Glenmark pain candidate enters human trials

Potential treatment of chronic inflammatory disorders such as osteoarthritis and rheumatoid arthritis (RA)

Glenmark Pharmaceuticals' new chemical entity GRC 27864 is entering human trials, reaffirming the company's position globally in the development of novel pain therapies.

This NCE programme targets Microsomal Prostaglandin E synthase-1 (mPGES-1) as a novel therapeutic target in pain management. GRC 27864 is currently being developed as a drug for the potential treatment of chronic inflammatory disorders such as osteoarthritis (OA) and rheumatoid arthritis (RA). Selective mPGES-1 inhibitors are expected to inhibit increased prostaglandin E2 (PGE2) production in the disease state, without affecting other prostanoid metabolites and, consequently, may be devoid of the gastrointestinal and cardiovascular side effects seen with NSAIDs and COX-2 inhibitors, respectively.

Glenmark has completed preclinical studies and Phase 1 enabling GLP studies and has filed a Phase I application for first-in-human trial with the MHRA in the UK. The Phase 1 studies are to be initiated soon and are likely to be completed by January 2015, the company said. Following this, Glenmark would initiate a proof of concept study in patients with acute pain. 'This is another potential first-in-class molecule and there is a significant unmet medical need,' said Dr Michael Buschle, Chief Scientific Officer, Glenmark Pharmaceuticals.

GRC 27864 is a potent, selective, and orally bioavailable inhibitor of mPGES-1, an enzyme which is up-regulated under inflammatory conditions. Blocking the mPGES-1 enzyme is a novel strategy and expected to selectively inhibit increased PGE2 production during inflammation, without affecting other prostanoids of physiological importance. PGE2 is a potent pro-inflammatory prostanoid and mediator of inflammatory response, which has been implicated in many pathological conditions including inflammation, pain, atherosclerosis, and fever. Thus, GRC 27864 has the potential to be beneficial in the chronic treatment of inflammatory diseases and associated pain.

Recent reports indicate that more than 1.5 billion people worldwide suffer from some form of chronic pain, with a direct correlation between incidence rates and increasing age. It is estimated that, at some point in their lives, 20% of the global adult population suffers from pain with 10% of newly diagnosed cases of chronic pain being added each year.

Despite incremental advances in opioid-based or cyclooxygenase-based therapies, there has been little success in identifying and developing treatments based upon new targets that might overcome the limitations of currently available analgesic treatments for the management of chronic pain, the company added.

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