Addex’s Phase IIa study in major depressive disorder fails endpoint

11th February 2014 (Last Updated February 11th, 2014 01:00)

Switzerland-based Addex Therapeutics has reported that a Phase IIa clinical trial of ADX71149 in anxious depression, conducted by Janssen Research & Development on behalf of its affiliate Janssen Pharmaceuticals, failed to meet the criterion for efficacy signal detection versus placebo.

Switzerland-based Addex Therapeutics has reported that a Phase IIa clinical trial of ADX71149 in anxious depression, conducted by Janssen Research & Development on behalf of its affiliate Janssen Pharmaceuticals, failed to meet the criterion for efficacy signal detection versus placebo.

The multicentre, double-blind, placebo-controlled, flexibly-dosed trial was carried out in patients with major depressive disorder (MDD) with significant anxiety symptoms.

In the trial, ADX71149 was well-tolerated and treatment emergent adverse events reported were similar to those seen in previous clinical trials.

Based on a preliminary analysis of the primary efficacy end point, ADX71149 did not meet the six-Item hamilton anxiety subscale (HAM-A6) criterion for efficacy signal detection versus placebo.

"Even though efficacy signals were evident, the data does not support the further development of ADX71149 overall in anxious depression."

The company said that despite a lack of signal on the primary outcome measure, treatment with ADX71149 showed efficacy signals on several anxiety measures and on all depression measures.

The trial will be presented by Janssen at a future scientific meeting and submitted for publication in a peer-reviewed medical journal.

Evaluating efficacy was the primary objective of the trial was, as assessed by change from baseline on a six-item subscale of the HAM-A6, and overall safety and tolerability of treatment with adjunctive ADX71149 compared with placebo in subjects with MDD with anxiety symptoms being treated with an SSRI or SNRI, while secondary outcome measures included those assessing depressed mood, and anxiety.

According to the company, even though efficacy signals were evident, the data does not support the further development of ADX71149 overall in anxious depression and further exploration of the drug candidate in other indications remains of potential interest.

Addex CEO Tim Dyer said the proof-of-concept trial was testing a new mechanism of action in an MDD subpopulation (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 programme," Dyer said.

"In the coming months, we will work with Janssen to identify the best future development path for the programme."

The trial included three phases: a screening phase up to two weeks, an eight-week double-blind treatment phase that included two four-week treatment periods, and a two-week post-treatment follow up phase.

After an initial fixed up-titration from 25mg to 50mg bid, ADX71149 was dosed flexibly in the range of 50mg to 150mg bid.

In the trial, a total of 121 people were enrolled, with 100 subjects (82.6%) completing the eight-week double blind treatment phase.

Addex and Janssen Pharmaceuticals previously signed a worldwide research collaboration and licensing agreement for the development of ADX71149, a novel mGlu2 PAM medication for the treatment of anxiety, schizophrenia and other undisclosed indications.