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AnnJi Pharmaceutical's Clinical Breakthrough in SBMA Treatment

AnnJi Pharmaceutical Co., Ltd., a Taiwanese biotechnology firm focused on addressing unmet medical needs in various fields including neurology and rare diseases, recently announced promising outcomes from a Phase 1/2a clinical trial of its investigational drug AJ201. This trial specifically targeted adult patients suffering from Spinobulbar Muscular Atrophy (SBMA), a rare neuromuscular disorder that currently lacks FDA-approved treatment options.

Study Overview

The randomized, double-blind, placebo-controlled Phase 1/2a study was conducted across six clinical sites in the United States. Its primary objective was to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of AJ201, with ClinicalTrials.gov Identifier NCT05517603. While the results are preliminary and not sufficient for definitive efficacy assessment, they hint at significant improvements in exploratory endpoints that warrant further development.

Safety and Pharmacokinetics

The safety profile and pharmacokinetics of AJ201 were found to align with previous data from healthy volunteers. Importantly, the drug was generally well tolerated by participants, with no evidence of systemic drug accumulation.

Positive Clinical Signals

The results after 12 weeks of oral treatment are particularly noteworthy. Participants receiving AJ201 demonstrated clinically significant improvements compared to the placebo group in both bodily and muscle functions. For instance, those treated with AJ201 increased their distance in the six-minute walk test (6MWT) by an average of 17.6 meters, along with an increase in scores by 0.8 points on the SBMA Functional Rating Scale (SBMAFRS). Conversely, participants in the placebo group showed slight declines in performance. Additional findings included reductions in serum creatine kinase and myoglobin levels, further indicating a potentially beneficial therapeutic effect. Notably, 11 out of 15 respondents in the AJ201 group improved their 6MWT scores, reinforcing the drug's efficacy.

Moreover, quality of life assessments using the SF36v2 questionnaire revealed a significant positive change in the physical functioning component among AJ201 recipients, whereas the placebo group experienced a decline (p=0.026).

Biomarker Findings and RNA Sequencing

The study also yielded compelling biomarker data. The level of mutant androgen receptor (mAR), a suggested biomarker for SBMA, was measured through muscle biopsies. In 53% of patients treated with AJ201, nuclear mAR levels were reduced by more than 50%, compared to only 17% in the placebo group, hinting at a favorable therapeutic response.

Furthermore, RNA sequencing analysis of muscle biopsies from AJ201-treated patients demonstrated activation of the Nrf2 signaling pathway and modulation of various disease-relevant signaling cascades - changes not observed in the placebo group. These molecular alterations lend mechanistic support to AJ201's therapeutic actions.

Conclusions and Expert Comments

The consistent improvements across functional, biochemical, and molecular markers observed in this trial provides a strong basis for advancing AJ201 as a treatment option for SBMA. Dr. Christopher Grunseich, the study leader and Lasker Clinical Research Fellow, emphasized the study's encouraging results, noting AJ201's clinical benefits manifesting as improvements in functional assessments and favorable shifts in serum biomarkers and RNA sequencing data that support the activation of Nrf2 signaling.

Dr. Wendy Huang, CEO and Chairperson of AnnJi, expressed optimism about the outcomes. She stated, “The positive clinical results observed after a relatively short treatment period with AJ201 are very encouraging. AnnJi is committed to advancing this program into Phase 3 clinical trials, aiming to provide a safe and effective treatment option for patients with SBMA who currently have no approved therapies.”

Understanding SBMA and AJ201

SBMA, also known as Kennedy’s disease, is an inherited X-linked neuromuscular disorder caused by a CAG repeat expansion in the androgen receptor gene (AR). The resulting mutated AR protein contributes to degeneration of muscles and neurons through mechanisms including cellular toxicity, oxidative stress, and neuroinflammation. Affecting about 1 in 40,000 men worldwide, there is currently no FDA-approved treatment available.
AJ201, also referred to as JM17, has shown potential in preclinical SBMA models to mitigate the toxicity associated with the AR mutation and improve motor functions. Mechanistically, it promotes the degradation of the pathogenic mAR protein and induces the expression of anti-oxidative enzymes, proteasome subunits, and heat shock proteins, all of which may slow disease progression.

AnnJi Pharmaceutical Co. Ltd., established in 2014, is dedicated to developing innovative low-molecular therapies for serious and underserved diseases, with a focus on neurology, dermatology, and rare disorders like SBMA. The company aims to translate cutting-edge scientific knowledge into differentiated therapeutic solutions through global collaboration and commercialization efforts. For further information, visit www.ajpharm.com.