Geneva, Switzerland, 7 February 2014 - (SIX:ADXN), Addex Therapeutics, a leading company pioneering allosteric modulation-based drug discovery and development, announced today top-line data from a Phase 2a 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 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 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 program."
This was a multicenter, 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 3 phases: a screening phase up to 2 weeks, an 8-week double-blind treatment phase (included two 4-week treatment periods), and a 2-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 8-week double blind treatment phase.
About mGlu2 Activation and ADX71149
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.
About Anxious Depression
Unipolar depression is the leading cause of disability worldwide (2008 WHO Global Burden of Disease Report) and anxiety symptoms are commonly reported in major depressive disorder (MDD) patients. Around 85% of adults with MDD exhibit significant anxiety symptoms (Gorman, 1996); and approximately 50% of outpatients with MDD have a comorbid anxiety disorder, 58% lifetime (Fava et al., 2000; Kessler et al., 1996). Comorbid anxiety results in more severe depressive symptoms, increased suicide risk, more chronic course, poorer and slower treatment response, greater functional and occupational impairment, increased societal burden/socioeconomic costs, and increased health care utilization. The first line treatments for MDD patients with comorbid anxiety are SSRIs and SNRIs, however, this subpopulation is less responsive and continues to demonstrate a great unmet need. Adjunctive treatments to SSRIs/SNRIs for anxious depression result in significant added side effect burden and are often poorly tolerated in long term treatment. The STAR*D clinical study, the largest effectiveness study evaluating next-step therapies in real-world patients with major depressive disorder, showed that patients with anxious depression were less likely to achieve remission or respond to treatment than those with non-anxious depression (Fava et al. 2008).
About Addex Therapeutics
Addex Therapeutics (www.addextherapeutics.com) is a development stage company focused on advancing innovative oral small molecules against rare diseases utilizing its pioneering allosteric modulation-based drug discovery platform. The Company's two lead products are being investigated in Phase 2 clinical testing: dipraglurant (an mGlu5 negative allosteric modulator or NAM) is being developed by Addex to treat Parkinson's disease levodopa-induced dyskinesia (PD-LID) and rare forms of dystonia; and ADX71149 (mGlu2 positive allosteric modulator or PAM) is being developed in collaboration with Janssen Pharmaceuticals, Inc. Addex also has several preclinical programs including: GABAB receptor positive allosteric modulator (PAM) for Addiction, Charcot-Marie-Tooth (type 1a) disease, spasticity in patients with multiple sclerosis (MS), pain, overactive bladder and other disorders; and mGlu4 PAM for MS, Parkinson's disease, anxiety and other diseases. Allosteric modulators are an emerging class of small molecule drugs which have the potential to be more specific and confer significant therapeutic advantages over conventional "orthosteric" small molecule or biological drugs. The Company uses its proprietary discovery platform to target receptors and other proteins that are recognized as essential for the therapeutic modulation of important diseases with unmet medical needs.
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Disclaimer: The foregoing release may contain forward-looking statements that can be identified by terminology such as "seek", "not pursue", "not approvable", "continue", "believes", "believe", "will", "remained open to exploring", "would", "could", or similar expressions, or by express or implied discussions regarding Addex Therapeutics, formerly known as, Addex Pharmaceuticals, its business, the potential approval of its products by regulatory authorities, or regarding potential future revenues from such products. Such forward-looking statements reflect the current views of Addex Therapeutics regarding future events, future economic performance or prospects, and, by their very nature, involve inherent risks and uncertainties, both general and specific, whether known or unknown, or any other factor that may materially differ from the plans, objectives, expectations, estimates and intentions expressed or implied in such forward-looking statements. Such factors may in particular cause actual results with allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR or other therapeutic targets to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Addex Therapeutics will complete the restructuring and reduction of its liabilities or any financing nor that allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR or other therapeutics targets will be approved for sale in any market or by any regulatory authority. Nor can there be any guarantee that allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR or other therapeutic targets will achieve any particular levels of revenue (if any) in the future. In particular, management's expectations regarding allosteric modulators of mGlu2, mGlu4, mGlu5, GABA-BR or other therapeutic targets could be affected by, among other things, unexpected actions by our partners, unexpected regulatory actions or delays or government regulation generally; unexpected clinical trial results, including unexpected new clinical data and unexpected additional analysis of existing clinical data; competition in general; government, industry and general public pricing pressures; the company's ability to obtain or maintain patent or other proprietary intellectual property protection. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Addex Therapeutics is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise, except as may be required by applicable laws.