Replies to post #140191 on Biotech Values

[biomaven0]

Question: was there some aspect of the VVUS data that really became clearer or better in the last NDA (vs their first NDA)?

The FORTRESS study of birth defects with topiramate was new. That enabled the FDA to feel comfortable with an upper bound on cleft palates and other defects. There was also some longer term data showing efficacy was mostly maintained for up to two years and some updated safety data.

Peter

[iwfal]

ARNA -

In addition it should be noted that in the diabetes trial that matured after the CRL the valvular issues showed up looking poor. This is in contrast to the previous trials where they looked right on the edge of meeting the govt's requirement to be acceptable - so the bad results in the diabetes trial kicks them over the edge unless the FDA has already accepted the previous trials as proof positive of acceptability on this issue.

It turns out that ARNA is putting out a fair amount of material - in 8k's. And regarding the above issue it is in fact true that the BLOOM-DM trial put them over the ARNA described limits that the FDA gave to them for valvulopathy. See the below quotes from the linked 8k :

The trial designs entailed combining data from all three trials to provide a sufficient number of patients to rule out a 50% or greater increase in risk of FDA-defined valvulopathy at Week 52 in patients taking lorcaserin as compared to patients taking placebo, ...

Point estimates for relative risk of FDA-defined valvulopathy associated with lorcaserin treatment were 1.03 (completers, 95% confidence interval: 0.68, 1.57) and 1.16 (MITT-LOCF, 95% confidence interval: 0.81, 1.67) at Week 52. Using additional statistical analyses that included all available echocardiograms over up to two years of exposure to lorcaserin, the risk or hazard ratios ranged from 1.08 to 1.09, with the upper bound of the 95% confidence intervals less than 1.5.

MITT-LOCF is the analysis used everywhere else in ARNA's submissions and was not objected to in the last AC - but as you can see from the italicized text ARNA now fails the FDA criteria for ruling out valvulopathy.

On a wider note - it appears that ARNA may have gotten pretty good at hiding the negative data in text most people won't understand in documents most people don't read - while still protecting themselves from lawsuits.