AV650 (Treatment of Disabling Neuromuscular Spasm and Spasticity)
AV650 is an orally administered, centrally acting small molecule marketed for the treatment of muscular spasm and spasticity in Europe and Asia. Avigen is developing AV650 for the North American market under a license and supply agreement with a subsidiary of Sanochemia Pharmazeutika AG.
The mode of action of tolperisone is not fully characterized, but it appears to be primarily via inhibition of spinal reflex pathways. It suppresses mono- and poly-synaptic reflex transmission by pre- and post-synaptic mechanisms, especially in pathologically increased reflexes. It causes a frequency-dependent decrease in action potential amplitude. Tolperisone has Na+ channel blocking activity. It inhibits voltage-gated Na+ channels in a relatively selective manner; however, even at high concentrations the blockade remains incomplete and reversible.
An IND was successfully filed in May 2006, and a Phase I double blind placebo controlled safety and Pk study in 30 healthy volunteers was completed in September 2006. In this one-week study, AV650 was well tolerated by study subjects as there were no Significant Adverse Events(SAEs), and the mild AEs occurring during the study resolved without intervention. Additionally, no significant sedation or cognitive changes were seen.
Avigen is conducting two AV650 Phase II trials: for patients with spasticity following spinal cord injury, and for patients with spasticity associated with multiple sclerosis.
Avigen's development program will build on the extensive ex-U.S. safety and efficacy experience with this compound (Pratzel 1996, Stamenova-etal 2005, Dulin 1998, Feher-etal-1985 [see Research & Development - "Publications" list]). AV650 is an important potential therapy for disabling neuromuscular spasms. AV650’s established record of successful use and safety in many international markets helps support the benefits it can provide as a fast-acting muscle relaxant without sedation or alcohol interaction.