BrainStorm Cell Therapeutics Inc (BCLI)

[Fmello]

From the Facebook No More Excuses ALS Watchdog Group:

“There are both biological and clinical signals of a treatment effect — as a community, we must review these carefully,” said Merit Cudkowicz, MD, the study’s first author and one of the trial’s principal investigators.

"A significantly greater proportion of ALS patients with less severe disease showed slower ALS progression with ... #NurOwn."

For a drug to be approved by the FDA, the manufacturer must show three things:

1) Clinically meaningful benefits
2) Statistical significance of 0.05 p-value
3) The drug is safe

This study published in Muscle & Nerve shows it can meet all three requirements.

TRIAL'S PRIMARY ENDPOINT
To prove clinical meaningfulness, the trial's primary endpoint test was whether patients had a slower rate of decline by at least 1.25-points on the ALSFRS-R scale. This is clinical proof of a "clinically meaningful" effect.
In the topline data released from the pre-specified subgroup, "twice as many" people on NurOwn vs placebo, (34.6% vs. 15.6%), showed slower disease progression but the sample size of those above 35 was not large enough to reach statistical significance.
In the peer-reviewed study, Brainstorm looked at only those people with an ALSFRS-R score of 26+. This was 77% of the people in the Phase 3 trial.

In this group, slower disease progression was achieved by 34.7% of patients receiving NurOwn and 20.5% of those on a placebo -- and the p-value was 0.056 - minute fractions away from meeting statistical significance. But as the article properly note: statistical significance was met for people at 27+.

SECONDARY ENDPOINT
The data published in Muscle & Nerve shows NurOwn also met its secondary endpoint when analyzing the people with ALSFRS-R of 26+. This is clinical proof of a "clinically meaningful" effect.

The secondary endpoint measured the Change from Baseline ALSFRS-R score. The difference of those on NurOwn vs placebo was TWO POINTS -- which is clinically meaningful -- and with the larger sample size, it was enough to meet statistical significance.

The higher your baseline score, the larger the difference. For example, people at 34+ had an average of 2.74 difference from placebo.

BIOMARKERS PROVED CLINICAL MEANINGFUL EFFECT
The NurOwn trial had the most significant biomarker data in any ALS trial. As noted by ALSNewsToday, the CSF showed significant changes in biomarkers of neuroflammation, neurodegeneration & neuroprotection. This is biological proof of a "clinically meaningful" effect.

Importantly 100% of people on NurOwn had these changes and 0% of people on placebo had these changes. This corroborates the patients reported outcomes that people have been speaking about since 2015.

“Understanding how to use biomarkers to tailor treatments, like NurOwn, is an essential new direction in ALS therapy development,” added Merit Cudkowicz, who is also the director of the Healey Center for ALS and chief of neurology at Mass General. She was the leading PI in the trial.

SAFETY
There are no safety concerns with NurOwn.

Brainstorm - File the BLA for Accelerated Approval
As outlined in this article, because we now have clinical proof & biological proof of a clinical meaningful effect, NurOwn must be approved.

We believe the evidence supports Brainstorm filing the BLA seeking approval under the Accelerated Approval pathway. This allows the FDA to use the biomarker data to supplement the data from the trial to support putting NurOwn out onto the market with what is called a Phase 4 approval.

The would allow people to access NurOwn and insurance would cover it just like a chemo treatment for cancer. The Phase 4 approval simply would require Brainstorm to continue to collect data from the people receiving NurOwn so we could learn more about disease progression when more doses than 3 are received.

We also believe the EAP data will further support the "clinically meaningfulness" test and that all the "patient reported outcomes" corroborate that NurOwn has a clinically meaningful effect.

Every person with ALS knows that 2-3 points difference in decline over a 16 week period is MASSIVE. That is the difference between walking or using a wheelchair... the difference between feeding yourself or having to be fed.

A Phase 4 study would allow us to see changes over the years and with many more consecutive doses.