Amylyx Donates CENTAUR Trial Data to PRO-ACT Database for ALS
Data from trial's placebo arm now freely available to researchers
Amylyx Pharmaceuticals has donated data from the CENTAUR Phase 2 trial to the PRO-ACT database — the largest collection ever compiled of de-identified amyotrophic lateral sclerosis (ALS) patient records from clinical trials.
The donated data are from the trial’s placebo arm, and are now freely available to researchers using the PRO-ACT database, which stands for Pooled Resource Open-Access ALS Clinical Trials.
“The only way we are going to find a cure for ALS is if the entire community shares data and builds upon the findings of others — that is how we can continue to move forward and develop innovative therapies to end ALS,” Joshua Cohen and Justin Klee, co-CEOs of Amylyx , said in a company press release.
PRO-ACT was created by the nonprofit Prize4Life in partnership with the NEALS Consortium and the Neurological Clinical Research Institute (NCRI) at Massachusetts General Hospital.
Aiding ALS research
Funded by the ALS Therapy Alliance, Prize4Life, NCRI, and the ALS Association, the platform has received numerous accolades, including, in 2021, the prestigious Healey Center Prize for Innovation in ALS.
The database contains more than 11,600 de-identified records from ALS patients across 28 completed clinical trials that have been both publicly and privately conducted. It is freely available to the scientific community and boasts “demographic, lab, medical and family history, and other data elements,” according to the website.
“The PRO-ACT database enables the type of collaboration necessary to accelerate the search for treatments and, ultimately, cures for ALS,” said Kuldip Dave, PhD, senior vice president of research at the ALS Association.
“By pooling resources and sharing data with researchers around the world, we move closer to creating a world without ALS,” Dave added.
As new data are added, researchers will be able to better understand the disease and develop new models for studying it, organizers say. To date, PRO-ACT has been used as the primary data source for more than 70 research publications, and has been a component of several others. It also has been used as a tool for designing new ALS clinical trials.
“The continued addition of data to the PRO-ACT platform is what makes it a valuable tool to the ALS community,” said ALS patient Avi Kremer, the founder of Prize4Life, and an ALS Association consultant. “Adding data that takes into account newer approaches to ALS treatment allows the community to build on past work and move us closer to a cure.”
Alex Sherman, the director of NCRI’s Center for Innovation and Biomedical Informatics at Mass General, is the current principal investigator of the PRO-ACT platform.
“Letting data sit behind locked doors of a single entity can stifle research by the broader community,” said Sherman, who is also a principal associate in neurology at Harvard Medical School.
“Sharing of data with the broader community allows others to look at things from a different point of view and potentially unlock something that others had missed. We hope companies continue to see the value in sharing data and follow Amylyx in data donations,” Sherman added.
Cytokinetics in August added a decade of findings from three previous ALS trials, involving nearly 600 patients, to the PRO-ACT database.
Clinical trials of AMX0035
Data from the CENTAUR trial, completed in 2019, were used to support Amylyx’s applications to health authorities seeking approval of AMX0035, a fixed-dose combination of tauroursodeoxycholic acid and sodium phenylbutyrate that’s delivered orally by mouth or feeding tube.
The compounds are thought to together protect nerve cells against cellular stress that drives ALS.
The trial, which involved 137 adults who received either AMX0035 or a placebo for six months, met its main goal of significantly outperforming a placebo in its ability to slow functional decline.
Additional data — spanning CENTAUR and its open-label extension study (NCT03488524), during which all participants received AMX0035 — showed that survival was extended by a mean of 6.5 months in patients consistently on the treatment compared with those initially on a placebo.
In March, an advisory committee of the U.S. Food and Drug Administration (FDA) narrowly voted against the existence of sufficient evidence supporting the therapy’s efficacy, noting concerns about CENTAUR’s small number of patients, missing data, and questionable statistical analyses.
That vote was met with criticism from the ALS community, given the unmet need for treatments for the progressive disorder. Patients, caregivers and other advocates cited the therapy’s recent approval and availability in Canada (marketed as Albrioza) as support for a U.S. approval.
In a rare second meeting, meant to review additional analyses of trial data submitted by Amylyx, the advisory committee voted 7-2 in favor of AMX0035. The new analyses suggested ALX0035 extended the median survival time by more than 10 months compared with estimated survival if patients had been on a placebo for the full trial.
The committee’s opinion is not binding, but is expected to be used by the FDA in deciding on AMX0035’s approval; the agency is expected to announce a final decision by September 29.