BrainStorm Cell Therapeutics Inc (BCLI)

[midastouch017]

BCLI: Relvyrio™ Approval Shows FDA Flexibility for ALS Treatments…

https://finance.yahoo.com/news/bcli-relvyrio-approval-shows-fda-100000480.html

Tue, October 4, 2022 at 1:00 PM

By David Bautz, PhD

NASDAQ:BCLI

On September 29, 2022, Amylyx Pharmaceuticals (NASDAQ:AMLX) announced that the U.S. Food and Drug Administration (FDA) had approved Relvyrio™ (formerly AMX0035) for the treatment of amyotrophic lateral sclerosis (ALS). The approval of Relvyrio comes following a circuitous approval pathway that included the FDA advising Amylyx not to seek approval based on results of the company’s Phase 2 clinical trial, an advisory committee meeting in March 2022 in which advisers narrowly voted against recommending approval of the drug, and then a second advisory committee meeting this month in which committee members voted 7-2 to recommend approval.

One of the largest themes to emerge from the approval process for Relvyrio is the flexibility that the FDA can exert given the overwhelming unmet need for ALS patients. Typically, the FDA requires data from at least one robust Phase 3 clinical trial to approve a drug. Relvyrio was approved based on the results of the Phase 2 CENTAUR trial of 137 ALS patients. Results showed that Relvyrio slowed the rate of decline in patients and a post-hoc analysis showed it increased overall survival when compared to those taking placebo. Importantly, Relvyrio was safe and well tolerated, an important threshold that must be met for the FDA to consider approval. Amylyx is currently conducting the Phase 3 PHOENIX trial in ALS, with results expected in 2024.

The approval of Relvyrio shines a light on the difficult position the FDA is in regarding the approval of therapies with uncertain efficacy for diseases such as ALS where the unmet need for new treatments is so high. Dr. Richard Bedlack, the director of the ALS clinic at Duke University, testified at the September advisory committee meeting that the FDA should err on the side of approving a treatment with questionable efficacy, so long as the treatment is safe and generally well-tolerated, for terminal diseases such as ALS rather than waiting for confirmatory evidence of the drug’s efficacy, such as the case with Relvyrio and a Phase 3 readout expected in 2024. He emphasized what a grave mistake it would be to not approve a drug that turns out to have clear clinical benefit that wasn’t obvious at the time of approval.

BrainStorm Cell Therapeutics (NASDAQ:BCLI) will be filing a biologics license application (BLA) for NurOwn® for the treatment of ALS. The company previously conducted two early stage Phase 1/2 and Phase 2 open label clinical trials in Israel and a Phase 2 trial that was conducted at three clinical sites in the U.S. Results from the Phase 2 U.S. trial were published in the journal ‘Neurology’ in December 2019 and showed that in addition to being well-tolerated, NurOwn achieved multiple secondary efficacy endpoints, including higher response rates at all timepoints over 24 weeks. BrainStorm also tested NurOwn in a Phase 3 clinical trial in ALS for which the company announced topline results in November 2020. While the Phase 3 trial did not reach statistical significance on the primary efficacy endpoint, NurOwn treatment was generally well tolerated and there were no new safety concerns identified. A pre-specified subgroup of those early in the course of the disease (ALSFRS-R > 35) showed that 34.6% of NurOwn-treated patients were responders compared to 15.6% on placebo (P=0.288). However, given the wide range of patients enrolled, including many with advanced disease, these results were not replicated for the study as a whole.

In August 2022, an erratum was published in Muscle & Nerve regarding the publication on the Phase 3 clinical trial of NurOwn® for the treatment of ALS. During a routine quality control check and preparations for the upcoming BLA filing, the company discovered an error in the statistical model utilized by the vendor in the analysis of a key secondary endpoint, which was the average change from baseline to week 28 in ALSFRS-R score for the pre-specified subgroup of patients with ALSFRS-R scores at baseline of ≥35 (an indication of less disease progression). Specifically, the original publication reported results for that endpoint using a model that unintentionally deviated from the pre-specified statistical analysis plan by erroneously incorporating interaction terms between the subgroup and treatment. This was the only outcome in which the statistical model was applied incorrectly, thus no other results changed. Applying the correct statistical model for that outcome resulted in the average difference between NurOwn- and placebo-treated patients going from 2.01 points to 2.09 points, but importantly this difference became statistically significant with a P-value of 0.05. In addition, a statistically significant benefit for NurOwn® compared to placebo for that endpoint is also seen for all subgroups with baseline ALSFRS-R scores of at least 26 through the pre-specified subgroup of 35. While the trial did not reach statistical significance on the primary or secondary endpoints, we believe these corrected analyses support the conclusion that NurOwn has a positive treatment effect for patients with ALS.

Conclusion

When viewed as a whole, we believe the totality of the evidence shows that NurOwn has a positive treatment effect for ALS patients. In addition, NurOwn has been generally well tolerated in all of its clinical trials with no concerning safety issues identified. Assuming the FDA accepts the BLA for NurOwn, which we believe it will, the agency will be in a similar position that it was in with Relvyrio. We believe there is a high likelihood that the agency will again exert its flexibility and offer the ALS community another treatment option by approving NurOwn. As we await additional information on the BLA filing for NurOwn, our valuation remains at $21 per share.


DISCLOSURE: Zacks SCR has received compensation from the issuer directly, from an investment manager, or from an investor relations consulting firm, engaged by the issuer, for providing research coverage for a period of no less than one year. Research articles, as seen here, are part of the service Zacks SCR provides and Zacks SCR receives quarterly payments totaling a maximum fee of up to $40,000 annually for these services provided to or regarding the issuer. Full Disclaimer HERE.