1st Patient Enrolled in Phase 2a Trial Testing AT-1501 in ALS
The trial is enrolling up to 54 adults with ALS across up to 12 U.S. treatment sites. Currently, only the Johns Hopkins University Medical Center has opened enrollment. More contact and recruitment information is available here.
“We anticipate top-line data from this important trial in 2022,” said Steven Perrin, PhD, president and chief scientific officer of Novus, which recently acquired Anelixis Therapeutics, the original developer of the therapy.
AT-1501 works by targeting a protein called CD40 ligand (CD40L), found on the surface of some immune cells. CD40L is known to play a central part in generating the pro-inflammatory responses seen in autoimmune and neurodegenerative diseases. Previous research has found the CD40L pathway overactive in more than half of ALS patients.
Although its exact mechanism of action remains unclear, stopping or delaying immune activation by blocking CD40L may delay the onset or slow the progression of ALS symptoms. This was observed in a preclinical study, in which shutting down the CD40L pathway improved muscle function, slowed disease progression, and improved survival in an ALS mouse model.
“There is strong evidence that the reduction of peripheral neuroinflammation has the capacity to influence disease progression in ALS,” said Merit Cudkowicz, MD, director of the Sean M. Healey & AMG Center for ALS, and chief of neurology at Massachusetts General Hospital, in Boston.
The current trial (NCT04322149) is an open-label, dose-escalating, safety, and biomarker study. It primarily seeks to evaluate the investigational therapy’s safety and tolerability, although it will also measure changes in pro-inflammatory biomarkers and neurofilament light chain — a marker for ALS progression.
Trial participants will receive one of three ascending doses of AT-1501, given intravenously once every other week for 11 weeks. The study is estimated to take 19 weeks for participants.
An earlier Phase 1a/1b single-ascending dose trial in healthy volunteers and ALS patients, completed last year, found AT-1501 safe and well-tolerated at all doses tested.
In addition, the U.S. Food and Drug Administration has granted AT-1501 orphan drug designation for the treatment of ALS. This provides financial incentives for developing rare disease medications, which might not be profitable enough to pursue without government assistance.
“We are in urgent need of new therapies for people living with ALS,” said Michael Rivner, MD, director of the ALS Clinic at Georgia Regents Medical Center, in Augusta. “AT-1501 and the CD40/CD40L pathway represent a highly promising approach to treating this disease.”
Because of its immune system regulatory effects, AT-1501 is being further investigated as a possible treatment for people undergoing organ and cell transplant, as well as people with autoimmune diseases and other neurodegenerative disorders.