Addex Therapeutics, a leading company pioneering allosteric modulation-based drug discovery and development, has reported top-line data from a phase IIa clinical study of ADX71149 in anxious depression, conducted by Janssen Research & Development, LLC, on behalf of its affiliate Janssen Pharmaceuticals, Inc. Overall, ADX71149 was well-tolerated and treatment emergent adverse events reported were similar to those seen in previous clinical studies.
Based on a preliminary analysis of the primary efficacy end point, the 6-Item Hamilton Anxiety Subscale, (HAM-A6), ADX71149 did not meet the criterion for efficacy signal detection versus placebo. The placebo response was considered acceptable. Despite a lack of signal on the primary outcome measure, treatment with ADX71149 showed efficacy signals on several anxiety measures (HDRS17 anxiety somatization factor, IDS-C30 anxiety subscale) and on all depression measures (HDRS17, HAM-D6 and IDS-C30). This study will be presented by Janssen at a future scientific meeting and submitted for publication in a peer-reviewed medical journal.
Although efficacy signals were evident, overall the data does not support the further development of ADX71149 in anxious depression. Further exploration of ADX71149 in other indications remains of potential interest.
"This proof-of-concept study was testing a new mechanism of action in an MDD sub-population (anxious depression) that had not been studied in clinical trials to date. We greatly appreciate the efforts and resources that our partner, Janssen has deployed to further our understanding of this mechanism and advance the program," said Tim Dyer, CEO at Addex. "In the coming months we will work with Janssen to identify the best future development path for the programme."
This was a multi-centre, double-blind, placebo-controlled, flexibly-dosed study of adjunctive ADX71149 in adults with Major Depressive Disorder (MDD) with significant anxiety symptoms. The primary objective was to evaluate efficacy, as assessed by change from baseline on a 6-item subscale of the Hamilton Anxiety Scale (HAM-A6), and overall safety and tolerability of treatment with adjunctive ADX71149 compared to placebo in subjects with MDD with anxiety symptoms being treated with an SSRI or SNRI. Secondary outcome measures included those assessing depressed mood (HDRS17; IDS-C30, HAM-D6), and anxiety (HAM-A-14; HDRS17 anxiety somatization factor, IDS-C30 anxiety subscale).
The study consisted of three phases: a screening phase up to two weeks, an eight-week double-blind treatment phase (included two four-week treatment periods), and a two-week post-treatment (follow up) phase. Following an initial fixed up-titration from 25mg to 50mg b.i.d, ADX71149 was dosed flexibly in the range of 50mg to 150mg b.i.d. Of the 121 randomized subjects, 100 subjects (82.6%) completed the eight-week double blind treatment phase.
ADX71149 is a novel, first-in-class potent, oral, small molecule positive allosteric modulator (PAM) of metabotropic glutamate receptor 2 (mGlu2), a Family C class of G Protein Coupled Receptor (GPCR). The development of ADX71149 is part of a worldwide research collaboration and license agreement between Addex and Janssen Pharmaceuticals, Inc. to discover, develop and commercialize a novel mGlu2 PAM medication for the treatment of anxiety, schizophrenia and other undisclosed indications. Under the terms of the agreement, Addex is eligible for up to a total of €112 million in milestone payments based on potential development and regulatory achievements. In addition, Addex is eligible for low double-digit royalties on sales of any mGlu2 PAM medication developed under the agreement.
Addex Therapeutics is focused on advancing innovative oral small molecules against rare diseases utilizing its pioneering allosteric modulation-based drug discovery platform.