Avenue Therapeutics Completes Final Patient Visit in AJ201 Clinical Trial for Kennedy's Disease

Avenue Therapeutics, Inc., a specialty pharmaceutical company listed on Nasdaq under the symbol ATXI, announced on May 16, 2024, the conclusion of the last patient's final visit in its Phase 1b/2a clinical trial for AJ201. This trial focuses on treating spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's Disease. The company expects to release the topline data by mid-2024.

Alexandra MacLean, M.D., the CEO of Avenue, expressed excitement about reaching this significant milestone. She extended gratitude to the trial investigators, the patients involved, their partner AnnJi Pharmaceutical Co. Ltd., and the internal Avenue team for their dedication to completing the study on schedule. MacLean emphasized the importance of the promising preclinical efficacy and the excellent clinical safety data from trials in healthy volunteers. The upcoming assessment will focus on AJ201's safety and tolerability in SBMA patients, as well as its impact on potential pharmacokinetic and pharmacodynamic biomarkers, including the degradation of mutant AR proteins in muscles, MRI changes, and neuroinflammation. The company remains committed to advancing AJ201 for SBMA patients, who currently lack effective, approved treatments.

The 12-week Phase 1b/2a clinical trial was conducted across multiple centers and involved 25 patients. These participants were randomly assigned to receive either AJ201 (600 mg/day) or a placebo in a 3:1 ratio. The primary aim was to evaluate the safety and tolerability of AJ201 in individuals with clinically and genetically confirmed SBMA. Secondary objectives included gathering pharmacokinetic and pharmacodynamic data, specifically looking at changes from baseline in mutant AR protein levels in skeletal muscle and alterations in the expression of Nrf2-activated genes in skeletal muscle. Exploratory goals included analyzing changes in fat and muscle composition through MRI scans, which may serve as biomarkers for long-term clinical improvement. More details about the trial can be found on ClinicalTrials.gov under the identifier NCT05517603.

In April 2024, Avenue hosted a virtual key opinion leader event featuring experts in SBMA, including Christopher Grunseich, M.D., and Tahseen Mozaffar, M.D. They discussed the disease characteristics, current treatment landscape, and the potential of AJ201. The event highlighted expert perspectives and the trial design's potential impact on treating SBMA.

SBMA is a rare, genetic neuromuscular disease that primarily affects men. It results from a trinucleotide CAG repeat expansion in the androgen receptor (AR), leading to the production of a mutant polyglutamine (polyQ) AR protein. This abnormal protein forms aggregates that cause muscle atrophy in the limbs and bulbar region, affecting chewing, speech, and swallowing. Patients are at risk of choking or airway infections and may experience difficulty walking and frequent falls. Recent genetic analyses estimate the disease prevalence at 1 in 6,887 males. Currently, there are no FDA or EMA-approved treatments for SBMA.

AJ201, a novel, first-in-class asset, aims to treat SBMA by degrading the abnormal androgen receptor protein and stimulating the Nrf1 and Nrf2 pathways, which protect cells from oxidative stress. Initial Phase 1 trials in 72 healthy volunteers showed excellent safety and pharmacokinetic profiles. The ongoing Phase 1/2a trial across six U.S. clinical sites aims to evaluate AJ201's safety, pharmacokinetics, pharmacodynamics, and clinical responses in SBMA patients. The FDA has granted AJ201 Orphan Drug Designation for several polyQ diseases, including SBMA, Huntington's disease, and spinocerebellar ataxia. Avenue has exclusively licensed AJ201 from AnnJi Pharmaceuticals for use in the U.S., Canada, EU, Great Britain, and Israel.

Avenue Therapeutics is dedicated to developing therapies for neurological diseases, with three main assets: AJ201 for SBMA, BAER-101 for CNS diseases, and IV tramadol for post-operative pain management. Based in Miami, FL, Avenue was founded by Fortress Biotech, Inc.