WASHINGTON, Dec. 7, 1995 -- The Food and Drug Administration today approved the first protease inhibitor, a new class of therapy for the treatment of advanced HIV infection. Saquinavir, the new drug, received approval for use in combination with older nucleoside analogue medications only three months after the agency received the application for its marketing.

"This is some of the most hopeful news in years for people living with AIDS," said HHS Secretary Donna E. Shalala. "Today's approval introduces a new class of drugs for treating AIDS. This drug was approved in just 97 days - evidence that FDA is carrying through on the Clinton Administration's priority to review new drugs, especially the most promising new drugs, on the fastest possible track consistent with safety."

Commissioner of Food and Drugs David A. Kessler, M.D., pointed out that five of the six AIDS therapies approved so far were reviewed in six months or less.

"The review of saquinavir is the fastest approval of any AIDS drug so far, and demonstrates FDA's flexibility in situations when saving time can mean saving lives," Kessler said. "When it comes to AIDS and other life-threatening diseases, we have learned to take greater risks in exchange for greater potential health benefits."

Both protease inhibitors and nucleoside analogues chemically inhibit replication of the human immunodeficiency virus, although at different points in the replication process. Nucleoside analogues include the already-approved anti-HIV drugs AZT, ddC, ddI, d4T and 3TC.

The agency based its approval of saquinavir on clinical trials comparing three drug combinations in more than 900 HIV-infected individuals: saquinavir with AZT, saquinavir with ddC, and saquinavir with both AZT and ddC. The primary measure of drug effect was changes in patients' CD4 cell counts, an indication of immune system strength. (values greater than 800 per milliliter of blood are normal in healthy individuals.)

Over 16 weeks of treatment, CD4 cell counts increased an average of 30 to 40 cells above entry levels in patients on saquinavir in combination with ddC or AZT or AZT plus ddC. Effects were attributable to combinations of saquinavir and a nucleoside analogue to which a patient had not been previously exposed. Saquinavir doses of less than 600 mg three times a day did not produce increases in CD4 cell counts. The duration of CD4 cell increases is not fully determined, although in general it lasted for at least the 16 weeks of the trials.

Few adverse events were associated with saquinavir, and for most patients the drug was well tolerated.

FDA's approval of the saquinavir marketing application was granted as an accelerated approval, a regulatory mechanism under which the agency bases early approval for a product on laboratory markers such as CD4 cell counts, rather than on clinical endpoints such as delay in death or reduction in opportunistic infections.

FDA may withdraw the approval of products granted accelerated approval if post-marketing studies fail to verify clinical benefits. Trials designed to demonstrate clinical benefits of saquinavir in combination with other nucleoside analogues are ongoing.

Saquinavir is manufactured by Roche Laboratories under the trade name Invirase.

Antiretrovirals Currently Approved
For HIV Infection and AIDS-Related Conditions

Product               Approval                    Review Time
To Approval


Retrovir (AZT)        March 1987                  3.5 months

Videx (ddI)           October 1991                6 months

Hivid (ddC)           June 1992                   8.5 months

Zerit (d4T)           June 1994                   6 months

Epivir (3TC)          November 1995               6 months

Invirase (saquinavir) December 1995               3 months


Dates of Approval:  Invirase (Saquinavir)

Dates of Approval by U.S., France, Germany and U.K.

U.S.             December 1995

France           (not yet approved)

Germany          (not yet approved)

United Kingdom   (not yet approved)


Dates of Approval:  Epivir (3TC)

Dates of Approval by U.S., France, Germany and U.K.

U.S.             November 1995

France           (not yet approved)

Germany          (not yet approved)

United Kingdom   (not yet approved)


Dates of Approval:  Zerit (d4T)

Dates of Approval by U.S., France, Germany and U.K.

U.S.             June 1994

France           (not yet approved)

Germany          (not yet approved)

United Kingdom   (not yet approved)


Dates of Approval:  ddC (Hivid)

Dates of Approval by U.S., France, Germany and U.K.

U.S.             June 1992

France           January 1994

Germany          January 1994

United Kingdom   September 1994


Dates of Approval:  ddI (Videx)

Dates of Approval by U.S., France, Germany and U.K.

U.S.             October 1991

France           May 1992

Germany          August 1992

United Kingdom   February 1994


Dates of Approval:  Retrovir (AZT)

Dates of Approval by U.S., France, Germany and U.K.

U.S.             March 1987

France           March 1987

Germany          April 1987

United Kingdom   March 1987


Other Products Currently Approved
For HIV Infection and AIDS-R Conditions

Interferon A          Dronabinol

Ganciclovir           Megestrol Acetate

Fluconazole           Trimetrexate

Pentamidine           Clarithromycin

Erythropoietin        HIVIG

Foscarnet             TMP/SMX

UItraconazole          Doxorubicin

Atovaquone            Amphotericin B

Rifabutin


Expanded Access Enrollment

Drug              Dates          # Enrolled

AZT              1986-87           4,804

trimetrexate     1988-94             753

pentamidine      1989                728

ddI              1989-91         >21,000

ddC              1990-92           6,705

atovaquone       1991-93           1,054

rifabutin        1992-93           2,506

d4T              1992-94          12,551

3TC              1993-95          29,430

saquinavir       1995              2,200

indinavir        1995              1,500


FDA ON THE INTERNET:  http://www.fda.gov/

CONTACT: Arthur Whitmore of the Food and Drug Administration, 301-443-3285, or home, 202-547-4961