Two weeks after an advisory panel recommendedapproval of BioChem Pharma's lamivudine (3TC) for usein combination with zidovudine (AZT) for treatment ofHIV, the FDA cleared the new AIDS drug for marketingMonday.
The AZT-3TC combination is only the second first-linetherapy approved for HIV in the U.S. AZT, which ismade and sold by Glaxo Wellcome Inc., of ResearchTriangle Park, N.C., was the first AIDS drug approved in1987. Glaxo also will manufacture and sell 3TC, whichwas licensed from BioChem Pharma, of Laval, Canada.Biochem Pharma will receive royalties.
In addition to its quick action, the FDA approved a broadlabel for the combination therapy, allowing for earliertreatment of HIV by not tying cost reimbursement formedication to CD4 cell counts.
The stocks of both BioChem Pharma(NASDAQ:BCHXF) and Glaxo (NYSE:GLX) advancedMonday. BioChem Pharma closed up $1.25 to $37 andGlaxo, a subsidiary of London-based Glaxo Holdings plc,ended the day 50 cents higher at $27.75.
"The approval features by far the biggest label [for atherapy] in HIV," said Timothy Wilson, a biotechnologyanalyst for UBS Securities Inc. in New York. "There areno limits on CD4 counts. It paves the way for earliertreatment."
The decrease in number of CD4 cells reflects HIV'sweakening of the immune system. When CD4 countsdecline to 200 the onset of AIDS is diagnosed. A healthyperson has CD4 counts of 2,000.
While AZT is prescribed after CD4 counts slip below500, the 3TC-AZT combination can be used when anHIV patient's CD4 counts begin decreasing and viral loadincreases. According to the label, the drugs can be used"based on clinical and/or immunological evidence ofdisease progression."
"The earlier the treatment, the more effective thetreatment," said Ed Hurwitz, an analyst with RobertsonStephens & Co., in San Francisco. "You can reduce viralloads and have a healthy immune system able to clear thevirus."
Ramona Jones, spokeswoman for Glaxo, said 3TC will bein drug stores within a week. A year's worth of 3TC forone patient will cost $2,270 wholesale. AZT's wholesalecost is between $2,300 and $2,800 per patient annually.Jones said worldwide sales of AZT for the first sixmonths of 1995 were $152 million. 3TC has not yet beenapproved outside the U.S. Glaxo sells AZT as Retrovirand will market 3TC as Epivir.
The 3TC-AZT combination was recommended forapproval Nov. 6, 1995, by the FDA's Antiviral DrugsAdvisory Committee based on studies showing thatpatients sustained higher CD4 counts with both drugsthan with either one alone. (See BioWorld Today, Nov. 7,1995, p. 1.)
While CD4 counts are used as a marker for the drug'seffectiveness, Glaxo is conducting other studies todetermine the clinical benefit of 3TC on patient survivaland progression of the disease.
Both 3TC and AZT are nucleoside analogs that attackreverse transcriptase, the enzyme that makes it possiblefor HIV to replicate. However 3TC also has demonstratedit can slow HIV resistance to drugs. One of theshortcomings of AZT is HIV's ability to mutate quicklyand resist the drug's effect. Data from clinical studiesshowed 3TC, in some cases, reversed resistance to AZT.
"3TC is to AZT what `Pulp Fiction' is to John Travolta,"said Wilson. "It's gives AZT a second career."
Hurwitz said the FDA's approval of a 3TC-AZT therapysignals an end to single drug treatment for HIV. And with3TC's ability to combat the virus' drug resistance, itcould become the "centerpiece" of most combinationtherapies.
Wilson observed that 3TC already is being tested incombination with protease inhibitors, which are amongthe newest HIV drugs poised to enter the market.
Wilson also noted that 3TC has minimal side effects withmost of the toxicity in the combination therapy caused byAZT. Among the adverse events associated with the twodrugs are nausea, fatigue, diarrhea, neuropathy, low whiteblood cells and anemia. n
-- Charles Craig
(c) 1997 American Health Consultants. All rights reserved.