Patient Enrolled in Phase 2 Trial of Experimental Therapy AP-101

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by Marta Figueiredo PhD |

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AP-101 | ALS News Today | AL-S Pharma AG | illustration of clinical trial meds

A Phase 2 clinical trial evaluating AL-S Pharma AG’s experimental therapy AP-101 in people with amyotrophic lateral sclerosis (ALS) has enrolled its first patient.

The study (NCT05039099) already is recruiting up to 63 adults with sporadic and SOD1-related familial ALS at one of its Canadian sites. Other sites in Canada, as well as in the U.S. and Sweden, are planned to start enrolling; more information is available here. Top-line data are expected by mid-2023.

The trial’s start follows evidence of AP-101’s favorable safety and pharmacological profiles, at all tested doses, in a Phase 1 study (NCT03981536) also involving ALS patients.

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“We are excited to initiate Phase 2 clinical development of AP-101 and hope to provide therapeutic benefit to patients suffering from ALS,” Michael Salzmann, AL-S Pharma’s CEO, said in a press release.

“AP-101 is a human antibody that selectively binds to misfolded and aggregated forms of SOD1,” and “our goal is to neutralize and remove these abnormal proteins,” said Salzmaan, who also is the chief operating officer of Neurimmune, which, together with TVM Capital Life Science, founded ALS-S Pharma to develop AP-101.

Mutations in the SOD1 gene, which provides the instructions to make the SOD1 enzyme, are estimated to cause up to 20% of cases of familial ALS and 1–2% of those of sporadic ALS. These mutations result in the formation of abnormal SOD1 protein that forms toxic clumps inside nerve cells, ultimately leading to their death.

By selectively targeting the abnormal SOD1 protein, AP-101 is expected to slow or halt ALS progression. In a mouse model of the disease, the therapy was shown to reduce motor symptoms and prolong survival.

AP-101, administered directly into the bloodstream, received orphan drug designation in the U.S., European Union, and Switzerland for the treatment of ALS. The designation is meant to speed the therapy’s clinical development and regulatory review.

“In general, AP-101 has demonstrated to be safe and well-tolerated in the ongoing Phase 1 single ascending dose study in familial and sporadic ALS patients,” said Angela Genge, MD, director of the clinical research unit at the Montreal Neurological Institute, in Canada, and the global principal investigator.

“Evaluating multiple doses of AP-101 in patients over a time of up to 48 weeks is now an important next step in our efforts to understand the potential of this investigational drug candidate for the treatment ALS,” Genge added.

The Phase 2 trial will evaluate AP-101’s safety, tolerability, pharmacokinetics, and pharmacodynamics against a placebo in adults with familial ALS caused by SOD1 mutations or with sporadic forms of ALS. Pharmacokinetics refers to the therapy’s movement into, through, and out of the body;  pharmacodynamics denotes the therapy’s effects on the body.

Participants will receive either multiple ascending doses of AP-101 or a placebo for up to 48 weeks (nearly one year). Researchers also will assess changes in the levels of specific neurofilaments, a marker of nerve cell damage.