Bristol-Myers-Squibb presented the first efficacy data on its once-a-day protease inhibitor BMS 232,632 at the Seventh Retroviruses Conference in San Francisco today, which shows that the drug is comparable to other PIs and without serious adverse effects.
The company tested the drug in 89 patients who were randomised to receive one of three doses or nelfinavir three times a day for the first two weeks, after which once daily ddI and twice daily d4T were added.
After 16 weeks viral load had fallen by approximately 2.5 log, from a mean of 63,000 copies to a mean of 200 copies in the BMS 232,632 recipients, and this was comparable to the impact of nelfinavir. Looked at another way, 60% of patients still on treatment had viral load below 400 copies at 16 weeks, and 40% had viral load below 50 copies at 16 weeks.
The main side effect was diarrhoea, reported in approximately 30% of patients taking the new PI, compared with 60% of those taking nelfinavir. The diarrhoea was also less severe, and no other significant events were reported except one case of dose related hyperbilirubinemia.
Dr. Ian Stanne of the Johannesburg Hospital in South Africa, where the drug is being tested, also highlighted the safety margin of the once-daily drug. Some doctors have expressed concern at this conference over the move to once-daily dosing now being investigated by some companies, because they fear that people who miss a single daily dose will spend longer with sub-optimal drug levels than people who miss one of two daily doses. A single dose of BMS-232,632 maintains plasma levels above the minimum necessary for viral suppression (the IC50) for over 28 hours on an empty stomach, and pharmacokinetic tests are currently looking at the extent to which food and serial dosing will extend the half-life of the drug. Synergistic pharmacokinetic interactions cannot be ruled out either.
Trials of BMS 232,632 will begin later this year in the UK.
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Reference
Stanne I et al. Safety and antiviral efficacy of a novel once-a-day HIV-1 protease inhibitor, BMS-232,632: preliminary results from a phase II clinical trial. Abstract 672, Seventh Conference on Retroviruses, San Francisco, 2000.