Long-term use of NurOwn shows survival benefit in ALS: New data
Significantly extended survival seen for patients on cell therapy vs. controls
Long-term treatment with the cell therapy NurOwn (debamestrocel) was found to significantly extend survival in people with amyotrophic lateral sclerosis (ALS) when compared with a matched control group from previous clinical trials, according to new data.
That data, from an expanded access program (EAP), was shared by NurOwn’s developer Brainstorm Cell Therapeutics at the 2024 Annual Northeastern Amyotrophic Lateral Sclerosis Consortium (NEALS) Meeting, held virtually Oct. 21-24.
The poster, “Debamestrocel Long-Term Benefits on Survival and Neurodegeneration in ALS Expanded Access Program, was presented by Bob Dagher, MD, Brainstorm’s executive vice president and chief medical officer.
“We were pleased to provide this important update from the NurOwn EAP with the ALS community at this year’s NEALS meeting,” Dagher said in a company press release. “The encouraging findings suggest that among the 10 ALS participants who received NurOwn during the EAP, there was a long-term survival benefit when compared with the matched control group.”
In fact, according to Brainstorm, “at the last available visit in the EAP, 9/10 participants were alive.”
Small number of patients survived more than 5 months longer than controls
NurOwn treatment first involves collecting mesenchymal stem cells — cells that can self-renew and differentiate into various cell types — from a patient. These cells are engineered in a lab to secrete molecules that promote nerve health, and then injected back into the patient’s spinal canal.
The therapy was previously tested in a Phase 3 clinical trial (NCT03280056), completed in 2020, that enrolled 189 ALS patients with rapidly progressing disease. The participants were randomly assigned to receive three intrathecal, or into-the-spinal canal, injections of NurOwn or a placebo, given eight weeks apart, and were followed for 28 weeks, or about seven months.
While this study had hoped to show NurOwn could slow ALS disease progression, it missed that goal. Some promising results were seen among patients with less advanced disease, but the U.S. Food and Drug Administration considered the available data insufficient to prove the therapy’s effectiveness, ultimately leading the company to drop its application.
After completing the Phase 3 trial, 10 patients — six who had been given the cell therapy and four who had received a placebo — opted to continue into an expanded access program. In that EAP, the participants received a total of six additional injections of the therapy. The program had two 28-week periods in which treatment was given as in the main trial: three injections eight weeks apart, with an additional 12 weeks of follow-up. There was a break in between each period.
Survival findings from these 10 individuals were compared against outcomes from similar patients in PRO-ACT, a database of ALS patients who participated in previous Phase 2 and Phase 3 trials.
These results showed that patients given NurOwn survived for a median of 46.6 months, or nearly two years. This was 5.5 months longer than the survival time seen in the historical controls — a significant difference.
“Promising long-term survival benefits were observed in [NurOwn]-treated participants compared to the PRO-ACT-matched controls,” the researchers concluded, though they noted that these results should be interpreted with care given the small number of patients on which they are based.
Data also suggested that long-term treatment with NurOwn tended to stabilize or decrease levels of neurofilament light chain, known as NfL, which is a well-established marker of nerve damage. Reductions in this nerve damage marker tended to be more dramatic in patients who had been given NurOwn in the original Phase 3 trial, which researchers said supports the idea that long-term treatment with the cell therapy may help lessen the destruction of nerve cells that drives ALS.
“The consistent reductions in NfL observed both during the randomized Phase 3 trial and in the subsequent EAP periods, indicate that patients treated with NurOwn continued to see benefits from the extended treatment. These data align with our understanding of NurOwn’s mechanism of action,” Dagher said.
Brainstorm to test NurOwn in early-stage ALS patients in Phase 3 trial
With guidance from the FDA, Brainstorm is planning a new Phase 3b clinical trial, which the company hopes will prove the therapy works and pave the way toward approval. Brainstorm shared the design for this upcoming trial in a separate poster at NEALS. That poster was titled “An Overview of The Phase 3b Clinical Trial of Debamestrocel in ALS.”
The trial is expected to enroll about 200 people with ALS, ages 18 to 75. To be eligible, patients must have mild to moderate ALS and be no more than two years out from disease onset.
“A key priority for Brainstorm is to confirm NurOwn’s efficacy in the upcoming Phase 3b trial,” Dagher said. “Our goal is to conclusively demonstrate the treatment’s benefits in early-stage ALS patients, hence, we have set the entry criteria to specifically target people living with ALS in the early stage of their disease.”
Over the first six months of the yearlong trial, some participants will receive three injections of NurOwn, also spaced by eight weeks, while others will be given a placebo. Then, in the second half of the trial, all will get three injections of NurOwn.
A key priority for Brainstorm is to confirm NurOwn’s efficacy in the upcoming Phase 3b trial. … Our goal is to conclusively demonstrate the treatment’s benefits in early-stage ALS patients.
Throughout the study, participants will be able to receive approved ALS treatments, including riluzole (sold as Rilutek, Tiglutik, and Exervan), edaravone (sold as Radicava and Radicava ORS), and Qalsody (tofersen).
The study’s main goal is to assess whether NurOwn outperforms the placebo at slowing disease progression, as measured by the ALS Functional Rating Scale-Revised (ALSFRS-R), in the first six months. Secondary measures include a composite assessment of function and survival, as well as evaluations of lung function, muscle strength, quality of life, and caregiver burden.
“We look forward to providing further updates as we advance our trial preparations,” Dagher said.
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