Glaxo presented data on their "908" drug (formerly VX175) a version of Agenerase with a better pill burden and much improved tolerability. The trial compared 908 to nelfinavir, both in a twice-a-day regimen with abacavir and 3TC. At 24 weeks, drops in RNA and gains in CD4 counts were similar. If starting with viral load under 100,000, there was a similar likelihood of achieving VL under 400 copies. Glaxo's drug showed its modest potency edge in those who started with VL above 100,000 at baseline. Your mileage may vary.
As expected, there was three times as much diarrhea on the nelfinavir arm. Triglycerides were lower on 908, an advantage that will likely go out the window if Glaxo shoots for once-a-day boosting with ritonavir. One note: the incidence of abacavir-associated drug allergy in this study ran between 5 and 8 percent, similar to the rate in the TARHEEL study -- both higher than the 3 percent rate that Glaxo often quotes. Two other Phase III trials of once-a-day 908 plus ritonavir are underway. Data could go to the FDA next year.
In his presentation of tenofovir data during a late breaker session at ICAAC, Joel Gallant of Johns Hopkins University prefaced his talk with a verbal disclosure of his relationships with various pharmaceutical companies. This was a first in my experience; it seemed to cause Dr. Gallant no pain, no one walked out, and the ceiling of the conference center did not collapse. His public disclosure put his cards on the table and allowed the data to be evaluated in the open air. Gallant's breakthrough should become the model for all presenters of clinical trial data.
The FDA announced they have given T-20 priority review status for approval, which means they must say yea-or-nay by March 16, 2003 -- although the agency could act sooner. T-20 sponsor Roche is happy about this, but a persisting problem with drug production has them downplaying expectations about actually being able to deliver the drug to everyone who'll need it. Roche has scheduled a meeting with community members next month to discuss this issue, its expanded access program, and rumors of "golf-ball-sized nodules" at the site of injection. Physicians are returning from Roche training sessions buzzing about the importance of learning proper T-20 preparation and injection techniques. Not a bad idea.
At ICAAC, Kathleen Squires presented 48-week data on Bristol Myers Squibb's low-tox PI hopeful, atazanavir (ATV). BMS 038 compared ATV head-to-head with efavirenz, both once a day, each backed up with standard BID Combivir. Both drugs turned in respectable efficacy results, each bringing similar proportions of the 810 treatment naive participants below 400 copies, although only about half as many went below 50 copies. Resistance to ATV was uncommon, and a tantalizing suggestion was floated that ATV resistance, when it does occur, may possibly increase susceptibility to other PIs.
The great promise of atazanavir is that lipid abnormalities, which have been the bane of other PIs, seem to be absent with this drug. Triglycerides were somewhat elevated in the efavirenz group but actually went down for those on ATV. But this PI has one peculiar trait that will bear watching -- elevated levels of unconjugated bilirubin are associated with ATV and produced 21 cases of jaundice in this trial. If this turns out to be a significant problem with TAZ, unkind consumers could take to calling it "The Yellow Peril."
This large, worldwide study enrolled people into one of the broadest cross-sections of the world epidemic yet studied in a drug company trial and the demographics are notable. Over one third of the participants were women and about two-thirds were non-white. Hopefully, this kind of representation will reflect a trend in Phase III clinical trials to come.