Product News: Addex Reports Top-line Data from a Successful Phase 2a Clinical Study with ADX71149 in Schizophrenia Patients

05 Nov 2012

Addex, a leading company pioneering allosteric modulation-based drug discovery and development, has announced top-line data from a successful Part B of the first-in-patient Phase 2a clinical study of ADX71149 in schizophrenia. The research was conducted by Janssen Research & Development, LLC, on behalf of its affiliate Janssen Pharmaceuticals Inc. The data show that ADX71149 met the primary objectives of safety and tolerability. ADX71149 also demonstrated an effect in patients with residual negative symptoms. The 50mg b.i.d. dose was identified as having the optimal benefit/risk ratio in this study.

ADX71149 is an oral, selective, small molecule, positive allosteric modulator (PAM) of the metabotropic glutamate receptor 2 (mGluR2), a Class C G-Protein Coupled Receptor (GPCR), with potential to be used in the treatment of schizophrenia and the treatment of anxiety in patients suffering from major depressive disorder.

This first-in-patient study is being conducted in the EU, to determine the safety and tolerability of ADX71149 and to explore the potential clinical effect of this mGluR2 PAM in patients with schizophrenia. The study has two concurrent parts (A and B) and is designed to identify the patient populations most likely to benefit from treatment with ADX71149.

Part A: Safety, tolerability and efficacy of ADX71149 as monotherapy in the treatment of patients with sub-acute psychosis. This is a 12 week open-label treatment in 15 patients not on antipsychotic medication. Dose range from 50 mg b.i.d titrated up to 150 mg b.i.d. Part A is ongoing.

Part B: ADX71149 as adjunctive therapy to antipsychotics. This part of the study for which top-line data are being reported today, was a randomized double-blind, placebo-controlled trial designed to evaluate the safety, tolerability and exploratory efficacy of ADX71149, in 92 patients who were on stable doses of antipsychotic medication. The study population comprised 3 groups: patients with residual negative symptoms (n = 47); patients with residual positive symptoms (n = 25); and patients with insufficient response to clozapine treatment (n = 20). For the first 4 weeks of treatment all patients were randomized to receive either ADX71149 50 mg b.i.d, ADX71149 150 mg b.i.d or placebo, taken concomitantly with their currently prescribed antipsychotic medication (randomized 2:2:1).

"I am delighted that the study achieved its objectives of demonstrating good safety and tolerability and identifying the population of schizophrenia patients most likely to benefit from adjunctive treatment with ADX71149," noted Dr. Charlotte Keywood, CMO at Addex.

Negative symptoms (typically comprising apathy, social withdrawal, loss of emotional expression and sleep disorders) are common, and occur in up to 90% of patients with schizophrenia. Currently available drugs do not always provide effective control and many patients remain with substantial disability as a result. Therefore, effective treatment of negative symptoms is a major unmet medical need in the management of schizophrenia.

"We are extremely proud of our partnership with Janssen and greatly appreciate their continued commitment towards advancing ADX71149 and our mGluR2 PAM program in these psychiatric indications with significant unmet medical need," said Dr. Bharatt Chowrira, CEO at Addex. "These top-line results are a significant achievement for Addex and serve as further validation for our innovative oral small molecule allosteric modulation drug discovery technology platform."

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 novel mGluR2 PAM 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 upon potential development and regulatory achievements. In addition, Addex is eligible for low double-digit royalties on sales of mGluR2 PAM developed under the agreement.