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Gilead Begins Single Pill Hepatitis C Study for 2014 Approval
  Bloomberg, By Michelle Fay Cortez and Ryan Flinn on July 27, 2012

Gilead Sciences Inc. (GILD) (GILD) said it plans to start a combination study of two drugs in a single pill to treat hepatitis C by the end of the year, putting it on track to request U.S. regulatory approval for the medicine in 2014.

Gilead, which spent $10.8 billion to acquire one of the medicines, GS-7977, plans to combine it with another, GS-5855, in a trial of 800 patients starting in the fourth-quarter, said Norbert Bischofberger, chief medical officer of the Foster City, California-based company, in a conference call yesterday. If the combination is effective, the company could apply for regulatory approval in the middle of 2014, Bischofberger said.

Gilead is among several drugmakers racing to develop new hepatitis C treatments that act more quickly with fewer side effects than the current standard of care. The goal is to provide doctors and patients with simpler, more effective treatments, Bischofberger said.

The company aims for a therapy that "will clearly be a one pill, once daily, maybe a 12 week course," for patients with all different types of hepatitis C, Bischofberger said. "That's our goal. We are very close."

Conventional therapy combines ribavirin with interferon, an injected immune-boosting protein that can cause flu-like side effects, for as long as 48 weeks.

Gilead is competing with Abbott Laboratories, Bristol-Myers Squibb Co., Johnson & Johnson, Merck & Co. and Vertex Pharmaceuticals Inc. (VRTX) (VRTX) to develop a new generation of hepatitis C treatments. Rising deaths among baby boomers from hepatitis C prompted U.S. health officials to declare in May that the entire age group is at risk and should be tested for the disease.

Previous Studies

Another study of GS-7977, given with ribavirin, found nine of nine patients who were previously untreated had a sustained response to the drug, with no signs of virus in their bodies after finishing the therapy. A second study, however, found just 53 percent of patients had a similar benefit, a difference the company is still trying to figure out, Bischofberger said.

Gilead, the world's biggest maker of AIDS drugs, yesterday reported net income fell (GILD) 4.6 percent in the second quarter to $711.6 million, or 91 cents a share, from $746 million, or 93 cents, a year earlier. Earnings, excluding one-time items, of 99 cents a share beat the 95 cents a share average of 25 analyst estimates compiled by Bloomberg. Revenue jumped 13 percent to $2.41 billion, the company said in a statement yesterday.

Gilead shares rose (GILD) 2.6 percent to $53 at 5:46 p.m. in New York, after closing yesterday up less than 1 percent at $51.68. The stock has gained 23 percent in the past 12 months.

Gilead press release:

In April, Gilead announced interim data from the Phase 2 ATOMIC study examining a 12-week course of treatment with the investigational once-daily nucleotide GS-7977 plus pegylated interferon and ribavirin (RBV) in treatment-naive patients with genotype 1 chronic hepatitis C virus (HCV) infection. The study found that 90 percent of patients achieved a 12-week sustained virologic response (SVR12), defined as maintaining undetectable viral load 12 weeks after the completion of therapy. These findings were presented at the 47th Annual Meeting of the European Association for the Study of the Liver (EASL) in Barcelona, Spain.

Also in April, Gilead announced interim data from the Phase 2 ELECTRON study examining GS-7977 plus RBV in treatment-naive patients with genotype 1 chronic HCV infection. Of the 25 patients who completed 12 weeks of treatment, 88 percent achieved a four-week sustained virologic response (SVR4). Three patients experienced viral relapse. These findings were presented at EASL.

Lastly in April, Gilead announced interim results from the Phase 2 QUANTUM study examining a 12-week duration of GS-7977 plus RBV in treatment-naive 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. At the four-week post-treatment time period, data were available for 17 genotype 1 patients. Of these, 59 percent achieved SVR4 and 41 percent experienced viral relapse. Additionally, seven of the patients who reached the eight-week post-treatment time period, and who achieved SVR4, remained HCV RNA undetectable.

Gilead issued earnings yesterday, from Gilead conference call:

Norbert W. Bischofberger

My remaining comments will focus on hepatitis C, where progress has been rapid.

At the EASL conference earlier this year, data were disclosed from 2 Phase II studies of a 12-week, 12-week course of GS-7977 and Ribavirin in genotype 1 infected treatment-naïve patients. In the ELECTRON study, the SVR4 rate in genotype 1 naïve patients was 88% or 22 out of 25 patients and in the QUANTUM study, the SVR4 rate in genotype 1 treatment-naïve patients was 53% or 10 out of 19 patients.

I would now like to provide an update on new data from 2 Phase II studies evaluating 24 weeks of treatment with GS-7977 and Ribavirin, in treatment-naïve genotype 1 infected patients.

In the QUANTUM study, 19 genotype 1 patients were randomized to receive 24 weeks of GS-977 and Ribavirin. Of those 19 patients, 10 were 53% achieved in SVR4.

The second trial is conducted by the NIAID, in a cohort of genotype 1 infected predominantly African-American patients, a population which has historically been more difficult to treat.

In that study, of the first 9 patients who completed 24 weeks of treatment with GS-7977 and Ribavirin all 9 or 100% achieved SVR4.

These results from the QUANTUM and the NIAID studies are included in Slides 31 and 32 of earnings slide deck.

In summary, in the various Phase II cohorts, treatment with GS-7977 and ribavirin for 12 or 24 weeks was in genotype 1 infected patients, resulted in SVR4 rates between 53% and 100%.

In May and June of this year, discussions were held with the U.S. FDA and 3 European regulatory agencies, and agreement has been achieved on a comprehensive Phase III development plan for GS-7977 and on a Phase III plan for GS-7977 in combination with the NS5A inhibitor, GS-5885.

The initial NDA and MAA filings will be for GS-7977 and will include data from 4 Phase III studies, 3 conducted in genotype 2/3 infected patients and 1 in genotype 1 infected patients.

The 3 genotype 2/3 studies are FISSION, POSITRON and FUSION. FISSION is the first study in 500 genotype 2/3 naïve patients, comparing 12 weeks of treatment with GS-7977 and Ribavirin to the current standard of care of 24 weeks of treatment with peg-interferon Ribavirin.

The second study, POSITRON, is comparing 12 weeks of treatment with GS-7977 and Ribavirin in 240 genotype 2/3 interferon intolerant or ineligible patients to placebo.

And thirdly, FUSION is a study in 200 genotype 2/3 treatment experienced patients exploring 12 or 16 weeks duration of treatment with GS-7977 and Ribavirin.

And all 3 trials, FISSION, POSITRON and FUSION are now fully enrolled. And the last patient in these studies has started dosing just today.

A fourth Phase III study called NEUTRINO is a single arm study evaluating a 12-week course of GS-7977, peg-interferon and Ribavirin in 300 genotype 1, 4, 5 and 6 infected patients.

Screening in the NEUTRINO study is completed and the last patient should start dosing by mid-August.

This same regimen, 12 weeks of GS-7977, peg-interferon, ribavirin, was evaluated previously in genotype 1 patients in a Phase II study, called ATOMIC and resulted in SVR4 rate of 92%.

These Phase IV, Phase III studies are outlined on Slides 33 and 34 in our earnings slide deck.

With these 4 Phase III studies underway, we anticipate being able to file for regulatory approvals for GS-7977 by the middle of next year.

If successful, the initial indication will for 12 to 16 weeks of treatment with GS-7977 and Ribavirin in genotype 2/3 infected patients, and for 12 weeks of treatment with GS-7977, peg-interferon and Ribavirin in genotype 1, 4, 5 and 6 infected patients.

In PEMARON [ph], we're also advancing GS-7977 in combination with GS-5885 for the treatment of genotype 1 infected patients.

GS-7977 and GS-5885 were successfully co-formulated into a single pill, fixed dose combination. The IND on this fixed dose combination was filed a month ago and the Phase I study evaluating the bioavailability was initiated last week.

If the Phase I data show that the fixed dose combination results in adequate exposures of GS-7977 and GS-5885, we expect to initiate the Phase III study with this fixed dose combination in the fourth quarter of this year.

This Phase III study is planned as a forearm randomized trial in 800 patients, evaluating the fixed dose combination with or without Ribavirin for either 12 or 24 weeks in treatment-naïve genotype 1 infected patients.

The study will contain an interim futility analysis after the first 200 patients or 50 per arm have been enrolled, an independent data, safety monitoring board will evaluate the SVR4 rates of the 12-week treatment arms.

If the predefined response rates are met, then the remaining 600 patients will be subsequently enrolled.

At the time of this interim analysis, additional data will be available from the ELECTRON study on 12 weeks of treatment with GS-7977 and GS-5885 and Ribavirin in genotype 1 null responders and genotype 1 naïve cohorts, as well as 12-week data from the ongoing BMS study of GS-7977 and Daclatasvir with or without Ribavirin.

All these data will allow us to decide on the design of the second confirmatory study supporting the filing of GS-7977, 5885 fixed dose combination.

If treatment of genotype 1 infected patients with the fixed dose combination GS-7977, 5885 for 12 weeks, results in acceptable high SVR4 rates, then the second confirmatory study could be initiated in the first half of 2013.

The fixed dose combination regulatory filings could, in that case, follow the initial GS-7977 filings a year later by mid-2014.

The development strategy for the GS-7977, GS-5885 fixed dose combination is outlined in Slide 36 of our slide deck.

In summary, a number of programs had been advanced across therapeutic areas. GS-7340 co-formulated in 2 single tablet regimens is advancing in Phase II. GS-1101 is advancing in Phase III and notably, 4 Phase III studies evaluating GS-7977 in genotype 1 through 6 HCV infected patients are fully enrolled and the NDA, MAA are on track to be filed by the middle of next year.

Finally, we plan to advance the fixed dose combination of GS-7977 and 5885, currently in Phase I clinical testing, into Phase III in the fourth quarter of this year.







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