WASHINGTON _ A skeptical advisory committeeMonday recommended that the FDA approve thenucleoside analog 3TC as part of a combination therapyfor first- line treatment of HIV infection.
If the agency takes the panel's advice, it would be the firstnew initial treatment for HIV since AZT.
On the first day of a marathon three-day session toconsider new antiviral AIDS treatments, the AntiviralDrugs Advisory Committee took 10 hours to produce avote: seven members favored the recommendation andone abstained from Glaxo Wellcome Inc.'s request foraccelerated approval of Epivir (3TC) used in combinationwith zidovudine (AZT).
The committee agreed that the combination approachrepresents a significant improvement over AZTmonotherapy even though several committee membersraised questions about Glaxo's use of data from anexpanded access program to qualify for the acceleratedaccess.
Biochem Pharma Inc., of Laval, Quebec, discovered 3TCin 1989 and later licensed rights to Glaxo, the London-based pharmaceutical company that bought out Wellcomeplc earlier this year to give itself a leading position in theHIV market. Wellcome owned AZT, or Retrovir. It'sbeen just six months since the company filed a new drugapplication.
Biochem Pharma's stock (NASDAQ:BCHXF) hasclimbed steadily this year, a sign investors were confidentthat Monday's news would come as no surprise. It closed1994 at $10.37 per share. When the company submittedits new drug application in July, the stock was at $21.63.On Monday, it closed at $40.50, up $1.63. News of thepanel's decision was released after the market closed.
The committee was nudged in favor of acceleratedapproval by a series of public statements made by FDACommissioner David Kessler highlighting the need fortreatment options for AIDS patients. Advisory committeeexecutive secretary David Feigal made it clear before thecommittee started its deliberations that the agency "waschanging the basic rules about accelerated approval fordrug development."
Previous requests for accelerated approval involvedtherapies that represented improvements over existingones, Feigal said. But the three-day meeting of theantiviral committee would deal with applying acceleratedapproval more broadly "to look at evidence fromconfirmatory trials to show clinical benefit and toconsider the needs of the patient population which maybe intolerant to existing therapies and for whom no drugsare available."
Feigal's statement was questioned by several committeemembers, particularly Alexander Shepard, a clinicalpharmacologist , of the University of Texas. who saidrepeatedly that he was "driven by the data and the FederalRegister regulations on accelerated approvals." Hedeclined to support accelerated approval "because thecompound has not been compared to other therapies andnot proven to be better."
Panel chairman Fred Valentine, professor of thedepartment of medicine at New York University MedicalCenter, admitted to committee skeptics that, "thisapplication makes us think about accelerated approval ina new and broader way." However, because most of theskeptics were nonvoting members of the panel, theapplication easily cleared the committee.
Opposition to the application seemed to subside afterassurances were made both by FDA officials and Glaxothat confirmatory clinical trials would be performed in apediatric population that would be extrapolated to adultpatients. The advisory panel had been disturbed byreports from Glaxo that up to 15 percent of all pediatricpatients developed pancreatitis and sought additionalexperience data about the drug in younger patients.
Last February, details of Phase II and III studies revealedthat 3TC and AZT, given together suppress HIV activity;increase the blood's supply of critical CD4 cells, whichare decimated by HIV; and prolong AZT's antiviralactivity _ even after the emergence of resistance to both3TC and AZT. (See BioWorld Today, Feb. 2, 1995, p. 1.)
Like AZT, 3TC is a nucleoside analog that attacks reversetranscriptase, the enzyme that makes it possible for HIVto copy itself.
While the committee agreed that the combination therapyshould be made available as an initial therapy because itappeared to improve the long-term effectiveness of AZT,it urged the FDA to restrict the labeling to patients withCD4 cell counts above 250 because Glaxo hadaccumulated evidence only in these patients.
The advisory committee adjourned to shouts from theaudience that approving Glaxo's accelerated approvalrequest "had sold out the community" and made "nocoherence [with] the regulations."
Glaxo has worldwide rights, excluding North America, todevelop, manufacture and sell 3TC. An equally ownedjoint venture will commercialize 3TC in Canada. And inthe U.S., Glaxo will be the exclusive distributor. n
-- Michele L. Robinson Washington Editor
(c) 1997 American Health Consultants. All rights reserved.