RARE Daily

AI Therapeutics Reports Positive Results from Phase 2a Biomarker-driven Trial of AIT-101 in ALS

April 7, 2023

Rare Daily Staff

Rare disease drug developer AI Therapeutics reported positive results from a phase 2a clinical trial of AIT-101 in patients with C9ORF72 amyotrophic lateral sclerosis.

In the study, participants taking AIT-101 demonstrated increased expression of the target engagement biomarker sGPNMB and a 73 percent reduction in the toxic protein aggregate, poly(GP), over 12 weeks.

The study also met its primary endpoints of safety and tolerability, and confirmation of delivery of drug and three active metabolites into the brain.

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s Disease, is a fatal neurological disorder that affects approximately 30,000 patients in the United States, with an average life expectancy of three to five years.

AIT-101 employs a novel approach to clearing toxic protein aggregates that accumulate in the brains of ALS patients and are a hallmark of the disease and has been demonstrated to reduce aggregates in human subjects, to improve the survival of motor neurons in in vitro models of familial and sporadic ALS, and to ameliorate functional deficits in a mutant TDP-43 animal model of ALS.

“AI Therapeutics is acutely aware of the urgent need for new disease-altering agents for underserved patient populations such as ALS. We are encouraged by the results of this initial study of AIT-101, our first-in-class PIKfyve kinase inhibitor,” said Brigette Roberts, CEO of AI Therapeutics. “In particular, we are impressed with the speed and magnitude of reduction of toxic protein aggregates as measured by poly(GP).”

The 24-week study in 15 participants with C9ORF72 ALS consisted of a 12-week, randomized, placebo-controlled portion in which participants were assigned to AIT-101 or placebo in a ratio of 2:1, followed by a 12-week open-label extension and, subsequently, a long-term extension study (ongoing) for study participants. The primary, secondary, and exploratory endpoints included safety, tolerability, cerebrospinal fluid levels of drug and active metabolites, the effect of AIT-101 on biomarkers of target engagement, toxic protein aggregates and neurodegeneration.

“The positive results of this trial are encouraging for further development of AIT-101 in ALS. AIT-101 belongs to a new class of experimental therapeutics that directly target the clearance of toxic protein aggregates in motor neurons, which is a hallmark of ALS. This data may have broad implications for all ALS individuals, not only for C9ORF72 ALS individuals tested in this trial,” said Suma Babu, principal investigator of the trial, physician scientist at the Healey Center for ALS at Massachusetts General Hospital, and assistant professor of Neurology at Harvard Medical School. “This patient-centric, biomarker-driven, phase 2a ALS clinical trial was able to efficiently inform us about the biological efficacy and CNS drug delivery of AIT-101 in C9ORF72 ALS individuals, using a relatively small sample size, short placebo exposure duration and short trial duration overall, while also providing trial completers with the option of long term expanded access to AIT-101.”

Detailed results from the phase 2a trial and the TDP-43 animal model will be submitted for peer-reviewed publication and presentation at a future medical congress.

Photo: Brigette Roberts, CEO of AI Therapeutics




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