Replies to post #107055 on Biotech Values

[turtlepower]

Looks like a lot of lipstick was applied to this PR. Even with bloom-dm as the red text in the pr indicates, a potential approval could only be for obese diabetic people. then ARNA has to prove there is no cancer risk and what's it going to take for that. The only positive i can see is that eisai appears to be standing behind the drug which is surprising, to me at least.

[biomaven0]

>>Arena

In my view they should bite the bullet and do a combo trial with phentermine. That's the only way they will be able to demonstrate significant efficacy.

I've always maintained that the marginal efficacy shown to date is the real problem here.

Peter

[iwfal]

ARNA - I thought it might be interesting to look back at the CRL that ARNA originally got and comment on each piece. That said I only have the PRs to look at (none of the posters) - but the PRs do actually have some substantive information:

Saturday October 23, 2010, 2:14 am

SAN DIEGO and WOODCLIFF LAKE, N.J., Oct. 23, 2010 /PRNewswire-FirstCall/ -- Arena Pharmaceuticals, Inc. (Nasdaq:ARNA) and Eisai Inc. announced that the US Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) regarding Arena's New Drug Application (NDA) for lorcaserin. Lorcaserin is intended for weight management, including weight loss and maintenance of weight loss, in patients who are obese (Body Mass Index, or BMI, >/= 30) or patients who are overweight (BMI >/= 27) and have at least one weight-related co-morbid condition.

The FDA has completed its review of the NDA and determined that it cannot approve the application in its present form. In the CRL, the FDA outlined the non-clinical and clinical reasons for their decision.

The non-clinical issues identified by the FDA included diagnostic uncertainty in the classification of mammary masses in female rats, unresolved exposure-response relationship for lorcaserin-emergent mammary adenocarcinoma, and unidentified mode of action and unclear safety margin for lorcaserin-emergent brain astrocytoma.

The CRL included the following requests related to the non-clinical issues: provide a detailed accounting of all slides prepared from female rats that contributed to mammary tumor incidence data in each update to the FDA and to the final study report; in consultation with the FDA, identify an independent pathologist or group of pathologists to re-adjudicate all mammary and lung tissues (neoplastic and nonneoplastic lesions) from all female rats (Comment - this was done via a new advisory group and, in general, the re-analysis lowered the apparent rate of neoplastic mammary tumors. Positive.); demonstrate that the apparent increase in aggressiveness of adenocarcinoma in rats administered lorcaserin is reasonably irrelevant to human risk assessment (Comment - this was done by the same group as above, but in all rat dosages the cancers are clearly more aggressive (i.e. spawn more mets) than placebo. Bad (even very bad since it happens even at the lowest dose)); and provide additional data/information regarding the distribution of lorcaserin to the CNS in animals and human subjects that would clarify or provide a better estimate of astrocytoma exposure margins (Comment - this was done by looking at the spinal fluid vs plasma concentration of rats vs humans and noting that the rats had much more concentration in spinal fluid. Positive).

With respect to the clinical reasons, the FDA stated in the CRL that the weight loss efficacy of lorcaserin in overweight and obese individuals without type 2 diabetes is marginal (Comment - Diabetes trial showed about the same 3% weight loss as the previous 2 trials, and about the same HbA1c reduction as seen in the T2D subpop of the previous trials. Thus still marginal. Bad.) and recommended that Arena submit the final study report of the BLOOM-DM (Behavioral modification and Lorcaserin for Overweight and Obesity Management in Diabetes Mellitus) trial. The FDA also stated in the letter that in the event evidence cannot be provided to alleviate concern regarding clinical relevance of the tumor findings in rats, additional clinical studies may be required to obtain a more robust assessment of lorcaserin's benefit-risk profile.

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.


All in all it doesn't look very good - not really much more information or more positive information than last time. Question: was there some aspect of the VVUS data that really became clearer or better in the last NDA (vs their first NDA)?