Lonnel Coats, President and Chief Executive Officer of Eisai Inc., stated, "Eisai is committed to collaborating with Arena to address the FDA's requests. Obesity is an epidemic in America, and our goal is to bring lorcaserin to physicians and patients who need additional weight loss options."
ADAM F, Jim Edmund's, Derek Lowe, Ruthanne Russel Williams and other so called journalists with their ulterior motives( very transparent) will BASH this in just matter of time.
Spin this; say this is END of the world for ARNA, let the GAMES begin.
http://finance.yahoo.com/news/FDA-Issues-Complete-Response-prnews-3589036116.html?x=0&.v=1
Excerpt from Arena's news release
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; demonstrate that the apparent increase in aggressiveness of adenocarcinoma in rats administered lorcaserin is reasonably irrelevant to human risk assessment; 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.
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 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.
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Respected Dr. Daniel's comments:
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.
Daniel
UCLA MD
http://messages.finance.yahoo.com/Stocks_%28A_to_Z%29/Stocks_A/threadview?m=tm&bn=1339&tid=170527&mid=170527&tof=5&frt=2
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Thanks to all - This is a HUGE win. Earlier today, I posted somewhere that the best outcome is the FDA asks ARNA for an independent study on the rat issue, and to submit the Bloom-DM data. That allows the FDA to save face by accepting the outsiders study, and resolving the issue of the non-DM study participants being "too healthy." (Total BS for a new chemical entity, incidentally.)
ReplyDeleteIt will take 2 to 3 months to submit the data and about 2 to 3 months for the FDA to respond. I still think approval is a lock. Look for February to April approval.
Folks, the petition and letters worked! Thanks to all who went to the mat on this one.
Michael Murphy
The BORG has restored my faith in political activism and the ability to correct an injustice. The fight continues toward approval.
ReplyDelete@ MM - Thanks for posting here, the fight is not over yet. I am certainly committed to making sure this drug is approved for LOT of GOOD reasons.
ReplyDelete@ Greg N - LONG LIVE BORG!!!
The FDA seems to regard diabetes II as a bigger problem even than obesity, so if the Bloom-DM data shows improved blood glucose levels allowing a retreat from other medications, they will hang onto that. Ironically, then the reduction in weight becomes a bonus, one that will motivate doctors to prescribe for both conditions.
ReplyDeleteI think the Bloom-DM will give them the fuel to grant a conditional approval for diabetes II glucose reduction, with patient monitoring to demonstrate this works and does not introduce heart issues or tumors. When patients of this condition also show weight reduction, the door will open in the future for complete approval.
The FDA has issued the CRL in writing that explains what they need. The final decision still depends on how well Arena meets those issues. We do have to give the FDA credit that they are striving for better ways to deal with obesity and diabetes II and need to be convinced for all our sakes. So, if Arena does the job correctly, I believe they will follow through with an approval.
You also need to consider the fact that ARNA might just screw investors over again. They didn't tell you about the rat-tumor issue until the panel docs came out. What's to say they forget something from the CRL? Think about AMLN screwing up the Bydureon NDA. It happens.
ReplyDelete