Biogen trial of ALS drug fails main goal, but company says data are encouraging

By Deena Beasley

Oct 17 (Reuters) - A late-stage trial of Biogen Inc's experimental treatment for an inherited form of amyotrophic lateral sclerosis (ALS) failed to reach its main goal, but secondary measures and biomarkers showed favorable trends, the company said on Sunday.

Biogen will engage with regulators and other stakeholders "to understand the meaningfulness of this data and potential paths forward," Toby Ferguson, head of the neuromuscular development unit at Biogen, told Reuters. The company is treating trial patients in a follow-on study and recently launched a Phase 3 trial of the drug, tofersen, in patients who are not yet experiencing ALS symptoms.

Tofersen, administered directly into the spinal canal each month, is designed to suppress the production of SOD1, a protein that can accumulate to toxic levels in ALS patients with mutations in a specific gene. Around 2% of ALS cases are believed to be caused by the genetic mutation.

After 28 weeks of treatment, the 108-patient trial showed a 1.2-point difference on a scale evaluating functional status for patients with fast-progressing ALS who were given tofersen compared to placebo patients, which was not statistically significant. In the group of patients with slower-progressing disease, the difference was 1.4 points.

An improvement of at least 2 points would be clinically meaningful, Guggenheim Partners said in a recent research report.

Biogen also detailed results from secondary trial endpoints, including breathing ability and muscular strength, indicating that patients treated with tofersen fared better than placebo patients, and that placebo patients switched to the drug in the extension phase of the study experienced similar gains.

"Despite the fact that there was no statistically significant difference in the primary endpoint, there is a clinical signal here," said Dr. Timothy Miller, the study's lead investigator and ALS Center Director at Washington University School of Medicine, St. Louis. He presented the tofersen data at the annual meeting of the American Neurological Association.

The trial also showed that patients given tofersen had lower levels of SOD1 protein compared to placebo patients, as well as lower levels of plasma neurofilament light chain, a potential marker of nerve cell degeneration.

"That suggests that there is an effect on clinical function of the person," Dr. Miller said.

Most side effects in trial patients were mild to moderate, including headache and back pain, but two patients experienced spinal cord inflammation, and 5.6% of tofersen patients dropped out of the study.

Globally, around 168,000 people have ALS, a fatal neurological disorder also known as Lou Gehrig’s disease. Around 10% of cases are linked to genetic mutations, including SOD1.

Biogen, which licensed tofersen from Ionis Pharmaceuticals Inc, now plans to open early access to the drug to all patients with SOD1-associated ALS. In countries allowing such programs, patients can access a medicine free of charge before it is licensed commercially.

Shares of Biogen have fallen by about a third after hitting $414 in early June on the U.S. Food and Drug Administration's controversial approval of Alzheimer's drug Aduhelm. The agency's decision to approve the drug based on evidence that it removes protein plaques associated with the brain-wasting disease, rather than proof that it improves cognition, led to a backlash that has curtailed use of the medication while Medicare, the U.S. health plan for seniors, works to develop payment terms. (Reporting By Deena Beasley; Editing by Andrea Ricci)