Glenmark Pharmaceuticals Ltd., a Mumbai based research-led, global, fully integrated pharmaceutical company, announced that its candidate for rheumatoid arthritis, inflammation and multiple sclerosis - GRC 4039, has entered phase I trials. This is with approval from the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK.
According to a Glenmark press release, the company intends to develop GRC 4039, a PDE 4 inhibitor, in rheumatoid arthritis as the primary indication. Glenmark expects to complete phase I trials for GRC 4039 by October 2008 and initiate phase II by January 2009.
GRC 4039, a selective PDE4 inhibitor is intended for rheumatoid arthritis [RA] and inflammatory disorders. After the withdrawal/setback of COX-2 inhibitors and the void that exists in RA therapy for orally available potent small molecules, this is a potential block-buster opportunity in the global market.
Speaking on this development, Glenn Saldanha, MD & CEO, Glenmark Pharmaceuticals Ltd., said, "We are happy to take GRC 4039 forward into phase I trials. This is Glenmark's fourth molecule to enter the clinics from our pipeline of eight NCEs and NBEs, and demonstrates our steady progress in the drug discovery space. RA has been selected as the primary indication for its commercial attractiveness, the unmet medical need for potent and convenient oral therapies and the sound biological rationale for PDE-4 inhibitor-based treatment in RA."
GRC 4039 in pre-clinical testing has exhibited IC50 of 2.7nM; over 3700 fold selectivity to PDE4, good bioavailability across species and a long half-life indicating the potential for a once-daily dosing regimen. Additionally, there was no emesis in the pre-clinical models. The molecule demonstrated favourable results in early toxicology studies, a good safety margin and also exhibited good efficacy in in-vivo RA and TNF- ? inhibition models.
RA is a debilitating disorder with significant unmet need and attractive market dynamics. Approximately 1 per cent of the global population is thought to be affected by the disorder, a systemic autoimmune disease that usually causes progressive symmetrical inflammation and damage of the joints by destroying the articular surfaces covering the bones. One in three RA patients is likely to be disabled within 20 years of disease onset due to rapid disease progression. Onset often occurs between the ages of 25 and 50 years and is two to three times more prevalent in women than in men.