FISSION Study Should Support Regulatory Approval For Gilead's Hepatitis C Drug

| About: Gilead Sciences, (GILD)

By Amit Cohen

Gilead Sciences (GILD) 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.

On Monday, Gilead announced positive top‐line results from two Phase III studies (FISSION and NEUTRINO) that involve the use of sofosbuvir in combination with other agents for use in treatment‐naïve patients infected with the Hepatitis C virus (HCV).

The FISSION study enrolled approximately 500 treatment-naïve patients with HCV genotype 2 or 3 (at a 1:3 ratio) and evaluated the safety and efficacy of 12 weeks of GS-7977 + RBV vs. 24 weeks of PEG-IFN and RBV. The primary endpoint of the trial is SVR12 (sustained viral response at week 12 after treatment is completed). FISSION was a non-inferiority trial in which the bottom end of the 95% confidence interval of sofosbuvir's SVR rate had to be within 15% of the SVR rate of PEG-IFN. With the weakest part of sofosbuvir's profile being its activity in GT 3 patients, and a 3:1 ratio of GT 3 vs GT 2 in the study, there was some chance that the noninferiority margin could have been missed. In fact, the expectations for FISSION had come down significantly after the release of POSITRON data during Q4:12. In POSITRON sofosbuvir + RBV produced SVR rates of 93% in genotype 2 patients and 61% in genotype 3 patients.

While the FISSION data were perhaps a bit below this bar, they were overall consistent. Overall 20% of patients in the study had compensated cirrhosis, and 72% had GT 3 infection. FISSION met its primary endpoint with 67% (170/253) of sofosbuvir + RBV patients achieving SVR, versus 67% in the PEG-IFN + RBV group. The 95% confidence interval for the comparison ranged from -7.5 to +8.0 percent, meeting the predefined criteria for non-inferiority. Sofosbuvir produced a 97% SVR rate in GT 2 patients, and a 56% in GT 3 patients, compared to 78% and 63% for PEG-IFN in those respective populations.

Little new information is given about sofosbuvir's side effect profile, although the press release does note that "The most common adverse events in the sofosbuvir plus RBV arm occurring in >10% of the patients were fatigue, headache, nausea, insomnia, and dizziness." 3 patients (1%) on sofosbuvir discontinued treatment due to adverse events, compared to 26 (11%) on PEG-IFN/RBV.

Conclusion: These results are highly encouraging considering sofosbuvir plus ribavirin is an all‐oral regimen that is taken for 12 weeks versus the current standard‐of‐care (24 weeks). While SVR rates were lower in this trial relative to the Phase II, there were different baseline characteristics (greater proportion of genotype 3 patients) and therefore the FISSION study should support regulatory approval. With the success of FISSION removing the biggest near-term risk to sofosbuvir's development, the results are an incremental positive for GILD.

The second study, NEUTRINO, was an open-label, multicenter study in treatment-naïve patients. The trial recruited 327 GT 1,4,5, and 6 patients, and all were dosed with 400mg sofosbuvir QD plus PEG/RBV for 12 weeks. 17% of patients had compensated cirrhosis, while 89% had GT 1 HCV. The primary endpoint of the trial is SVR. The NEUTRINO study closely reflects the design of the ATOMIC trial in which 12 weeks of sofosbuvir, pegylated interferon and ribavirin were also given. Data from ATOMIC released at the EASL meeting in April 2012 showed that 90% (47/52) of patients in the arm that received 12 weeks of sofosbuvir+PEG/RBV achieved SVR12. The NEUTRINO results were very consistent with those of ATOMIC. In NEUTRINO 90% of sofosbuvir/PEG/RBV achieved SVR, well above the historical control SVR rate of 60%. Importantly, sofosbuvir/PEG/RBV was able to achieve such a high SVR rate in GT 1 patients with only 12 weeks of dosing. Most of the side effects seem attributable to PEG-IFN/RBV and include fatigue, headache, nausea, insomnia, and anemia.

Conclusion: After 327 patients were treated for 12 weeks, the study met its primary efficacy endpoint of superiority compared with a predefined historical control SVR rate of 60% in the same patient population. Overall, this data is encouraging, especially when one considers the typical results seen with the current standard‐of‐care.

Going forward, data from one more ongoing Phase III study ((FUSION)) evaluating 12 or 16 weeks of sofosbuvir plus ribavirin in 200 treatment‐experienced patients with genotype 2/3 HCV is fully enrolled and SVR12 results are expected in the first quarter of 2013. Collectively, results from the FISSION, FUSION, NEUTRINO, and POSITRON will form the basis of Gilead's initial regulatory filing for sofosbuvir, which is expect by the middle of 2013.

Gilead Risk: Gilead's entrance into new markets, such as the cardiopulmonary space, where it is not a major player, poses a risk to the company going forward. The HCV space is also already crowded and competitive even with the acquisition of Pharmasset and comes with significant risk.

Disclosure: I have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

Additional disclosure: Big Ben Research is a group of investment professionals, and writers. This article was written by Amit Cohen. We did not receive compensation for this article, and we have no business relationship with any company whose stock is mentioned in this article. This information is not to be construed as an offer to buy or sell any security mentioned on this article. We have no positions in any stocks mentioned, and no plans to initiate any positions within the next 72 hours.