Anavex's Phase 2 Study Is Promising And A Phase 3 Is Warranted

| About: Anavex Life (AVXL)

Summary

Anavex has established the safety of 2-73.

Early efficacy data is promising but must be confirmed.

This study was not meant to address the placebo effect.

This article will contain less scientific esoterica than what I traditionally enjoy writing about. Instead, I will attempt to present a fair analysis of Anavex's (NASDAQ:AVXL) presentations this week at the 2016 Alzheimer's Association International Conference (AAIC) in Toronto.

To be clear, the information presented was not top line data. It was safety data with preliminary results of efficacy that was in no way meant to be interpreted as placebo-controlled or final. Again, please allow me to reiterate: the data that was presented was not meant to convey ultimate efficacy of the drug. It was meant to demonstrate dosing and safety and that is exactly what it did.

However, in traditional fashion, the market reacted as if this was top line data. This is somewhat understandable given the arcane nature of the information - investors crave concrete results and neuropharmacology is incredibly complex - but at the same time the fear mongering I've witnessed is rather disturbing. Indeed, I've observed a number of outlets, including Twitter, Seeking Alpha and The Street publish articles that incite fear through the authors' use of specious assumptions, extreme pessimism and inflammatory rhetoric. To refer to a scientific and medical endeavor as "garbage" when it has been planned, designed and executed by the foremost experts in the field - especially when one possesses an incompatible background to be throwing such stones - is both unprofessional and unbecoming of an author. To indicate that the company stated or implied a cure to Alzheimer's in its endeavors is a rather creative interpretation of unofficial buzz at best and libel at worst.

Yes, it is adaptive design, which is relatively new (1970s). However, adaptive design has significant advantages over more traditional studies - especially in early trials - including ethical, financial and flexibility considerations [A], which even the FDA recognizes [B]. For a small, upstart biotechnology company, an adaptive dose-finding regimen is a viable strategy, as it allows significant data mining (maximum tolerated dose, dose-response curves, etc.) on a rolling and modifiable basis. True, there is known increased Type 1 error with this design strategy but as I said before - the data reported was in no way intended to definitely establish efficacy.

The initial presentation showed a favorable safety profile with predominantly minor adverse events and a high patient retention rate. So far so good.

The real teeth gnashing began after the second poster presentation and subsequent PR, though it seemed like the (ostensibly prewritten) vitriolic articles were circulating before Anavex's PR had even squeaked onto Yahoo. To be fair, the official PR was conservative. It stated the facts about 2-73's early efficacy results, added minimum commentary about its promising nature, and indicated the need for a larger study. That's it. And that's all that was necessary for a small, adaptive phase 2 study. Regardless, the results were immediately attacked, paraded under shockingly false - and possibly intentionally misleading pretense - and dismissed.

Allow me to elaborate briefly on a portion of the efficacy data with a speck of optimism. For all Alzheimer's patients, the measured decline in MMSE scoring is between 1.5 and 4.5 points per year [1,2].

Referring to the second poster presentation, there has been no observed decline in MMSE to this point. That is promising. It's not definitive and proven beyond a reasonable doubt, but it's promising. It's exceptionally promising when one considers that all current methods of Alzheimer's therapy only slow the disease process. The decline, including MMSE measurements, is inexorable [3,4]. Therefore, I am of the opinion that Anavex 2-73 is worthy of further study. It is now a matter of demonstrating drug superiority (or non-inferiority) to the current standard of care (SoC).

In conclusion, Anavex's poster presentations at AAIC revealed preliminary efficacy data but the raison d'etre of this study is safety. Alzheimer's is a remarkably complex and heterogeneous disease process with a ton of variables, which make approaching therapy to it very difficult. To this point, Anavex has taken a very deliberate and cautious approach to addressing Alzheimer's disease via its adaptive phase 2 study design. This methodology benefits the patients, saves money, interdicts futility and establishes a firm foundation for continued study.

Bring on Phase 2/3.

Sources:

A. Chow S-C, Chang M. Adaptive Design Methods in Clinical Trials - a review. Orphanet Journal of Rare Diseases. 2008. 3:11.

B. Guidance for Industry: Adaptive Design Clinical Trials for Drugs and Biologics. 2008.

1. Han L, Cole M, Bellevance F, McCusker J, Primeau F. Tracking
cognitive decline in Alzheimer's disease using the mini-mental state
examination: a meta-analysis. Int Psychogeriatr. 2000 Jun; 12(2):231-47.

2. Zhao Q, Zhou B, Ding D, Teramukai S, Guo Q, et al. Cognitive
Decline in Patients with Alzheimer's Disease and Its Related Factors in a
Memory Clinic Setting, Shanghai, China. PLoS One.

3. Doody RS, Dunn JK, Clark CM, Farlow M, Foster NL, et al. Chronic
donepezil treatment is associated with slowed cognitive decline in
Alzheimer's disease. Dement Geriatr Cogn Disord. 2001
Jul-Aug;12(4):295-300.

4. Rountree SD, Chan W, Pavlik VN, Darby EJ, Siddiqui S, et al.
Persistent treatment with cholinesterase inhibitors and/or memantine slows clinical progression of Alzheimer disease. Alzheimers Res Ther. 2009; 1(2):7.

Disclosure: I am/we are long AVXL.

I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it. I have no business relationship with any company whose stock is mentioned in this article.