Just listened to the CC, and good thing, too. Lots there, and I would recommend it for those interested. Notes:
Timelines for the 2b trial. Six week screening before dosing, to get genotype, phenotype, and resistance info. The post-functional monotherapy review by company and FDA would only take a few weeks, then next cohort starts on go from FDA. Patients who don't manage that 1log10 viral load reduction in 14 days will be dropped. Expansion would be in part to make up for such dropouts; the other reason would be in case dose/response doesn't top out at 600mg. The rationale for discontinuing poor responders is to not dose sub-optimally and alow resistance to build without efficacy. They will report viral load data for each cohort as it becomes available. Expect 400mg cohort data in Q406, 500mg in Q107, and the 600mg data in Q2 07. One analyst thought this was a delay, having expected all data by Q107. I haven't seen prior guidance, so I'm not sure what to make of her impression. The 400mg dose constitutes a somewhat higher dose than patients were exposed to in the 2a and for a longer time. The tablet form being tested has ~60% of the bioavailability of the 200mg oral liquid dose tested in the 2a. So 400mg equals about 240mg of the liquid formula. The 2a tested for 10 days, the 2b for 14. Also there has been synergy with drugs expected to be in the patients in the 2b. Thus one would expect more robust response at this low dose than in the 2a because of more drug exposure per patient and the synergies. They expect the 600mg dose to be at the top of the dose response curve.
Two pivotal trials of 300 to 500 patients expected to beging by YE07, one for naive, one for treated patients. Different design. 24 week data likely endpoint, basis for NDA. Tablet already being designed for single commercial dose. P2 tablets are different in that they are designed for multiple doses. This is the only reformulation expected.
2nd generation compound is an analog of 457, which is now called bevirimat. IND expected later this year. Should be active against strains resistant to bevirimat. 3rd generation compound is from a different chemical series.
Oral fusion inhibitor has nanomolar potency, and acts upstream of Fuzeon target. In clinic next year,with preclinical data to be presented update at upcoming Toronto AIDS confab next month.
Animal tox data in rats (6 months) and marmosets (9 months). Marmosets more sensitive to acute effects. Data to be released within a year.
Drug interaction studies with existing HIV treatments: no antagonism, some synergies observed. Top line data is already public, full data coming at conferences later this year.
They say they are not likely to preview data to potential partners that isn't already public. It would be nice indeed to have a level playing field there for.
Finally, and this is important, they say they have resources to last into '08. Clearly they'll finance or partner before p3, but they should make it to the point of having their p2b data in hand before they run out, which is key.
Cheers, Tuck |
