AnnJi Pharmaceutical has announced encouraging results from its Phase 1/2a clinical trial of AJ201, a novel oral therapy for Spinal and Bulbar Muscular Atrophy (SBMA), also known as Kennedy's disease. The randomized, double-blind, placebo-controlled study, conducted across six U.S. clinical sites, evaluated the drug in adult patients with this rare neuromuscular disorder.
The trial (NCT05517603) primarily assessed safety, tolerability, and pharmacokinetics, but also included exploratory efficacy endpoints that revealed promising therapeutic potential for this currently untreatable condition.
Safety Profile and Pharmacokinetics
AJ201 demonstrated a favorable safety profile in SBMA patients, consistent with previous data from healthy volunteers. The drug was generally well-tolerated with no evidence of systemic accumulation during the treatment period, an important consideration for chronic administration.
Functional Improvements and Clinical Signals
Despite the relatively short 12-week treatment duration, patients receiving AJ201 showed clinically meaningful improvements compared to those on placebo. Key findings included:
- A 17.6-meter gain in the 6-Minute Walk Test (6MWT) for AJ201 recipients, while the placebo group showed slight declines
- A 0.8-point increase in the SBMA Functional Rating Scale (SBMAFRS) among treated patients
- Reductions in serum creatine kinase and myoglobin levels, suggesting a positive effect on muscle health
- Significant improvement in the physical function component of the SF36v2 quality-of-life questionnaire (p=0.026)
The response rates strongly favored AJ201, with 11 of 15 patients showing improvements in the 6MWT, 6 of 7 in SBMAFRS, and nearly all treated patients showing positive changes in muscle biomarkers.
Molecular Evidence Supporting Mechanism of Action
The trial included sophisticated biomarker analyses that provided insights into AJ201's mechanism of action. Muscle biopsies revealed that nuclear mutant androgen receptor (mAR) levels—a proposed biomarker for SBMA—were reduced by more than 50% in 53% of AJ201-treated patients, compared to only 17% of those receiving placebo.
RNA sequencing of muscle tissue from treated patients demonstrated activation of the Nrf2 pathway and modulation of several disease-relevant signaling cascades. These molecular changes were not observed in the placebo group, providing further evidence for AJ201's therapeutic activity.
Expert Perspectives
Dr. Christopher Grunseich, Principal Investigator and Head of the Inherited Neuromuscular Diseases Unit at the National Institute of Neurological Disorders and Stroke (NINDS), expressed optimism about the findings.
"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 Dr. Grunseich.
Wendy Huang, Ph.D., Chief Executive Officer and Chairperson of the Board at AnnJi, highlighted the significance of seeing positive outcomes in a relatively short timeframe for a slowly progressing disorder.
"SBMA is a slowly progressing neuromuscular disorder, and I am greatly encouraged by the positive clinical outcomes observed after a relatively short course of AJ201 treatment," said Dr. Huang. "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."
Understanding SBMA and AJ201's Approach
SBMA is a rare X-linked inherited neuromuscular disorder caused by CAG repeat expansion in the androgen receptor (AR) gene. The resulting mutant AR protein contributes to muscle and neuron degeneration through mechanisms involving cellular toxicity, oxidative stress, and neuroinflammation. The condition affects approximately 1 in 40,000 males globally.
AJ201, also known as JM17, represents a novel therapeutic approach for SBMA. The investigational compound has demonstrated potential in reducing mutant AR toxicity and improving motor function in preclinical models. At the molecular level, it promotes degradation of pathogenic mAR protein and induces expression of antioxidant enzymes, proteasome subunits, and heat shock proteins—mechanisms that may collectively slow disease progression.
Path Forward
Based on these encouraging Phase 1/2a results, AnnJi Pharmaceutical plans to advance AJ201 into Phase 3 clinical trials. The company, founded in 2014 and based in Taiwan, focuses on developing first-in-class small molecule therapies for serious and underserved diseases, with a pipeline spanning neurology, dermatology, and rare disorders.
For SBMA patients and their families, the development of AJ201 represents a potential breakthrough in a field where treatment options have been nonexistent. The progression to Phase 3 trials marks a significant step toward addressing this unmet medical need.
