Tenofovir: FDA Hearing October 3, Public Comment Deadlines September 26.

On October 3 the FDA's Antiviral Drugs Advisory Committee will hold a public hearing on tenofovir (full chemical name tenofovir disoproxil fumarate, or tenofovir DF; new brand name Viread[TM]), an antiretroviral developed by Gilead Sciences and currently in pre-approval expanded access. Public comments are scheduled for the October 3 hearing, and written statements can also be submitted. Both written comments, and sign-up to make an oral presentation, are due at the FDA by September 26. Details are included in the official announcement below.

[Name and drug class: The full chemical name of tenofovir is tenofovir disoproxil fumarate, or tenofovir DF; the new brand name is Viread[TM]. Tenofovir is a nucleotide analog -- differing from the nucleoside analogs (AZT, d4T, etc.) in that it requires less processing within cells, and therefore is active in certain cells where the nucleoside analogs generally are not. Both nucleotide analogs and nucleoside analogs are reverse transcriptase inhibitors.]

On the following day, October 4, the same Advisory Committee will discuss another drug, voriconazole, for severe fungal infections.

Comment

Tenofovir is an important new HIV treatment because of its resistance profile, potency, apparently low side effects, and ease of use. The Committee is expected to recommend it for approval. (The FDA does not have to follow the recommendation of an Advisory Committee, but it almost always does.)

A likely issue before the Committee will be whether to recommend a broad indication (such as "indicated in combination with other antiretroviral agents for the treatment of HIV infection"), or a narrow one that would limit the drug to advanced patients, where more data is available. In either case physicians would legally be permitted to prescribe the drug for any patient, but insurance reimbursement will often be a problem if the drug is labeled only for treatment-failure cases and physicians want to use it earlier. We believe that approval with a broad indication is important for several reasons:

* Tenofovir has already been shown to work well for advanced HIV patients, the most difficult to treat. While less information is available today for its use early in treatment, everything we know about antiretrovirals suggests that they work at least as well when used early in treatment, and with at least as good a safety profile.

* Many patients cannot tolerate existing regimens because of metabolic or other side effects. Their physicians may want to try changing their regimen early, for example when lipoatrophy (fat wasting) first begins to develop, to prevent longterm harm. Even though much remains unknown about metabolic side effects and how to manage them, doctors and patients should have more options to try if necessary, without having to fight HMO red tape or pay for necessary drugs out of pocket.

* Some doctors are moving toward using stronger drug combinations first, instead of keeping them in reserve for when the other treatments fails -- and the patients have become more difficult to treat. Medical opinion is still largely unformed on this issue; no one knows for sure which strategy is better, and in practice we will probably learn from clinical experience before we learn from clinical trials. Reimbursement obstacles should not block clinical practice and experience.

* Adherence remains crucial, and is improved by regimens that are easy to take. Tenofovir is taken as one tablet once a day, so it can be a part of once-daily regimens, important for patients with adherence difficulties and also for tests of directly observed therapy.

* It has been hard to get companies to research new drugs for advanced patients. Most prefer to test their drugs earlier when it is usually easier to show viral-load changes and lack of side effects. Gilead did test tenofovir first in late-stage patients, and if it is punished with a restrictive label, other companies will become even more reluctant to test early for advanced patients, who need new options the most. (Gilead is now running a large trial, called Study 903, for treatment-naive patients, but data will not be available until 2002.)

One can never be sure what will come out of an advisory committee -- especially when the FDA has been under increasing pressure in recent years to be more conservative in its drug approvals. We hope HIV physicians will write or speak to the Committee about their need for new treatment options -- and tell the Committee and the FDA what labeling for tenofovir would be best.

FDA Meeting Announcement, Distributed August 21:

The Food and Drug Administration (FDA) will hold a public meeting of the Antiviral Drugs Advisory Committee on October 3 and 4, 2001, 8:30 a.m. to 5 p.m. at the Town Center Hotel, Maryland Ballroom, 8727 Colesville Road, Silver Spring, MD. For directions, or information about lodging, please call the hotel directly at [phone].

On October 3, 2001, the committee will discuss new drug application (NDA) 21-356, for Viread[TM], (tenofovir disoproxil fumarate) Tablets, proposed for the treatment of Human Immunodeficiency Virus (HIV) infection. The sponsor is Gilead Sciences, Inc.

Additionally, on October 4, 2001, the committee will discuss new drug application (NDA) 21-266, for Vfend[TM] (voriconazole) Tablets, and (NDA) 21-267, Vfend[TM] I.V. (voriconazole) for Infusion, Pfizer Global Research and Development, proposed for the treatment of invasive aspergillosis, serious Candida infections, infections caused by Scedosporium spp. and Fusarium spp., rare and refractory infections and empirical treatment.

This meeting is free and open to the public. No prior registration is required to attend.

Interested persons are encouraged to present data, information, or views, orally or in writing, on issues pending before the committee.

If you would like to make an oral presentation, please send the following information to: Tara Turner, Pharm.D., Center for Drug Evaluation and Research (HFD-21), 5600 Fishers Lane, Lane (for express delivery: 5630 Fishers Lane, rm. 1093)Rockville, MD 20857, by FAX at 301-827-6776, or by e-mail to TurnerT@cder,fda.gov by September 26, 2001.

* Name of speaker (and organization/affiliation if appropriate)

* Address, phone and FAX numbers

* A brief summary statement of your comments

* Approximate amount of time you would like to speak

Oral presentations from the public are scheduled on both days between approximately 1 p.m. and 2 p.m. Time allotted for each presentation may be limited, depending on the number of speakers.

Written submissions may also be sent to Dr. Turner by September 26, 2001.

Please call the FDA Advisory Committee Information Line, 1-800-741-8138 (301-443-0572 in the Washington, DC area), code 12531, for up-to-date information on this meeting.