Gilead Announces Phase 2 Results for Sofosbuvir-Based Regimens in Hepatitis C Patients Before and After Liver Transplantation

~ Studies Support Efficacy and Safety of an All-Oral Sofosbuvir-Based Regimen for the Prevention and Treatment of Recurrent HCV Infection Following Liver Transplants ~

WASHINGTON--(BUSINESS WIRE)--Nov. 2, 2013-- Gilead Sciences, Inc. (Nasdaq: GILD) today announced results from two Phase 2 studies evaluating an all-oral treatment regimen of the investigational once-daily nucleotide analogue sofosbuvir plus ribavirin (RBV) for both the prevention and treatment of recurrent chronic hepatitis C virus (HCV) infection among patients who undergo liver transplantation. The findings will be presented this week at the 64^th Annual Meeting of the American Association for the Study of Liver Diseases (The Liver Meeting 2013) in Washington, D.C.

HCV infection is the most common cause of liver transplantation in the United States and Europe. Recurrence of HCV infection is universal among patients with active disease at the time of transplantation and up to 50 percent develop cirrhosis of the liver within five years. Suppression of HCV RNA prior to liver transplantation should reduce the risk of re-infection and its serious complications, but currently available treatment options are often ineffective and poorly tolerated. Similarly, in the post-transplant setting, treatment is generally poorly tolerated and complicated by strong drug interactions with immunosuppressive agents used to prevent the body’s rejection of the transplanted liver.

In a study conducted among pre-transplant HCV patients (Study 2025), up to 48 weeks of sofosbuvir/RBV therapy was administered. Among patients with undetectable HCV (<25 IU/mL) at the time of transplantation, 64 percent (n=25/39) achieved undetectable HCV RNA 12 weeks post-transplant (pTVR12). Patients who achieve pTVR12 are considered cured of HCV infection. In a second study conducted among post-transplant HCV patients (Study 0126), patients with established recurrent HCV infection following liver transplantation received 24 weeks of sofosbuvir/RBV therapy. Seventy-seven percent (n=27/35) of patients in this study have achieved a sustained virologic response four weeks post-treatment (SVR4).

“Recurrence of HCV following liver transplantation almost always occurs in clinical practice. These patients are at higher risk for disease progression, the development of cirrhosis, liver graft failure, re-transplantation and increased morbidity and mortality,” said Michael P. Curry, MD, Medical Director, Liver Transplantation at Beth Israel Deaconess Medical Center, Boston, and an investigator for the pre- and post-liver transplant trials. “In these studies, sofosbuvir clearly demonstrated the potential to improve patient outcomes by either preventing or effectively treating recurrent HCV infection following liver transplantation.”

Three percent and five percent of patients discontinued treatment due to adverse events in the pre- and post-transplant studies, respectively. No serious adverse events reported were associated with sofosbuvir. The most common adverse events observed were consistent with the safety profile of RBV, and included fatigue, anemia, headache and nausea in the pre-transplant study, and fatigue, headache, arthralgia (joint pain) and diarrhea in the post-transplant study.

About the Pre-Transplant Study

Study 2025 is an on-going open-label Phase 2 study evaluating the efficacy and safety of sofosbuvir (SOF) 400 mg once daily plus weight-based ribavirin (RBV) for up to 48 weeks or until liver transplantation. Sixty-one patients with HCV infection (Child-Pugh class A or B cirrhosis) and liver cancer, who were either treatment-naïve or treatment-experienced were enrolled.

About the Post-Transplant Study

Study 0126 is an ongoing open-label Phase 2 study evaluating the efficacy and safety of 24 weeks of treatment with sofosbuvir 400 mg once-daily plus RBV (starting at 400 mg/day) among 40 treatment-naïve and treatment-experienced patients with recurrent HCV infection. Patients in the study had received a transplant a median of four years prior to the study, and 40 percent were cirrhotic.

There were no deaths, graft losses or episodes of organ rejection among post-liver transplantation patients in the study.

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

Sofosbuvir is an investigational product and its safety and efficacy have not 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 and South America, Europe and Asia Pacific.

Forward-Looking Statement

This press release includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are subject to risks, uncertainties and other factors, including the possibility of unfavorable longer-term results from Studies 025 and 126 and other ongoing and subsequent clinical trials involving sofosbuvir, alone or in combination with other products, for the treatment of HCV. In addition, regulatory authorities will not approve sofosbuvir for HCV-related indications and any marketing approval may have substantial limitations on its use. As a result, sofosbuvir may never be successfully commercialized. Further, Gilead may make a strategic decision to discontinue development of sofosbuvir if, for example, Gilead believes commercialization will be difficult relative to other opportunities in its pipeline. These risks, uncertainties and other factors could cause actual results to differ materially from those referred to in the forward-looking statements. The reader is cautioned not to rely on these forward-looking statements. These and other risks are described in detail in Gilead’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2013, 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)

Cara Miller, 650-522-1616 (Media)

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Sofosbuvir: ATU French cohort is in place, but limited

This article has been translated from French to English

Posted by Renaud Persiaux on October 30, 2013, 1:18:03 p.m

The temporary use authorization (ATU) of sofosbuvir, a new drug against HCV developed by Gilead, opens in France on October 17. However, it is limited to situations of pre-and post-liver transplant, while the laboratory dramatically restricted access to the drug under the nominative ATU.

Sought for months by collective TRT-5 (which AID is a member) and the group of viral hepatitis (CHV), this cohort ATU has finally opened, as expected, there is a few days. However, despite the association pressure and the desire of the French drug agency (which he said she lengthy negotiations with the laboratory broader criteria), it is clear that access is restricted to persons in the emergency treatment of extreme situation.

In fact, can only benefit from the new drug people "on the waiting list for a liver transplant and require treatment to prevent re-infection with HCV," or "underwent liver transplantation and have a recurrence of infection with HCV, aggressive, resulting in a worsening of liver disease with a life expectancy of less than 12 months in the absence of treatment. " It is the physician of the person making the request of ATU. The ATU is open to people co-infected HIV / HCV.

Protocol for therapeutic use ...

The "protocol for therapeutic use and information collection" is downloadable on the website of the National Security Agency of the drug (MSNA). It provides that, in the context of this ATU, the sofosbuvir (400 mg, 1 tablet daily, with or without food) is used in combination with ribavirin (1000-1200 mg) and pegylated interferon if its use is possible (it is against-indicated in patients with decompensated cirrhosis). Pre-transplant treatment is until liver transplantation without exceeding 11 months (48 weeks) of treatment. If relapse occurs before transplantation, a restatement may be considered. Post-transplantation, the treatment is for 6 months (24 weeks).

... And information gathering

If the first goal of the ATU is to save lives, the collection of information set up is very useful, both to evaluate the effectiveness in these difficult people to deal with the importance of adverse effects. And, as for the person himself than for other patients. The MSNA has also worked with the ANRS (National Agency for Research on AIDS and Viral Hepatitis) to set up an additional collection of information through the cohort CUPILT. The inclusion in this cohort will be offered to people receiving ATU.
The price of the drug in the context of this cohort ATU has not yet been reported by the laboratory.

What interactions?

According to the summary of product characteristics, we know that the particular sofosbuvir can be used without dose adjustments with:
● the following anti-suppressing drugs: cyclosporine (carefully) and tacrolimus
● methadone (opioid substitution treatment) ,
● the following anti-HIV drugs: efavirenz (Sustiva), emtricitabine and tenofovir (Truvada), rilpivirine (Edurant, Eviplera), darunavir / ritonavir (Prezista / Norvir), raltegravir (Isentress).
However, it should not be used with products containing St. John's wort, a plant sometimes used in the treatment of mild to moderate depression and mood disorders.

Nominative ATU

For people who do not fall within the criteria of the cohort ATU, but the treatment can not be delayed, the doctor can make a nominative ATU request from the MSNA.

Unfortunately, despite pressure from associations, on the hundred nominative ATU requests granted, the Gilead has actually supplied the product to a third of people, systematically refusing to cirrhotic individuals. And even though the emergency treatment and the possibility of a real clinical benefit status had yet been validated by the MSNA.

Enough to arouse the anger of the TRT-5 and CHV which launched at the beginning of the summer, a petition that gathered more than 850 signatures. But the firm, between the decisions of experts convened by the public agency, of its own experts, remained deaf to this request, endangering the health or life of many people.

The AMM expected in January

Meanwhile, drug evaluation is well underway. In the United States, the drug has received a positive opinion on October 25 experts from the Food and Drug Administration (unanimously), the U.S. marketing authorization is expected on December 8. In Europe, after an expedited review procedure, the decision of the experts from the European Medicines Agency (EMA) is expected for November 6, for a European marketing authorization should be formally granted by the European Union in January 2014.

Therefore, the product should be available soon for those falling within the scope of the marketing authorization and do not have appropriate therapeutic alternative. However, the new legislation, introduced in the bill funding the 2014 social security could delay access. In its initial version, the section 39 restricted access, despite the issue of the marketing, to situations of ATU established before the AMM until the final redemption price was not published in the "Official Gazette" , which takes an average of one year. The version finally adopted Friday by the National Assembly, under pressure from AIDS, the CISS (interassociative Collective Health), TRT-5 SOS Hepatitis and AFM-Telethon, discusses the criteria of MA, which is a half-victory. However, it states that the lack of appropriate alternative therapy should be assessed by the Authority for Health (HAS), without specifying a time limit for rendering the decision. Which, given the usual time decision venerable institution is somewhat disturbing. The examination of the text will be in the Senate from 12 November 2013.

Country: France

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