Date: 2013-04-24
Type of
information: Clinical trial authorisation
phase: 1
Announcement: clinical trial authorization
Company: Addex Therapeutics (Switzerland)
Product: ADX71441
Action
mechanism:
- positive allosteric modulator (PAM). ADX71441 is a GABA-B receptor (GABA-BR) positive allosteric modulator (PAM). ADX71441 is a potent, selective, orally available small molecule that is brain penetrant and shows good pharmacokinetic properties for once-daily dosing. Activation of gamma-aminobutyric acid subtype B (GABA-B) receptor, a Family C class of GPCR, is clinically and commercially validated in several indications including spasticity, overactive bladder (OAB), spinal cord injuries and gastroesophageal reflux disease. However, generic GABA-B receptor agonists are not commonly used in certain disorders due to compliance-limiting drug side effects, receptor sensitization, rebound effect and rapid clearance. An oral once-daily small molecule activator of GABA-B receptor without the issues associated with the current GABA-BR agonists could dramatically change the treatment paradigm for a number of diseases. Allosteric modulation is ideally suited to overcome such limitations of an agonist. ADX71441 has shown efficacy in multiple preclinical models including: CMT1A, OAB, pain, obsessive-compulsive disorder, alcohol binge drinking and anxiety. The United States Patent and Trademark Office recently granted Addex a composition of matter patent covering ADX71441 and other GABA-B receptor PAMs. The claims of the issued patent also cover pharmaceutical composition and method of treatment using such GABA-BR PAMs.
Disease: Charcot-Marie-Tooth 1A disease
Therapeutic
area: Rare diseases - Genetic diseases - Neurological diseases
Country: The Netherlands
Trial
details:
Latest
news:
- • On April 24, 2013, Addex Therapeutics, a Swiss company pioneering allosteric modulation-based drug discovery and development, has announced that the regulatory authorities in the Netherlands have approved the clinical trial application (CTA) to initiate a Phase 1 study of ADX71441, a GABA-B receptor positive allosteric modulator (PAM). The Company plans to initiate clinical testing at the Centre of Human Drug Research in Leiden, in the first half of 2013 and expects to deliver top-line safety, pharmacokinetic and biomarker data by year end. Addex previously announced achievement of positive Proof of Concept for ADX71441 in a validated pre-clinical model of Charcot-Marie-Tooth 1A (CMT1A) neuropathy as well as a number of other disease indications. The Company plans to move quickly to Phase 2a testing of ADX71441 for the treatment of CMT1A, an orphan disease, in 2014. The CTA was submitted to the authorities in March 2013.
- • On January 7, 2013, Addex Therapeutics has announced achievement of a positive Proof of Concept for its lead GABA-B receptor (GABA-BR) positive allosteric modulator (PAM) compound, ADX71441, in a validated pre-clinical model of Charcot-Marie-Tooth 1A (CMT1A). Addex GABA-BR PAM was studied in the transgenic CMT rat model which has 1.6-fold PMP22 overexpression (mRNA level) and exhibits clinical abnormalities, such as reduced nerve conduction velocity and lower grip strength that mimic findings in CMT1A patients. Nine week oral therapy of ADX71441 in CMT rats (5 weeks every other day at 10 mg/kg followed by 4 weeks at 5 mg/kg every day) down regulated PMP22 mRNA, reduced the amount of hypo-myelinated axons and increased compound muscle action potentials in peripheral nerves when compared to vehicle treated CMT rats. It also prevented grip strength loss in CMT rats compared to wild type rats. Phase 1 clinical testing with this compound is now planned for H12013.
Is
general: Yes
