Enrollment Complete in Phase 1b/2a Trial for AJ201 in Kennedy's Disease

Avenue Therapeutics, Inc., a pharmaceutical company dedicated to developing and commercializing treatments for neurological diseases, recently announced the completion of patient enrollment in the Phase 1b/2a clinical trial for their drug candidate AJ201. This drug is aimed at treating spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's Disease. Topline data from the trial are expected to be available in the second quarter of 2024.

The 12-week Phase 1b/2a trial is being conducted as a multicenter, randomized, double-blind study involving 25 participants. These patients are randomly assigned to receive either AJ201 at a dosage of 600 mg per day or a placebo. The primary aim of the study is to evaluate the safety and tolerability of AJ201 in individuals diagnosed with SBMA based on clinical and genetic criteria. Due to the slow progression of SBMA, demonstrating clinical efficacy within the 12-week period may be challenging. Therefore, the trial includes secondary endpoints focusing on biomarkers that can indicate the drug’s target engagement, potentially foretelling its clinical success. These biomarkers encompass pharmacodynamic data, such as changes in mutant androgen receptor protein levels in skeletal muscle and variations in muscle and fat composition as observed in MRI scans.

SBMA is a rare genetic neuromuscular disorder that predominately affects men. It results from a trinucleotide CAG repeat expansion in the androgen receptor gene, causing the production of a defective polyglutamine androgen receptor protein. This protein accumulates and leads to muscular atrophy, particularly in the limbs and bulbar regions. The disease manifests in symptoms like impaired chewing, speech difficulties, swallowing problems, and a predisposition to choking or inhaling food, which can cause airway infections. Limb muscle weakness can lead to walking difficulties and fall-related injuries. Although prevalence rates vary, a recent study estimated that SBMA affects approximately 1 in 6,887 males. Currently, there are no approved treatments for SBMA in the U.S. or Europe.

AJ201 is characterized as a first-in-class therapeutic candidate specifically designed to address SBMA through multiple mechanisms. These include promoting the degradation of the abnormal androgen receptor protein and activating the Nrf1 and Nrf2 pathways that help protect cells from oxidative stress. Earlier Phase 1 trials in healthy volunteers indicated that AJ201 has a favorable safety and pharmacokinetic profile. Presently, AJ201 is under investigation in a Phase 1/2a trial across six U.S. clinical sites, aiming to further assess its safety, pharmacokinetics/pharmacodynamics, and clinical response in SBMA patients. The U.S. FDA has also awarded Orphan Drug Designation to AJ201 for SBMA, Huntington’s disease, and spinocerebellar ataxia. Avenue Therapeutics holds the exclusive license for AJ201 in multiple countries, including the United States, Canada, the European Union, Great Britain, and Israel.

Polyglutamine diseases, including SBMA, are a set of neurodegenerative disorders triggered by expanded CAG repeats in specific genes, leading to mutant protein aggregations in tissues. Addressing these diseases involves strategies to enhance the degradation of mutant proteins, stimulate antioxidant and heat shock responses, and increase proteasome expression.

Avenue Therapeutics specializes in neurologic disease treatments and is also developing other therapeutic assets, such as BAER-101 for CNS diseases and IV tramadol for managing acute postoperative pain.