Tuesday, April 14, 2009

Glenmark completes phase I trial of GRC 10693 in Europe

Mumbai- Glenmark Pharmaceuticals Limited (GPL) has successfully completed phase I trials of its candidate for neuropathic pain, osteoarthritis and other inflammatory pain disorders - GRC 10693 in Europe.

The phase I study was conducted on 80 healthy human subjects using escalating single and multiple oral doses with the objective of assessing safety, tolerability and pharmacokinetics of GRC 10693. The highest single dose achieved in the study was 1200 mg. The study demonstrated that GRC 10693 was well tolerated by the subjects at all dose levels and was found to have a dose proportional pharmacokinetic profile with good exposure levels.

There were no serious or significant adverse events, including no significant cardiovascular effects or QT prolongation seen in either the single dose or the multiple dose cohorts. The latter cohort received 300mg of GRC 10693 once daily for 14 days and achieved exposure levels equivalent to those in the highest tested single dose.

Speaking on this development, Glenn Saldanha, MD & CEO, GPL, said, "This is a significant achievement for our organization as GRC10693 will be our fourth molecule which will enter phase II trials. He further added "We are very excited with the results from the phase 1 studies of GRC 10693. It offers a novel treatment approach to pain and has attracted a lot of scientific and commercial interest. By being successful in an area where very few molecules have passed to the clinical development stage, it also reinforces Glenmark's capability in advancing drugs with first-in-class potential."

In the phase 1 studies, high exposure levels of the drug were reached, which exceeded by several folds the levels required for efficacy in various in vivo acute and chronic pain models in animals. In addition, several well validated pain models included in the study for confirmation of Proof of Mechanism in the multiple dose phase, demonstrated significant improvements in various pain scores at both 2 and 13 days, the key efficacy time points defined in the protocol. This combination of a very good safety profile and pharmacokinetics, combined with good Proof of Mechanism results, marks a very promising start to the clinical development of GRC 10693.

Initially, the company intends to develop GRC 10693 in neuropathic pain as the primary indication, with phase IIb trials planned to be initiated later this year.

GRC 10693 is the only selective cannabinoid-2 [CB-2] receptor agonist currently reported in clinical development following oral route of administration and has first-in-class potential. GRC 10693 has above 4700-fold functional selectivity for CB2 over CB1 making it one of the most selective CB2 agonist reported in development.

Dr John Efthimiou, president clinical R&D & CMO of Glenmark was delighted at this development and explained that "The design of this phase 1 study allowed us to establish a very good therapeutic window by evaluating not just the pharmacokinetics and safety, but also by obtaining an early read on the Proof of Mechanism. For a novel target, this data validates the approach and opens the path for us to expedite subsequent development with substantial confidence."

GRC 10693 is potentially a first-in-class molecule, with block buster potential and is likely to be an early launcher in this class of compounds with a target launch date of 2014. The molecule is a novel, potent and selective human cannabinoid (CB-2) receptor agonist, with over 4700-fold selectivity over the CB-1 receptor and good bioavailability across species tested. There is a large un-met medical need and the recent concerns around the safety of cox-2 inhibitors should propel sales of safer products. The neuropathic pain market is estimated at around USD 5 billion with over 40 million patients worldwide while the osteoarthritis market is valued at over USD 4 billion with over 20 million patients.

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