Gilead Sciences Inc. on Thursday filed a new drug application with the FDA for a hepatitis B drug expected to capture a sizeable portion of the market.
The product, known as adefovir dipivoxil, is a nucleotide analogue that works by blocking the hepatitis B virus (HBV) DNA polymerase, an enzyme responsible for replicating the virus. Foster City, Calif.-based Gilead has not selected a trade name for the once-daily oral drug indicated for chronically ill patients who are treatment-na ve or experienced.
Gilead requested six-month priority review status based on an unmet need, Amy Flood, company communications manager, told BioWorld Today. The FDA is compelled to notify the company in 60 days whether it receives such status.
Gilead’s stock (NASDAQ:GILD) closed Friday at $37.31, down $1.14.
If cleared for marketing, adefovir dipivoxil will compete with Intron A (interferon alpha), sold by Schering-Plough Corp. of Madison, N.J.; and lamivudine (3TC), sold by GlaxoSmithKline plc, of London.
Gilead officials, though, believe adefovir dipivoxil has something to offer that the others lack.
“[The competitors] have pretty significant limitations in that interferon is only effective in a low number of patients and has difficult-to-tolerate toxicities,” Flood said. “Lamivudine patients develop resistance pretty quickly, rendering it ineffective. So there’s certainly a significant need.”
The general consensus among analysts indicates FDA approval by the end of the year.
Research notes prepared by John Sonnier, vice president, senior biotech analyst with Prudential Securities Inc., of Deerfield, Ill., estimates U.S. sales of $50 million in 2003, and $105 million in 2004.
Meanwhile, Thomas Dietz, an analyst with Pacific Growth Equities, of San Francisco, released a statement saying U.S. sales should reach $142 million by 2006.
Citing successful clinical trials, Flood said adefovir dipivoxil has been tested on a variety of patient populations and has been proven to be safe, compared to placebo.
Specifically, the new drug application is supported by data from Phase III studies in hepatitis B “e” antigen-positive patients, hepatitis B “e” antigen-negative patients and chronic hepatitis B patients with lamivudine-resistant HBV.
Data from a 515-patient trial (Study 437) indicated that adefovir dipivoxil in na ve chronic hepatitis B patients showed no resistance mutations. The trial met its endpoints of liver histology improvement and showed no kidney toxicity. Also, seroconversion was observed in 12 percent of patients treated with 10 mg for 48 weeks compared to 6 percent of patients on placebo. (See BioWorld Today, June 25, 2001.)
In another trial (Study 438), Gilead evaluated 185 patients and determined that treatment with a 10-mg once- daily dose for 48 weeks was associated with improvements in liver histology in 64 percent of patients who received the drug, compared to 33 percent of patients who received placebo (p=0002). (See BioWorld Today, Sept. 20, 2001.)
A week ago, the company initiated an early access program in the U.S. for hepatitis B patients with lamivudine-resistant HBV. A similar program started in July 2001 in France and has enrolled 289 patients to date. Meanwhile, similar programs are expected in Canada, Australia and Europe.
At one time, Gilead was studying adefovir dipivoxil for HIV but abandoned the plan after an FDA advisory panel voted against the product for that indication. (See BioWorld Today, Nov. 3, 1999.)
Last fall the company won FDA approval on another HIV drug, Viread (tenofovir disoproxil fumarate), a nucleotide analogue reverse transcriptase inhibitor. The once-daily drug was launched in the U.S. in October and in Europe in February.
Aside from Viread, Gilead’s other marketed products are AmBisome, for systemic fungal infections; Tamiflu, for influenza; DaunoXome, for HIV-associated Kaposi’s sarcoma; and Vistide, for AIDS-related cytomegalovirus.