AP-101 holds promise for some with ALS, topline data show
Patients saw clinically meaningful changes after one year
AP-101, AL-S Pharma’s amyotrophic lateral sclerosis (ALS) therapy, was safe and well tolerated and led to clinically meaningful benefits for breathing and survival after one year of treatment.
That’s according to topline data from a now-complete Phase 2a study (NCT05039099) that tested the therapy in 73 adults with sporadic or SOD1-related familial ALS. Trial results also showed the treatment stabilized disease progression and biomarkers of nerve damage.
“We are excited by the topline Phase 2 results of AP-101 for ALS, a devastating degenerative disease for which new treatments are urgently needed,” Michael Salzmann, PhD, CEO of AL-S Pharma, said in a company press release.
ALS is a neurodegenerative disease marked by loss of motor neurons, the specialized nerve cells that facilitate voluntary movement and muscle control. ALS symptoms of progressive muscle weakness affect movement, speaking, swallowing, and breathing.
In up to 20% of familial and 1%-2% of sporadic ALS cases, mutations in the SOD1 gene lead to the formation of an abnormal SOD1 protein that forms toxic clumps inside nerve cells, ultimately causing their death.
Treatment targets protein to preserve neuron function, slow disease progression
Neurimmune and TVM Capital Life Science created AL-S Pharma in 2016 to develop AP-101 using Neurimmune’s Reverse Translational Medicine technology.
AP-101 is an antibody designed to selectively target the abnormal SOD1 protein and prevent its spread in the spinal cord and surrounding fluid. It is administered directly into the bloodstream (intravenous infusion), with the goal of preserving motor neuron function and slowing or stopping ALS progression.
AP-101 holds orphan drug status — a designation meant to speed the clinical development and regulatory review of medicines for rare diseases — in the U.S., European Union, and Switzerland.
Preclinical studies found that AP-101 reduced motor symptoms and prolonged survival in ALS mice. In a Phase 1 study (NCT03981536) with 18 ALS patients, the investigational therapy showed a favorable safety and pharmacological profile at all tested doses.
The Phase 2a study, which enrolled its first participant in 2021, involved 52 adults with sporadic ALS and 21 with SOD1-related familial ALS at sites in the U.S., Canada, Europe, and South Korea. In addition to standard ALS treatment, participants were randomly assigned to receive AP-101 or a placebo for 24 weeks, or about six months. This was followed by a 24-week open-label extension and a safety follow-up period.
The trial’s main goals were to assess AP-101’s safety, tolerability, pharmacokinetics (how it moves into, through, and out of the body), and pharmacodynamics (the therapy’s effects on the body).
“This is the first Phase 2 study to assess an SOD1-targeted therapeutic in both sporadic ALS and in ALS patients with mutations in the SOD1 gene,” said Peter Andersen, PhD, a professor and senior consultant neurologist at Umea University in Sweden and principal investigator for the clinical trial. “The study allowed us to rigorously assess patient safety, pharmacokinetics, and early signals of biological activity.”
After one year of treatment, the trial met its primary outcome related to safety and tolerability, AL-S Pharma said, and results also showed clinically meaningful changes in exploratory efficacy measures of survival and noninvasive ventilatory support, as well as the stabilization of disease stage and neurofilament levels, a biomarker of nerve damage. The company didn’t elaborate.
“The completion of the trial marks an important step in evaluating the therapeutic potential of AP-101 for broad use in patients with ALS,” Andersen said. “The results support the hypothesis that misfolded SOD1 protein plays a more general role in ALS.”
The company said it will share the findings with regulatory authorities and present them at two upcoming ALS conferences: the Northeast Amyotrophic Lateral Sclerosis Consortium (NEALS) annual meeting in October and the 36th International Symposium on ALS/MND in December.
“We are grateful to the participants, their families and the international network of ALS experts who made this trial possible, and we look forward to sharing results from the study at the International Symposium on ALS/MND,” Salzmann said.
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