NUTLEY, N.J. -- Hoffmann-La Roche Inc. said Monday that itshipped its first HIVID anti-AIDS drug over the weekend, a dayafter the FDA approved the use of HIVID (ddC) in combinationwith the already-approved Retrovir for treatment of advancedHIV infection.
The combined Retrovir (zidovudine), also known as AZT, madeby Burroughs Wellcome Co., and Roche's HIVID (zalcitabine),becomes the third treatment option against AIDS, joiningstand-alone Retrovir and ddI, made by Bristol-Myers Squibb.HIVID-Retrovir was the first drug approval under the FDA'saccelerated review process.
"Combination therapy with HIVID and zidovudine is a majoradvance in the treatment of HIV infection," said Margaret A.Fischl, director of the comprehensive AIDS program at theUniversity of Miami School of Medicine and a professor ofmedicine. "The data from a small study have shown thatcombination therapy was well-tolerated and that the sideeffects were no different than we would have anticipated witheither drug alone."
The wholesale price of a patient's one-year supply of HIVIDwas set at $1,826, according to Hoffmann-La Roche, the U.S.affiliate of the Swiss-based Roche Holding Co. Ltd. It alsoannounced two programs to assist patients unable to afford thedrug at the listed price.
The actual cost to patients of the combination therapy will behigher and does not include the costs of Retrovir, which has anannual wholesale price of $3,159 for a daily dosage of 600milligrams, according to Roche.
HIVID works by inhibiting the action of reverse transcriptase, aviral enzyme that is critical in the replication cycle of HIV,which causes AIDS. HIV replicates by infecting the body's Tcells, which play important roles in the immune system. WhenHIVID is present in the cell, it binds to reverse transcriptaseand prevents the virus' genetic material from binding to the Tcell's genetic code.
"HIVID can prevent healthy T cells from becoming infected,"said Whaijen Soo, Roche's assistant vice president and seniordirector of clinical virology and AIDS research. "But once thecell is infected with the AIDS virus, HIVID cannot stop theprogression of the disease."
It is similar in action to ddI and also has some of the same sideeffects, said Darien Wilson, senior associate of public affairs atRoche. The major toxicities with HIVID are peripheralneuropathy, or tingling or pain in the arms and legs. Moderateor severe reactions appeared in 17 percent to 31 percent ofpatients treated with HIVID alone. Pancreatitis appeared infewer than 1 percent of patients treated with HIVID alone, asmaller incidence than with ddI, Wilson said.
It is still unknown if the incidence of peripheral neuropathywill increase with the combined therapy, compared with HIVIDalone, Roche said.
About 10,000 people have been treated with HIVID throughthe course of Roche's clinical trials and its expanded accessprogram to reach patients who desire treatment but are notenrolled in a clinical trial.
Roche abandoned HIVID as a proposed stand-alone treatmentfor AIDS last December, after studies indicated that it could notimprove on Retrovir.
However, limited data from two small studies indicated thatHIVID in combination with Retrovir appeared to increase levelsof CD4 cells in AIDS patients. Elevated CD4 cell counts mayindicate that the body's disease-fighting capability has beenstrengthened. The FDA approved the combined treatment onlyfor adult patients whose CD4 cell counts have dropped below300 per cubic millimeter.
No study data has yet shown a clinical benefit resulting fromthe combination HIVID-Retrovir therapy, such as an improvedsurvival rate or lower incidence of opportunistic infections,Roche said.
Roche last October submitted data from a small combinationsafety trial that started in 1989, showing that CD4 cell countswere higher and more sustained in patients treated withcombined therapy than were the counts from a study ofpatients using Retrovir alone, Roche said.
Similar results of higher CD4 cell counts using a combinedtherapy were reported in April in data gathered by Retrovir'sdeveloper, Burroughs Wellcome. An FDA advisory committeeon April 20 recommended approval of the combined HIVID-Retrovir treatment. Although Burroughs has no formalrelationship with Roche on AIDS drugs, researchers from bothcompanies have shared some clinical data, said Roche's Wilson.
Six studies of combined Retrovir-HIVID therapy are ongoing,Roche said.
HIVID is marketed by Roche Laboratories, a prescription drugdivision of Hoffmann-La Roche, which was selected in 1987 bythe U.S. government from among 30 companies to develop ddC.The drug was synthesized by Jerome Horwitz of the MichiganCancer Foundation in 1967, and its anti-AIDS potential wasdiscovered in 1985.
-- Ray Potter Senior Editor
(c) 1997 American Health Consultants. All rights reserved.