Anavex Life Sciences Corp (AVXL)

[Biostockclub]

Good afternoon, Doc

From your post, attributed to the label on Aricept

Quote:
14.1 Mild to Moderate Alzheimer’s Disease
“The effectiveness of ARICEPT as a treatment for mild to moderate Alzheimer’s disease is demonstrated by the results of two randomized, double-blind, placebo-controlled clinical investigations in patients with Alzheimer’s disease...”

Key word: EFFECTIVENESS...IS DEMONSTRATED
Key words missing: APPROVAL WAS GRANTED BASED UPON

Note, there have been many further trials conducted POST-APPROVAL also designed to show its long term effectiveness. This is not out of the ordinary. Just recently, France discontinued reimbursing for this drug based on evidence that it “did more harm than good”. Seems trials never stop on drugs up to and including once they hit the market and have been prescribed for 20 years. Does the label happen to mention that? If not, why not, and wouldn’t that be incomplete information.


Here’s the problem I see with tying the label information to the overall approval process (in your original post, you were speculating upon what would be required for approval of A2-73. So, now I see, it was based upon the package label, which helps to see from whence you speculated on our requirements for approval.)

Burns et al concluded in 1999.

See Watermark link below


Aricept was approved in December 1996

Link:
https://www.centerwatch.com/drug-information/fda-approved-drugs/drug/190/aricept-donepezil-hydrochloride

Burns was NOT part of the APPROVAL process - could not have been as seen by the dates. In fairness, the wording on the label of the package never claimed it was, only that it demonstrated effectiveness. You speculated that a similar trial would be required for the approval (emphasis) of A2-73. Xena said that it might be a ph4 after approval. If this is the case, she was correct.
And, it is also correct that requiring one before approval is not in keeping with a factual account of the clinical approval (emphasis) process, only in demonstrating further effectiveness.

This also from the same link above:

“Clinical Results
Controlled clinical trials in over 900 subjects demonstrated that more than 80% of subjects taking Aricept either improved or exhibited no further demonstration in tests of cognition over the course of the studies. In an assessment of patient function, which includes general function, cognition, behavior and activities of daily living, clinicians rated approximately two times as many subjects on Aricept as improved in comparison to placebo after 24 weeks of treatment.”

IF the Burns trial had been included, that clinical trial participant number would have been much higher than the 900 mentioned above (818 + 473 = 1,291), correct? Therefore, I conclude this drug was NOT APPROVED BASED ON THE BURNS STUDY EVEN THOUGH IT IS CITED ON THE PRODUCT LABEL AS SHOWING “FURTHER EFFECTIVENESS”.



THIS, TOO:
(From cite below)

“Evidence for the beneficial clinical effects of donepezil CONTINUES to grow. Three US double-blind, placebo- controlled clinical trials of donepezil have been reported in the past few years. One was a 12-wk trial in which the highest dose studied was 5 mg?d (Rogers et al., 1996). The other two studies, one of 12 wk (Rogers et al., 1998a) and one of 24 wk (Rogers et al., 1998b) in duration, investigated both 5 and 10 mg?d doses. In addition, another 24-wk, double-blind, placebo-controlled trial of donepezil conducted multinationally has also been com- pleted recently (Burns et al., 1999). The results of all four trials are consistent in their demonstrations of the efficacy, safety and tolerability of donepezil. In addition, pre- liminary data on long-term use of donepezil have also appeared recently (Rogers and Friedhoff, 1998.”

PLEASE NOTE DATES OF THE STUDIES. ANYTHING DATED AFTER 1996 COULD NOT HAVE CONTRIBUTED TO ITS APPROVAL (only continued proof of its effectiveness, which is recently being reversed by France’s regulatory body.)

Fact remains: Aricept was approved based upon Rogers et al, 1996 study I cited of 436 PARTICIPANTS IN THE US. THIS IS NOT SPECULATION NOR MARKETING SOURCE (package label...)



CITE:
https://watermark.silverchair.com/3-Supplement_2-S13.pdf?token=AQECAHi208BE49Ooan9kkhW_Ercy7Dm3ZL_9Cf3qfKAc485ysgAAAkQwggJABgkqhkiG9w0BBwagggIxMIICLQIBADCCAiYGCSqGSIb3DQEHATAeBglghkgBZQMEAS4wEQQM8DXWIyKMz9QMIdSfAgEQgIIB94r6wfLug4_RA7EhqU_6SX4lH9XMBHk23U6ZSIC0eylc5-_LWYANXBKOqb_lh3BRowehvr-RQEkY1QZB1lFuWL0FeM3jVsBjxPtwcCdOzik-0UsqMxV9wLo9HIafCuJP9GwXf7hXqFV34y-0eL8qrU4bDU4qsZMN4gzgU7L-A2gOWNFQtwRPI_LLrztAxL3gKtSKxwLBxL4_MSwjtd7zeRJ6TNkEcL5OyIunf0bgSSSUMuLBLjvND4bAub7U938gvDvVUGFi3Q_F8UfbiIwOqEnqLW3lzSE4y0DEUiCz2dHb4h-sn8FEzB9fLn7Qirfw0WSZOpZRW8uJGXXdls0R4tWj0NwMCK0u5b9PE7gcJqR0PI8VZthbWXsHm15m_NxNW-THgiZEy_VQdEGU2mU1bPaFRiiVJ1SQFJK_0-1rPVw5ianRxNHnOzVuYUvqEIOMXOVLWHJu1hynneOdwApBW_0z_KrZSZp63LTg9j9euo90M0OKG3F2GsfAXSpv5feBCGljbN6Wx6zn15FF_svlsnv9N6bdPxOWmcuoBYGFSYiC6TaDEA5Kkw87cCcgWWqqbjx_GF9YC_h4l__b5TTwO1Zdfb-mZ-ND2lNxZX-b1zjjDSQOYrMjNZSryoRWgXOJgcEyCwp_AkIojGPgKcPxeDQrhe06V7g7



Based upon all of the above, the package label has not altered my understanding of the approval process requirements, nor my impression that A2-73 can be approved in the same manner as Aricept. I stand behind my original post rebutting the fictitious claims of “boogey-trials” needed for approval. Further, I believe that reliance upon packaging for a glimpse into the approval process is a grave mistake when considering the future of a drug company investment, but, I do concede that’s your call.


Best Regards,
Bio