Enrollment Complete in AJ201 Trial for Kennedy's Disease

Avenue Therapeutics Inc., a specialty pharmaceutical company dedicated to developing and commercializing treatments for neurologic diseases, has announced the full enrollment of patients in its Phase 1b/2a clinical trial of AJ201. This trial aims to treat spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's Disease. AJ201 is the lead drug candidate for SBMA in Avenue's development pipeline, with topline results expected in the second quarter of 2024.

The trial is a 12-week, multicenter, randomized, double-blind study that includes 25 patients who have either been assigned to receive AJ201 (600 mg/day) or a placebo. The primary goal of this study is to evaluate the safety and tolerability of AJ201 in individuals with clinically and genetically confirmed SBMA. Given the slow progression of SBMA, it is challenging to demonstrate clinical efficacy in such a short period. However, secondary endpoints focusing on various biomarkers have been established to support proof of target engagement, which could indicate potential clinical success. These biomarkers include changes in mutant androgen receptor protein levels in skeletal muscle and alterations in fat and muscle composition as observed through MRI scans.

Spinal and bulbar muscular atrophy is a rare genetic neuromuscular disorder primarily affecting men. This X-linked condition arises from an expansion of the trinucleotide CAG repeat in the androgen receptor (AR), resulting in the formation of a mutant polyglutamine (polyQ) AR protein. This mutant protein aggregates and causes muscular atrophy, particularly in the limbs and bulbar regions. The weakening of bulbar muscles impacts chewing, speech, and swallowing, often leading to choking or aspiration, which can cause respiratory infections. Limb muscle involvement results in difficulties with walking and a higher risk of falls. Estimates of SBMA prevalence suggest it affects approximately 1 in 6,887 males. Currently, there are no FDA or EMA-approved treatments for SBMA.

AJ201 is a first-of-its-kind treatment aiming to modify SBMA by targeting multiple mechanisms, including the degradation of the abnormal androgen receptor protein and activation of the Nrf1 and Nrf2 pathways, which protect cells from oxidative stress-induced death. A successful Phase 1 study in 72 healthy volunteers demonstrated the safety and pharmacokinetic profile of AJ201. It is now under evaluation in a multicenter, randomized, double-blind Phase 1/2a clinical trial across six U.S. sites, focusing on its safety, pharmacokinetics, pharmacodynamics, and clinical response in SBMA patients. AJ201 has received Orphan Drug Designation from the FDA for SBMA, Huntington’s disease, and spinocerebellar ataxia. Avenue has an exclusive license agreement for AJ201 from AnnJi Pharmaceuticals covering the United States, Canada, European Union, Great Britain, and Israel.

Polyglutamine diseases, including SBMA, involve neurodegenerative conditions caused by expanded CAG repeats that encode long polyQ tracts in the affected proteins. There are currently nine recognized polyQ disorders. The aggregation of mutant proteins in affected tissues is a key pathological feature, with neuroinflammation, oxidative stress, and disrupted protein quality control being major contributing factors. AJ201 aims to mitigate these effects by enhancing the degradation of mutant AR aggregates, inducing antioxidant and heat shock responses, and increasing proteasome expression, making it a promising candidate for treating SBMA and potentially other polyQ diseases.

Avenue Therapeutics specializes in therapies for neurologic diseases, with a current portfolio that includes AJ201 for SBMA, BAER-101 for CNS diseases, and IV tramadol for acute postoperative pain. Based in Miami, FL, and founded by Fortress Biotech, Inc., Avenue continues to focus on addressing unmet medical needs in neurology.