 µg: 0.0%; alfa: 0.0%); all resolved following interferon dose modification and/or discontinuation.

About the EMERGE Phase IIb Study

The EMERGE study is a two-part, randomized, controlled, multicenter, phase II study of peginterferon lambda-1a in treatment-naïve patients with chronic hepatitis C genotype 1, 2, 3 or 4. Part one of EMERGE was a Phase IIa study, and results were previously presented at The American Association for the Study of Liver Diseases (AASLD) 2010 Liver Meeting.

Part two of EMERGE is an ongoing, blinded Phase IIb study designed to evaluate the safety, efficacy, and pharmacokinetics of Lambda versus alfa, both in combination with ribavirin. In the study, the 526 non-cirrhotic patients were randomized into four dose groups: Lambda 240 µg, Lambda 180 µg, Lambda 120 µg, and alfa 180 µg. Of the 526 patients, 118 patients with genotype 2 or 3 chronic hepatitis C were randomized into four dose groups: Lambda 240 µg (n=30), Lambda 180 µg (n=29), Lambda 120 µg (n=29) and alfa 180 µg (n=30). The results for these 118 patients were presented today at The International Liver Congress 2012.

Phase IIb RVR and cEVR results for genotypes 1, 2, 3, and 4 were previously presented at The International Liver Congress in 2011. The study continued for 24 weeks in genotype 2 and 3 patients and will continue for 48 weeks in genotype 1 and 4 patients. The primary endpoint of the study is the proportion of patients who achieve complete early virologic response (cEVR). HCV RNA and safety were assessed through 48 weeks (24-weeks on-treatment and 24-weeks post-treatment or to SVR₂₄).

About Bristol-Myers Squibb’s Commitment to Liver Disease

Bristol-Myers Squibb is researching a portfolio of compounds that aim to address unmet medical needs across the liver disease continuum, including hepatitis C, hepatitis B and liver cancer. The Company’s hepatitis C pipeline includes a portfolio of compounds with different mechanisms of action, pursuing both biologics as well as small molecule antivirals. These compounds are being studied as part of multiple novel treatment regimens with the goal of increasing SVR rates across diverse patient types and geographies. Peginterferon lambda-1a is the first investigational type III interferon in Phase IIb development for the treatment of hepatitis C. Native human interferon lambda proteins are generated by the immune system in response to viral infection, and signal through a different receptor than native human interferon alfa proteins. Lambda receptors are present on fewer cell types within the human body than alfa receptors. This restricted distribution of the interferon lambda receptor offers the potential for more targeted delivery of interferon therapy.

About Hepatitis C

Hepatitis C is a virus that infects the liver and is transmitted through direct contact with infected blood and blood products. An estimated 170 million people worldwide are infected with hepatitis C. Up to 90 percent of those infected with hepatitis C will not clear the virus and will become chronically infected. Twenty percent of people with chronic hepatitis C will develop cirrhosis and, of those, up to 25 percent may progress to liver cancer. Although there is no vaccine to prevent hepatitis C, it is a potentially curable disease.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information, please visit http://www.bms.com or follow us on Twitter at http://twitter.com/bmsnews.

Bristol-Myers Squibb Forward Looking Statement

This press release contains "forward-looking statements" as that term is defined in the Private Securities Litigation Reform Act of 1995 regarding the research, development and commercialization of pharmaceutical products. Such forward-looking statements are based on current expectations and involve inherent risks and uncertainties, including factors that could delay, divert or change any of them, and could cause actual outcomes and results to differ materially from current expectations. No forward-looking statement can be guaranteed. Among other risks, there can be no guarantee that the compounds described in this release will move from exploratory development into full product development, that the clinical trials of these compounds will support regulatory filings, or that the compounds will receive regulatory approvals or, if approved, that they will become commercially successful products. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Bristol-Myers Squibb's business, particularly those identified in the cautionary factors discussion in Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended December 31, 2011, in our Quarterly Reports on Form 10-Q and our Current Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events or otherwise.

^* Rapid virologic response (RVR): undetectable viral load (HCV RNA <25 IU/mL) at week 4

† Sustained Virologic Response 24 or SVR₂₄: undetectable viral load 24 weeks post-treatment, demonstrative of cure

^‡ Complete Early Virologic Response or cEVR: undetectable viral load at week 12

Contacts

Bristol-Myers Squibb
Media:
Cristi Barnett, 609-252-6028
cristi.barnett@bms.com
or
Investors:
John Elicker, 609-252-4611
john.elicker@bms.com

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Gilead, Bristol Put Profits Ahead of Best Care for Hep C Patients

By Adam Feuerstein 04/19/12 - 10:24 AM EDT

BARCELONA (TheStreet) -- The most effective new therapy for hepatitis C -- two pills that could cure nearly every patient treated -- may never see the light of day because the developers of these new medicines, Bristol-Myers Squibb(BMY_) and Gilead Sciences(GILD_), seem unable to work together.

Apparently, profits are more important than best patient care.

The new Hep C therapy at issue here combines Bristol's daclatasvir with Gilead's GS-7977. Each is a single pill administered once a day. The results from this new therapy are nothing short of spectacular -- an early cure rate of 100% for genotype 1 patients and 91% of genotype 2/3 patients, according to data from a mid-stage study announced Thursday at the European Association for the Study of Liver Disease (EASL) meeting.

A 100% cure rate for genotype 1 patients! Obviously, results can't get better than that.

You'd think there'd be a rush to move the combination regimen of daclatasvir and GS-7977 into a larger, confirmatory phase III trial, but you'd be mistaken. Amazingly, this most promising new treatment for hepatitis C patients may actually be discontinued because Bristol and Gilead can't work together. 

Ckick here to continue reading ....

EASL 2012: Gilead Announces Early Sustained Virologic Response Rates for GS-7977 Plus Ribavirin in Genotype 1 Treatment-Na ïve Hepatitis C Patients

- Interim Results Reported from ELECTRON and QUANTUM Studies -

BARCELONA, Spain, Apr 19, 2012 (BUSINESS WIRE) --Gilead Sciences, Inc. (Nasdaq: GILD) today announced interim data from the Phase 2 ELECTRON study examining the investigational once-daily oral agent GS-7977 plus ribavirin (RBV) in treatment-naïve patients with genotype 1 chronic hepatitis C virus (HCV) infection. Of the 25 patients who completed 12 weeks of treatment with the GS-7977-based regimen, 88 percent of patients (n=22/25) remained HCV RNA undetectable four weeks after completion of treatment. Three patients experienced viral relapse. These findings are being presented this week during a poster session (Poster #1113) at the 47^th Annual Meeting of the European Association for the Study of the Liver (International Liver Congress 2012) in Barcelona, Spain.

"These preliminary results suggest that 12 weeks of therapy with once-daily oral GS-7977 and ribavirin may be enough to cure hepatitis C in many genotype 1 patients, including those who are currently not candidates to receive interferon," said Professor Edward Gane, MD, Deputy Director and Hepatologist, New Zealand Liver Transplant Unit, Auckland City Hospital in New Zealand, and principal investigator of the ELECTRON study. "Further investigation of GS-7977 in a variety of patient populations and combinations will be important in assessing the drug's potential as part of an all-oral regimen for hepatitis C."

Results from three additional arms of the ELECTRON study examining GS-7977-based therapy in various patient populations are also being presented this week at the International Liver Congress. These include null responder genotype 1 patients, and genotype 2 and genotype 3 patients, both treatment-naïve and prior non-responders.

Overall, GS-7977 was well tolerated and exhibited a favorable safety profile. No patients experienced viral rebound during treatment. No patients discontinued therapy due to an adverse event. The most common adverse events were fatigue, dizziness and headache, and two grade 3/4 laboratory abnormalities were reported.

Gilead today also announced interim results from a second Phase 2 trial (QUANTUM) examining a 12- and 24-week duration of GS-7977 plus RBV in treatment-naïve patients. Twenty-five patients were randomized to the 12-week treatment arm: 19 genotype 1 patients; four genotype 3 patients; and two genotype 2 patients. Two genotype 1 patients discontinued therapy prematurely during the 12-week treatment period. At the four-week post-treatment time period, data were available for 17 genotype 1 patients. Of these, 10/17 (59 percent) remained HCV RNA undetectable. Seven patients (41 percent) experienced viral relapse. Additionally, seven of the patients who have reached the eight week post-treatment time period, and who achieved SVR4, remain HCV RNA undetectable.

The overall safety and efficacy profile of GS-7977 was consistent with that seen in ELECTRON. No patients experienced viral rebound while on treatment and no patients discontinued therapy due to an adverse event.

Eleven of the 25 patients (44 percent) in ELECTRON and three of 19 patients (16 percent) in QUANTUM had the IL28B C/C genetic polymorphism. Each of the three patients who relapsed in the ELECTRON study had a different IL28B polymorphism (C/C, C/T or T/T). The seven patients who relapsed in the QUANTUM study either had IL28B C/T (n=4) or IL28B T/T (n=3) genetic polymorphisms. Patients in both studies will continue to be observed to determine sustained virologic response rates at weeks 12 and 24 of follow-up (SVR12 and SVR24).

"The early results from these studies confirm that GS-7977 has the potential to become the cornerstone of an efficacious, all-oral combination regimen for many patients with chronic hepatitis C infection," said John McHutchison, MD, Senior Vice President, Liver Disease Therapeutics, Gilead Sciences. "We look forward to more data unfolding as our trials progress and we expect to initiate additional studies with GS-7977 in combination with other oral antivirals in our pipeline in the coming months. Our goal is to develop a short, simple, safe and effective single tablet regimen for HCV patients throughout the world."

About ELECTRON

ELECTRON is an ongoing Phase 2 randomized open-label clinical study evaluating GS-7977 for the treatment of chronic HCV infection. The primary endpoint of the trial is the safety and tolerability of GS-7977 400 mg once-daily for 8 or 12 weeks, with and without RBV and/or Peg-IFN in HCV patients with genotypes 1, 2 or 3. Study populations include treatment-naïve non-cirrhotic patients and those who have failed prior interferon based therapies or "null" responders.

About QUANTUM

QUANTUM is a Phase 2 randomized double-blind placebo-controlled clinical study evaluating GS-7977 for the treatment of chronic HCV infection. The current active arms of the trial are examining GS-7977 400 mg once-daily plus RBV for 12 or 24 weeks in cirrhotic and non-cirrhotic treatment-naïve HCV patients with genotypes 1, 2 and 3. The results announced today are for the cohort of patients who have received and completed 12 weeks of therapy with GS-7977 plus RBV (n=25).

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 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 that the proportion of patients who maintain a sustained virologic response 12 and 24 weeks post-treatment will not be as favorable as the sustained virologic response rates reported in this press release and the possibility of unfavorable results from additional arms of the ELECTRON and QUANTUM studies and subsequent clinical trials involving GS-7977 and RBV. As a result, GS-7977, including in combination with other oral antivirals in Gilead's pipeline, may never be successfully commercialized. Further, Gilead may make a strategic decision to discontinue development of the compounds if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. In addition, Gilead may be unable to develop an all-oral antiviral regimen for HCV genotype 1 patients or a pangenotypic regimen for all HCV patients. 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 Annual Report on Form 10-K for the year ended December 31, 2011, 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.

For more information on Gilead Sciences, please visit the company's website at www.gilead.com or call Gilead Public Affairs at 1-800-GILEAD-5 or 1-650-574-3000.

SOURCE: Gilead Sciences, Inc.

Gilead Sciences, Inc.
Susan Hubbard, 650-868-5215 (Investors)
shubbard@gilead.com
Patrick O'Brien, 650-522-1936 (Investors)
pobrien@gilead.com
Cara Miller, 650-576-7849 (Media)
cmiller@gilead.com

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EASL 2012: Phase 2b Data Show SVR12 in Cirrhotic HCV Patients Treated with Interferon-Free Regimen

April 19, 2012

Boehringer Ingelheim announces first data of BI 201335 + BI 207127 and ribavirin in genotype-1 HCV patients with compensated cirrhosis

Barcelona, Spain and Ridgefield, CT, April 19, 2012 – New data from a descriptive sub-analysis of patients with compensated liver cirrhosis show that up to 43 percent of genotype-1a (GT1a) and up to 71 percent of GT1b hepatitis C virus (HCV) patients achieved sustained viral response (SVR12). SVR12 has been highly correlated with SVR24, which is a recognized indicator of viral cure. This descriptive sub-analysis from SOUND-C2, a Phase 2b study evaluating interferon-free treatment with Boehringer Ingelheim's investigational direct-acting antiviral (DAA) compounds BI 201335 and BI 207127 plus ribavirin (RBV), includes HCV GT1a and 1b patients with compensated liver cirrhosis, regardless of IL-28B allele status.

Presented today (poster #1420) at the International Liver Congress™, the 47th Annual Meeting of the European Association of the Study of the Liver (EASL 2012), in Barcelona, Spain, this analysis from the SOUND-C2 study is the first dataset for an interferon-free regimen in HCV patients with compensated liver cirrhosis. SVR12 results from the SOUND-C2 study were highlighted today during an official EASL press conference and will be presented in full as part of an oral abstract session on Saturday, April 21 (oral abstract #101).

"HCV patients with cirrhosis are in urgent need of treatment to preserve liver function," said Stefan Zeuzem, M.D., Chief of the Department of Medicine and Professor of Medicine at the Johann Wolfgang Goethe University Hospital in Frankfurt, Germany and one of the study investigators. "The results from this analysis of SOUND-C2 show the potential to achieve viral cure at rates similar to those seen with current therapies but without interferon in advanced genotype-1 HCV patients and warrant further evaluation."

Liver cirrhosis, where liver cells are either damaged or killed and replaced by scar tissue, causes liver function to deteriorate over time and increases the risk of liver cancer and liver transplant. In the United States, HCV is one of the most common causes of cirrhosis, with up to 20 percent of chronic HCV patients developing the condition.

"Today, one in five patients with HCV develops cirrhosis. It's important to investigate treatment options to determine if they are both effective and well tolerated in this patient population," said Peter Piliero, M.D., Vice President, Clinical Development and Medical Affairs, Boehringer Ingelheim Pharmaceuticals, Inc. "Through our HCVerso™ clinical trial program, we are working with HCV experts from around the world to continue to design programs that investigate treatment with BI 201335 and BI 207127 in real-world settings, with the aim of extending a cure to more patients."

SVR12 Descriptive Sub-Analysis of Cirrhotic Patients in SOUND-C2

The SOUND-C2 open-label Phase 2b study includes 362 treatment-naïve GT1 HCV patients, randomized into five interferon-free treatment groups, each with 120 mg BI 201335 once-daily (QD), but with different dosing of BI 207127 and treatment durations.

This descriptive sub-analysis includes 37 patients with biopsy or Fibroscan confirmed cirrhosis. All 37 patients had compensated liver disease: 24 were GT1b and 30 had IL-28B genotype CT/TT. Patients who received the three times daily (TID) dose of BI 207127 (Arms A, B and C) were pooled.

SVR12 in Compensated Cirrhosis

	BI 201335 QD/ BI 207127 TID/RBV (Pooled A, B and C)		BI 201335 QD/ BI 207127 BID/RBV (Arm D)		BI 201335 QD/ BI 207127 TID (No RBV) (Arm E)
	GT1a n=7	GT1b n=14	GT1a n=6	GT1b n=7	GT1a n=0	GT1b n=3
SVR12* N (%)	3 (43)	9 (64)	2 (33)	5 (71)	0 (0)	1(33)

*SVR12 is defined as undetectable HCV RNA 12 weeks after treatment discontunation, except for Arm C (BI 201335 + BI 207127 + RBV for 40 weeks). In Arm C, SVR4 (undetectable HCV RNA 4 weeks after treatment discontinuation) is included in this analysis as SVR12 data are not available.

None of the patients in this descriptive sub-analysis treated with BI 207127 twice-daily (BID) experienced relapse after treatment completion. One of the 13 patients (8 percent) in the BI 207127 TID pooled group (Arms A, B and C) of the analysis experienced relapse. Breakthrough occurred in five patients (38 percent) in the BID Arm, four patients (19 percent) in the pooled group (Arms A, B and C) and two patients (67 percent) in the BI 207127 TID Arm with no RBV (Arm E).

Seven patients (19 percent) in the descriptive sub-analysis discontinued treatment early due to adverse events (AEs), with rash, photosensitivity, and jaundice caused by isolated hyperbilirubinemia (not associated with liver dysfunction) being the most commonly reported. Four patients (19 percent) in the
BI 207127 TID pooled group (Arms A, B and C) experienced serious AEs compared with two patients (15 percent) in the BI 207127 BID Arm (Arm D). No discontinuations due to rash, jaundice, or photosensitivity occurred in the BID Arm of the analysis.

The investigators noted that further evaluation of interferon-free treatment with BI 201335 and BI 207127 in patients with cirrhosis is warranted.

Other BI data being presented at the EASL Annual Meeting include:

Selected for Oral Presentation and Inclusion in Official EASL Press Office Activities

Title	Lead Author	Presentation Details
SOUND-C2 interim results: SVR4 and SVR12 with an interferon-free regimen of BI 201335 and BI 207127 +/- ribavirin, in treatment-naïve patients with chronic genotype-1 HCV infection	S. Zeuze m	Oral Abstract #101 Date: Sat, April 21 Time: 8:30 - 8:45 a.m. CEST/ 2:30 - 2:45 a.m. EDT EASL press conference Date: Thur, April 19 Time: 11:00 a.m. - 12:00 p.m. CEST/ 5:00 - 6:00 a.m. EDT

Poster Presentations

Title	Lead Author	Presentation Details
Characterization of HCV NS3 variants that emerged during virologic breakthrough and relapse from BI 201335 Phase 2 SILEN-C2 study in pegylated-interferon plus ribavirin treatment-experienced patients	G. Kukolj	Poster#1185 Date: Sat, April 21 Time: 12:30 - 1:30 p.m. CEST/ 6:30 - 7:30 a.m. EDT
Impact of early response definitions on duration and outcome of treatment with BI 201335 plus pegylated-interferon plus ribavirin	M. Sulkowski	Poster# 1209 Date: Sat, April 21 Time: 12:30 - 1:30 p.m. CEST/ 6:30 - 7:30 a.m. EDT
Preclinical characterization of the hepatitis C virus NS5B polymerase non-nucleoside inhibitor BI 207127	P. Beaulieu	Poster# 822 Date: Fri, April 20 Time: 12:30 - 2:00 p.m. CEST/ 6:30 - 8:00 a.m. EDT

 

About Hepatitis C Virus (HCV)

HCV is an infectious disease of the liver and is a leading cause of chronic liver disease, transplant and failure that affects as many as 170 million people globally, with three to four million new infections occurring each year. In the United States, an estimated 4.1 million Americans have been infected with HCV, of which approximately 3.2 million have chronic HCV infection. The majority – about 75 to 85 percent – of HCV cases will develop into chronic infection. It is estimated 20 percent of patients with chronic HCV will develop cirrhosis within 20 years of infection. The mortality rate after cirrhosis has developed is 2 – 5 percent per year. Chronic HCV infection is the cause of an estimated 8,000 to 10,000 deaths annually in the United States.

About Boehringer Ingelheim in Hepatitis C Virus (HCV)

Boehringer Ingelheim has a long-standing commitment to virology, including developing innovative therapies for HCV and HIV/AIDS. Through pioneering science, BI strives to achieve a far reaching and inclusive HCV cure that may ease the impact of the disease. In partnership with the scientific community, our clinical trial program, HCVerso™, is rigorously designed to find answers to the challenges that HCV patients face, including those who are the most difficult to treat.

BI 201335, an investigational oral HCV NS3/4A protease inhibitor that has shown the potential to improve cure rates as compared to PegIFN/RBV therapy alone, has completed clinical trials through Phase 2b (SILEN-C studies). A multi-study Phase 3 trial program currently is underway to evaluate BI 201335 combined with PegIFN/RBV in treatment-naïve, treatment-experienced and HIV co-infected patients with chronic genotype-1 HCV.

BI 207127, an NS5B RNA-dependent polymerase inhibitor that has shown the potential to eliminate interferon from HCV treatment when combined with BI 201335 and RBV, is currently being investigated in Phase 2 trials in interferon-sparing regimens.

About Boehringer Ingelheim Pharmaceuticals, Inc.

Boehringer Ingelheim Pharmaceuticals, Inc., based in Ridgefield, CT, is the largest U.S. subsidiary of Boehringer Ingelheim Corporation (Ridgefield, CT) and a member of the Boehringer Ingelheim group of companies.

The Boehringer Ingelheim group is one of the world’s 20 leading pharmaceutical companies. Headquartered in Ingelheim, Germany, it operates globally with 145 affiliates and more than 42,000 employees. Since it was founded in 1885, the family-owned company has been committed to researching, developing, manufacturing and marketing novel products of high therapeutic value for human and veterinary medicine.

As a central element of its culture, Boehringer Ingelheim pledges to act socially responsible. Involvement in social projects, caring for employees and their families, and providing equal opportunities for all employees form the foundation of the global operations. Mutual cooperation and respect as well as environmental protection and sustainability are intrinsic factors in all of Boehringer Ingelheim’s endeavors.

For more information, please visit http://us.boehringer-ingelheim.com and follow us on Twitter at http://twitter.com/boehringerus.

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