Treatment with AJ201 shows positive signs in SBMA clinical trial
Therapy for type of SMA demonstrated good safety profile, hints of efficacy
Treatment with AJ201 was well tolerated and showed signs of improving physical activity in a clinical trial involving people with spinal and bulbar muscular atrophy (SBMA), according to new data announced by developer Annji Pharmaceutical.
“I am greatly encouraged by the positive clinical outcomes observed after a relatively short course of AJ201 treatment,” Wendy Huang, PhD, CEO and chairperson of the board at Annji, said in a company press release detailing the findings of the therapy’s first-in-human trial.
“Annji is committed to advancing the program into Phase 3 clinical trials, with the aim of delivering a safe, effective, and much-needed therapeutic option for patients living with SBMA — a disease that currently lacks any FDA-approved treatments,” Huang said.
SBMA, also known as Kennedy’s disease, is a rare type of SMA caused by mutations in the gene that provides instructions for making a protein called androgen receptor, or AR. In SBMA, the AR protein is abnormally large and has an altered structure, causing dysfunction and death of nerve cells. This ultimately drives disease symptoms like muscle weakness close to the trunk and in the throat.
Experimental SBMA treatment ‘generally well tolerated’
AJ201 is an investigational oral medication that, according to Annji, has been shown in preclinical models to help clear out toxic clumps of AR protein, ease muscle wasting, and activate the production of antioxidant enzymes. Among other cellular effects, AJ201 activates the Nrf2 molecular pathway, a key cellular defense mechanism against oxidative damage.
Annji sponsored a Phase 1b/2a clinical trial (NCT05517603) to test AJ201 in people with SBMA. The study enrolled 25 adults, who were randomly assigned to take AJ201 or a placebo for 12 weeks (about three months).
The study’s main goal was to assess the safety of AJ201. According to Annji, the experimental treatment was “generally well tolerated,” with a safety profile comparable to what was seen in an earlier Phase 1 study (NCT04392830) that tested AJ201 in healthy volunteers. The company didn’t give further details.
The Phase 1b/2a trial was not designed to draw statistically rigorous conclusions about efficacy, the company noted. Nonetheless, some promising trends were seen, per Annji.
Patients saw improvement on 6-minute walk test
On the 6-minute walk test (6MWT), which measures how far someone can walk for that duration of time, patients given AJ201 improved by an average of 17.6 meters (about 58 feet). Patients given AJ201 also showed improvements on a standard physical function measure called the SBMA Functional Rating Scale (SBMAFRS), by slightly less than a point on average. By contrast, average scores on the 6MWT and SBMAFRS tended to worsen over time for patients given the placebo.
Patient-reported assessments of physical function also improved significantly among participants given AJ201, but worsened for those given the placebo. Additionally, participants given AJ201 tended to show decreases in serum (blood) levels of creatine kinase and myoglobin, which are biomarkers of muscle damage.
Muscle biopsies showed that slightly more than half of patients given AJ201 had a reduction greater than 50% in the amount of mutant AR protein clumped up in the nucleus of muscle cells. In comparison, 17% of patients on the placebo showed such reductions. Analyses of genetic activity in muscle cells suggested that AJ201 led to activation of the Nrf2 pathway, as designed.
“The study results are highly encouraging. AJ201 has shown evidence of clinical benefit, demonstrated through improvements in functional assessments, positive shifts in serum biomarkers, and RNA sequencing data supporting activation of the Nrf2 pathway. Together, these findings reinforce the therapeutic potential of AJ201,” said Christopher Grunseich, MD, principal investigator of the study at the National Institute of Neurological Disorders and Stroke, which is part of the National Institutes of Health.
Annji is developing AJ201 in much of the world. Avenue Therapeutics has acquired rights to develop AJ201 in the U.S., the European Union, and select other regions.
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