Glenmark claims TRPA1 antagonist is ahead of competition as it moves to Phase II
This article was originally published in Scrip
Glenmark Pharmaceuticals hopes to initiate Phase IIa proof-of-concept studies in Europe by March for its TRPA (transient receptor potential ankyrin) 1 receptor antagonist for painful diabetic peripheral neuropathy, GRC 17536, potentially making the molecule the most advanced in its class.
"GRC 17526 is the only TRPA1 antagonist in the clinic now. [The] Hydra programme is yet to enter Phase I clinical trials. GRC 17536 is a very potent, highly selective compound showing very promising animal PoC," Glenmark told Scrip. It offered no direct comparison with Cubist Pharmaceuticals/Hydra Biosciences' competing molecule since it does not have much publicly available information on the compound.
In January this year, the two US firms said that they expected to begin a Phase I clinical trial for their selective TRPA1 antagonist, CB-189,625, and had filed for IND approval. The open-label, dose-escalation study to assess the safety and pharmacokinetics of CB-189,625 in healthy volunteers will be done in the Netherlands and is expected to start in the first quarter.
GRC 17536 has already completed Phase I trials in the Netherlands. In studies for both the single ascending dose and multiple ascending doses, the drug was well tolerated up to the maximum dose tested. It also displayed a good pharmacokinetic profile with no apparent gender or age effect, which suggests a less complex development programme and a more acceptable drug profile, Glenmark said.
"The overall exposures achieved in humans compare favourably with the exposure required for maximum efficacy in the animal models, which suits entry into further clinical development," a statement from the Indian firm noted.
Glenmark has filed regulatory submissions with the UK MHRA and BfArM in Germany to initiate a Phase IIa proof-of-concept study in patients with painful diabetic peripheral neuropathy. The double-blind, parallel group, placebo controlled trial is designed to provide efficacy endpoints upon several weeks of dosing and the company hopes to start by March, subject to regulatory approvals.
respiratory indication
Glenmark also plans to test GRC 17536 for use in respiratory indications. It said that good efficacy had been observed for GRC 17536 when administered via the inhaled route in preclinical pharmacology studies and that Phase I enabling toxicity studies were close to completion.
The firm aims to initiate human inhalation studies by June 2012 with an integrated phase I/IIa protocol in healthy adult volunteers and mild asthmatics, followed by an allergen challenge study in patients with mild asthma. These studies are being planned to be conducted in the UK.
Recent studies suggest that TRPA1 antagonists may have potential in the treatment of asthma, chronic cough and possibly other inflammatory conditions of the airways, including chronic obstructive pulmonary disease and reactive airway dysfunction syndrome.
In 2010, the Indian company licensed a series of TRP vanilloid 3 antagonists for chronic pain to Sanofi.