Amylyx Pharmaceuticals has made good on its pledge to file for regulatory review of its amyotrophic lateral sclerosis drug. The company said Tuesday that it submitted a new drug application to the FDA based on the results of mid-stage clinical trials, even as the biotech continues with its plans for a larger Phase 3 study.

The experimental Amylyx treatment is already under regulatory review in Canada and a planned submission in Europe remains on track. The FDA submission for the drug, AMX0035, almost didn’t happen. The drug posted positive Phase 2 data, and there is precedent for the agency granting accelerated approval for drugs for diseases with pressing need and few available treatments, such as ALS. But in April, Amylyx said the FDA asked to see more data from another placebo-controlled study. The Cambridge, Massachusetts-based biotech drew up plans for that clinical trial and raised the money to finance it—a $135 million Series C round of funding.

Prospects for an earlier regulatory filing improved over the summer. Amylyx had several talks with the FDA, including a July meeting held specifically to discuss a potential regulatory submission. In September, the company said based on those discussions, it expected to formally seek FDA approval for the drug “in the coming months.”

The Amylyx drug is a pairing of two main pharmaceutical ingredients, taurursodiol and sodium phenylbutyrate. The drug combination is intended to block cellular death pathways in mitochondria, which are the parts of cells that produce energy, as well as in the endoplasmic reticulum, which is a cellular transportation system for proteins.

In a placebo-controlled Phase 2 study enrolling 137 people, the drug met the main goal of showing statistically significant improvement in the slowing of functional decline after six months. The study participants were evaluated under a rating scale used to assess the physical function of ALS patients.

Clinical trial participants had the option to continue in an open-label study that followed them for up to three years. In this extension study, Amylyx reported that those who had started on the Amylyx drug during the placebo-controlled portion of the Phase 2 study showed a 44% lower risk of death compared to those who had started on placebo. Patients who had started on the Amylyx drug also lived longer by an average of about 6.5 months. The study’s results were published last year in the New England Journal of Medicine.

Amylyx has said that the planned Phase 3 test of AMX0035 will enroll about 600 patients in the U.S. and Europe, and will build on the safety and efficacy data produced in Phase 2 testing. The company aims to begin the Phase 3 study later in the current quarter.

Clene Nanomedicine ALS drug fails its Phase 2 test

Clene Nanomedicine is developing nanotherapeutics intended to increase energy production in central nervous system cells and promote the protection and repair of these cells. Lead drug candidate CNM-Au8 failed to achieve the main and secondary goals of a Phase 2 ALS study. However, executives of Salt Lake City-based Clene pointed to results in a subset of patients that they said indicate encouraging signs for the drug, a common refrain among ALS drug developers that have failed in the clinic.

CNM-Au8 is an oral suspension of gold nanocrystals. Clene says that these crystals are able to cross the blood-brain barrier without causing toxic effects associated with synthetic gold compounds or with nanoparticles that are made in other ways. The main goal of the Phase 2 ALS study was to show improvement according to a measure of functioning neurons in a muscle. The secondary goal was a measure of lung function. Despite missing on both of those goals, Clene said a “significant effect” was observed in patients with limb onset ALS after 12 weeks. The company added that this group showed trending improvement at week 36. Clene noted that limb onset ALS accounts for about 70% of ALS patients.

The Clene drug was well tolerated by patients through 36 weeks of oral daily dosing. No serious adverse events were reported. Clene said it expects to present data from the study at the International Symposium on ALS/MND, which is scheduled for December 8-10. In an investor presentation, Clene said that the Phase 2 results support Phase 3 development of its drug.

The Clene drug is already in Phase 3 testing. In 2019, the drug was one of the drugs selected for a pivotal study conducted by the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital. The study is a platform trial, in which multiple treatments are evaluated simultaneously and other treatments are added as they become available. This approach, which has already been used in cancer, is intended to speed up clinical development of ALS therapies. The other two ALS treatments selected for testing in this platform study so far are from UCB and BioHaven Pharmaceutical.

In addition to ALS, Clene is testing its lead drug in chronic optic neuropathy in patients with the stable relapsing form of multiple sclerosis. That program is in Phase 2.

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