Glenmark's TRPA1 Antagonist Shows Promise In Phase 2 Trial For Diabetic Neuropathy
By C. Rajan, contributing writer
Glenmark Pharmaceuticals last week announced positive results for its first-in-class Transient Receptor Potential Ankyrin 1 (TRPA1) antagonist, GRC 17536, in a Phase 2a study for treating diabetic neuropathy.
The double blind, placebo controlled, multi-center, proof of concept Phase 2a study was conducted on 138 patients in Europe and India. A statistically significant and clinically relevant response was seen in patients with moderate to severe pain who had relatively intact sensory responses. GRC 17536 was well-tolerated with no evidence of CNS or other drug related side effects.
Diabetic neuropathy is a common complication among diabetes patients, which causes nerve damage. The symptoms can range from severe pain to a loss of sensation in legs and feet.
Patrick Keohane, CMO of Glenmark, stated, "Diabetic neuropathy remains a difficult to manage chronic clinical condition with limited therapeutic options. These initial efficacy and safety data with GRC 17536, a peripherally acting novel therapeutic, are encouraging, and Glenmark intends to be ready to file for a Phase 2b dose range finding study in patients with neuropathic pain before the end of this financial year. This announcement also reaffirms our position globally in the development of novel pain therapies."
GRC 17536 is a potent, selective antagonist of TRPA1 receptor. The TRPA1 receptor is known to induce pain hypersensitivity in models of diabetic neuropathic pain. Blocking this receptor can reduce pain hypersensitivity as well as prevent damage of the nerve fibers and their function.
Preclinical studies on GRC 17536 have demonstrated its effectiveness in animal models of neuropathic and inflammatory pain including the peripheral diabetic neuropathic pain, osteoarthritic pain, postoperative pain and chemotherapy-induced pain, which supports potential utility of TRPA1 blockade in therapeutic pain management.
Glenmark’s TRPA1 program includes indications in pain management as well as respiratory conditions. Inhaled doses of GRC 17536 are also being tested in a Phase 2A proof of concept study in patients with chronic cough.
India-based Glenmark is a leading global pharmaceutical company, which is developing new drugs as well as generics. Glenmark has several new molecules in various stages of clinical development and is primarily focused in the areas of inflammation, pain, and oncology. The company recently opened a new U.S. manufacturing facility in North Carolina for manufacturing oral drugs, injectables, and topical drugs for the U.S. market. Earlier in June, Glenmark also opened a new cGMP compliant monoclonal antibody manufacturing facility in La Chaux-de-Fonds, Switzerland.