OrphAI’s AIT-101 granted orphan drug status in Europe for ALS
In small US clinical trial, therapy met main goals of safety, efficacy
OrphAI Therapeutics’ experimental therapy AIT-101 has been awarded orphan drug status in the European Union for amyotrophic lateral sclerosis (ALS), following a similar designation granted in the U.S. last year.
In Europe, orphan drug status is given to medicines designed to treat life-threatening or chronically debilitating conditions affecting fewer than five in every 10,000 people. It provides companies with a range of benefits, including assistance with trial protocols, reduced regulatory fees, and 10 years of market exclusivity if the treatment is ultimately approved.
Similar benefits are awarded in the U.S., where the therapy received such a designation last June from the U.S. Food and Drug Administration (FDA), though the market exclusivity period is seven years.
“OrphAI Therapeutics now has orphan designation for AIT-101 both in the US and the EU for the treatment of ALS, an important step toward bringing the drug to patients suffering from this neurodegenerative disorder,” Brigette Roberts, MD, OrphAI’s CEO and director, said in a company press release.
“We look forward to moving AIT-101 into the next stage of clinical development,” Roberts added.
AIT-101 awarded orphan drug status in US last year
The molecular mechanisms that cause ALS are not fully understood, but most cases of the progressive disease are marked by the accumulation of toxic TDP-43 clumps in motor neurons — the nerve cells that control voluntary movements and are lost in ALS. These clumps trigger a number of stress responses in cells that ultimately contribute to motor neuron dysfunction and death.
AIT-101, also called LAM-002A or apilimod, is an experimental oral therapy that’s designed to activate cells’ waste disposal systems. Included in those systems are lysosomes — membrane-bound organelles containing enzymes that break down cellular waste — and autophagy, a cellular process that involves the degradation and recycling of larger cell components that are no longer needed.
By activating these two processes, AIT-101 is expected to help clear the misfolded proteins and toxic protein clumps that contribute to disease progression. The therapy works by inhibiting, or blocking, a protein called PIKfyve.
In preclinical studies, AIT-101 was shown to clear toxic protein clumps and improve the survival of motor neurons derived from ALS patients. Moreover, the therapy was effective at improving functional deficits in a mouse model of ALS.
Its use “in relevant animal models has been shown to reverse the pathological [disease-causing] and functional consequences of … toxic aggregates,” or clumps, OrphAI notes on its webpage.
AIT-101 was investigated in a recently completed Phase 2a clinical trial (NCT05163886) involving 15 adults with ALS caused by mutations in the C9orf72 gene. Such mutations are the most common genetic cause of ALS; the C9orf72 gene carries instructions for a protein of the same name, necessary for the production of lysosomes.
In the trial, participants were randomly assigned to take oral capsules of AIT-101 or a placebo, twice daily, for 12 weeks, or about three months. Then, for the next 12 weeks, all participants received AIT-101.
The trial met its main goal of showing that AIT-101 was generally safe and well tolerated, and was able to reach the patients’ brains. Moreover, the therapy significantly reduced the levels of toxic protein clumps derived from the mutated C9orf72 gene by 73%, and increased the levels of another marker suggesting the therapy was affecting the PIKfyve protein as expected.
According to the company, AIT-101 is “the most clinically advanced PIKfyve inhibitor in development.”
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