By Kim Coghill
SILVER SPRING, Md. ¿ An FDA panel Wednesday said Gilead Sciences Inc.¿s investigational antiretroviral agent for HIV demonstrates safety and efficacy in adults.
But in an ¿unofficial¿ vote on the indication, members of the Antiviral Drugs Advisory Committee of the Center for Drug Evaluation and Research were clearly split on Viread (tenofovir disoproxil fumarate), a once-daily 300-mg nucleotide reverse transcriptase inhibitor that can be administered in conjunction with other HIV drugs. Nine members supported a restricted label for use only in treatment-experienced patients, while seven members said they support a broad use, for both experienced and naove patients. Two members abstained.
The FDA makes the final decision, and is not bound by, but usually follows, the committee¿s recommendation.
John Milligan, vice president of corporate development at Gilead, said, ¿It¿s a good day for Gilead. From here, we¿ll work with the FDA on the label. Although they didn¿t include naove patients, we want to include those patients¿ in the final label.
The FDA¿s decision deadline under PDUFA is Nov. 1.
At peak sales, Viread is expected to generate about $400 million worldwide, according to Banc of America Securities in New York. Gilead does not plan to seek a marketing partner.
Many committee members were wary of supporting Viread¿s use in naove patients since the company¿s study in the indication is not complete.
This confirmatory study, known as Study 903, looks at 601 treatment-naove patients for 96 weeks. By design it compares a treatment regimen of Viread, lamivudine (3TC) and efavirenz to a treatment regimen of stavudine (d4T), lamivudine and efavirenz in a blinded fashion in patients in the U.S., Europe and South America. Study 903 is scheduled to be complete in the first quarter of 2002.
¿When there¿s nothing else available, I think this would be a good drug,¿ said Roger Pomerantz, a panel member and professor of medicine, biochemistry and molecular pharmacology at Thomas Jefferson University in Philadelphia. ¿I would recommend its use for experienced patients but not for naove patients with high viral loads.¿
Agreeing with her colleague, Sharilyn Stanley, associate commissioner of disease control and prevention at the Texas Department of Health in Austin, said, ¿We really don¿t know what the best use of this is and we don¿t know what combination it should be used for. Clearly, it is efficacious for salvage therapy [treatment-experienced patients], but I¿m very apprehensive about using it for everyone. We can put a label on it, but we can¿t control how it is used.¿
Gilead presented completed data on experienced patients. There already are about 15 drugs on the market for HIV, including lamivudine and AZT, two of the most commonly used products. According to the FDA, there was no noted cross-resistance between lamivudine and Viread.
¿We haven¿t seen enough data on drug interactions,¿ said Jonathan Schapiro, panel member and clinical assistant professor of the Department of Medicine at Stanford University School of Medicine in Stanford, Calif. ¿There are concerns, but for patients with no other options, I think this works and we should get it into the hands of people who need it.¿
In his presentation to the panel Wednesday, Norbert Bischofberger, Gilead¿s executive vice president for research and development, said clinical studies of Viread prove the medicine shows ¿no clinically significant drug interactions, good tolerability, a favorable resistance profile and a durable treatment effect.¿
Kimberly Struble, an FDA reviewer, agreed that Viread is well tolerated, but added that side effects could include vomiting, nausea, diarrhea and flatulence.
The panel reviewed Gilead¿s data from Study 907, a 48-week, 552-patient trial of treatment-experienced people with HIV. The study met its primary endpoint of reduction in viral load, and the side effects mentioned by Struble were similar in Viread patients and in placebo patients, the company said.
Gilead is seeking approval based on data from Study 907, Jay Toole, the company¿s vice president of clinical research, told the committee.
Another trial, referred to as Study 902, is a Phase II trial of 189 patients that reviewed long-term safety. The company said this study proved that Viread is associated with an adverse-event profile similar to that in the placebo group during the first 24 weeks and sustained reductions in HIV RNA in treatment-experienced patients after nearly two years of treatment.
Aside from patients participating in clinical studies, Gilead has enrolled 5,000 patients over the past several months in the expanded-access program, which allows infected people to take the product before it is approved.
Gilead also has filed for regulatory applications in the European Union and Australia.
In other business, last month Gilead said it likely will file a new drug application during the first half of 2002 for adefovir dipivoxil, a treatment for chronic hepatitis B. (See BioWorld Today, Sept. 20, 2001.)
Trading on Gilead¿s stock (NASDAQ:GILD) was held Wednesday.