Addendum and revision 11 May ’23 — Cassava announced today that dosing inthe Cognition Maintenance Study (CMS) is complete — https://finance.yahoo.com/news/cassava-sciences-completes-patient-dosing-131500155.html. All that remains is to analyze and report the data which will happen in the third quarter of 2023. The link notes that “The CMS dataset remains locked and blinded. After unlocking, the dataset will be analyzed by outside biostatisticians.” This could be a game changer and lead to early FDA approval as the CMS study is double blinded. So it’s worth republishing an earlier (5/22) post on the subject to explain how this might occur.
Cassava’s Cognition Maintenance Study may prove Simufilam works
The FDA will approve less than perfect therapies if there is nothing useful for a serious condition. Consider the following from Proc. Natl. Acad. Sci. vol. 119 e2120512119 ’22
“KRAS is the most frequently mutated oncogene in human cancer, with mutations detected across many lineages, particularly in the pancreas, colon, and lungs. Among the most commonly activating KRAS mutations at codons 12, 13, and 61, G12C occurs in ∼13% of lung and 3% of colorectal carcinomas and at lower frequencies in other tumors.
“In locally advanced or metastatic non–small-cell lung cancer (NSCLC) patients with KRASG12C mutations who have received at least one prior systemic therapy” treatment with sotorasib resulted in the following “objective response in 37.1% of the patients, with a median duration of response was 11.1 months.” This is hardly a cure, but nonetheless “This promising anticancer activity has resulted in accelerated approval from the US Food & Drug Administration”
Which brings me to the current CMS study from Cassava Sciences. I’ll let them speak for themselves. https://finance.yahoo.com/news/cassava-sciences-reports-first-quarter-130000375.html
“Cognition Maintenance Study (CMS) – on-going
In May 2021, we initiated a Cognition Maintenance Study (CMS). This is a double-blind, randomized, placebo-controlled study of simufilam in patients with mild-to-moderate Alzheimer’s disease. Study participants are randomized (1:1) to simufilam or placebo for six months. To enroll in the CMS, patients must have previously completed 12 months or more of open-label treatment with simufilam. The CMS is designed to evaluate simufilam’s effects on cognition and health outcomes in Alzheimer’s patients who continue with drug treatment versus patients who discontinue drug treatment. The target enrollment for the CMS is approximately 100 subjects. Over 75 subjects have been enrolled in the CMS and 35 have completed the study.”
Even though the open label study was not randomized, this one will be.
Only someone who has actually taken care of patients would know the following. People who are getting no benefit from a drug will soon stop taking it. This was particularly true for my experience with Cognex for Alzheimer’s disease.
Which is exactly why the fact that 75 patients who’ve been on Simufilam have decided to continue on in the CMS study. Presumably they feel they are getting some benefit.
There are two possible hookers to this
l. The patients are being paid to enter CMS
2. The original cohort was 200, not all of whom have finished the 1 year. So we don’t know how many could have been in CMS but chose not to.
As I discussed in an earlier post, the most impressive thing (to me at least) was that at 9 months 5/50 had significant improvement in their cognition — here’s a link — https://luysii.wordpress.com/2021/08/25/cassava-sciences-9-month-data-is-probably-better-than-they-realize/.
The CMS study should give us an idea of how they fared at 1 year and at 18 months.
If:
l. gains in cognition were maintained on Simufilam
2. gains in cognition were lost off Simufilam
FDA approval should follow quickly.
Results on the 75 will be available this year. Also available this year will be 1 year results on all 200 entering the open label study.
There are two other double blind studies in progress which will provide more definitive answers, but they are far from full and will take much longer to complete. So stay tuned.
Chemiotics II 