Several years ago we discussed potential scenarios related to the outcome of Cassava’s Phase 3 program. To remind our readers, concerns were repeatedly expressed over the quality of studies conducted by Cassava Sciences with its lead drug simufilam (here here).  

If these studies were to fail, we would have a telling example about the negative consequences of deviating from good research practices. However, a more difficult outcome scenario would be if these studies succeeded (despite the data quality issues). Then all our wisdom about research rigor would be worth nothing since the winner is always right. 

As recently announced, Cassava studies failed and we have now rather ambivalent feelings.  

On the one hand, we have to admit that it almost feels like a relief because drug development should not be a roulette. 

On the other hand, this is bad news for the patients whose expectations were betrayed by whoever made the decision to fund Cassava’s program (and thereby depriving better deserved projects from getting funded). 

Cassava may not be a unique case. Another example is CervoMed (former EIP Pharma) that we have been following for several years and that recently disclosed negative results from yet another clinical RCT. 

The key publication describing preclinical profile of their lead asset was flagged on PubPeer and also caught our attention for several reasons such as, e.g.: 

• Data presented in Figure 2D do not match those provided in the source data file. There were apparently some data excluded from analysis without being mentioned (and, interestingly enough, subjecting the provided dataset to GraphPad Prism replicates ANOVA results but not the P value); 

• Regarding the sample size and number of animals used for each study, the Reporting Summary states that ‘no statistical methods were used to predetermine sample sizes, but our sample sizes are choices according to those reported in previous publications’. 

All of the above might be acceptable for exploratory research but we are convinced that clinical trials should be initiated based on much more rigorous evidence (hopefully, readers of this newsletter share our view).  

Did CervoMed have better quality data that were left unpublished? We do not know because, for IP or other business reasons, companies often delay or avoid publication of data.  

This lack of transparency reveals another category of stakeholders getting disappointed by the news from Cassava, CervoMed and others – those who buy shares of these companies. As previously discussed, a large proportion of biotech companies are publicly traded without having any asset beyond clinical proof-of-concept. 

What makes people invest into stocks of such companies? Prior achievements of the management team? Backing by key opinion leaders? Or skillful presentation of exploratory data as decision-enabling?  

Or, perhaps, is it the fear of missing an opportunity? A colleague recently wrote to us explaining that, “… in a financial sense, it would be more “risky” to short-sell small cap biotech stocks than to own small cap biotech stocks. That is because if you own a stock, you can lose no more than 100% of your investment. If you are short a stock, and it goes up from 40 cents a share to $4 a share, you have lost 1000%.” 

Indeed, what if one does take concerns about research rigor serious but Cassavas and CervoMeds still succeed?