Saturday, October 23, 2010

Lorcaserin and the FDA's Complete Response Letter

Here is a positive assessment of the CRL by Dr. Daniel Lopez:
Here are my initial thoughts in the middle of the night

I think it is positive on several points:

1. Nonclinical issues
- Accounting issue - easily resolved - to make up for the discrepancy between week 96 and final NDA incidence of fibroadenomas and adenocarcinomas
- "demonstrate that the apparent increase in aggressiveness of adenocarcinoma in rats administered lorcaserin is reasonably irrelevant to human risk assessment" - I think that this has already been proven - the key words - apparent and reasonably irrelevant - this can be taken from my letter directly and has been done - Arena just has to provide it.
- "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" should not be a problem

2. Clinical issues
NO NEW STUDIES - will accept BLOOM -DM results. Study already completed, results within a few weeks to 2 months. If the numbers are good then we have a Slam-dunk

Finally "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" Again cancer expert Dr. Gary Williams will be pivotal here. What this sounds like to me is that they have conceded that their conclusions regarding the rat studies were unjustifed and erroneous. They sound like they just want an explanation of why the findings are not relevant to human risk. I believe we have shown that conclusively and they have all the information we have discussed and was sent to them by myself and others.
They have presented a CRL that is in effect a 6 month review or less, maybe 3 months - it will depend how long it will take the pathologists to go over all the slides

And finally a labelling requirement - Schedule IV

From the DEA website:

Schedule IV
• The drug or other substance has a low potential for abuse relative to the drugs or other substances in Schedule III.
• The drug or other substance has a currently accepted medical use in treatment in the United States.
• Abuse of the drug or other substance may lead to limited physical dependence or psychological dependence relative to the drugs or other substances in Schedule III.
• Examples of drugs included in schedule IV are Darvon®, Talwin®, Equanil®, Valium®, and Xanax®.

This is not a problem - it just requires the physician to have a DEA license with Schedule IV prescribing privileges - which almost all physicians have.

However they provided the following path to remove this label: The CRL provided the opportunity to complete preclinical studies that may lead to a different recommendation - again this refers back to the nonclinical issues.

Overall, in my opinion, a very soft and manageable CRL. It's late at night and I am just quickly jotting down a synopsis - after some rest hope to process this more - however I think the jist of it will be the same.


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