New Class Of Highly Selective 5-HT4 Receptor Agonists Provides The Next Generation Of GI Treatments

Main Category: GastroIntestinal / Gastroenterology
Also Included In: Pharma Industry / Biotech Industry
Article Date: 31 Jan 2008 - 1:00 PDT

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A scientific review of the different pharmacological profiles of 5-HT4 receptor agonists published in Neurogastroenterology and Motility concludes that, due to a more selective mode of action, next-generation 5-HT4 compounds are expected to be safer and more effective treatment options for common, debilitating gastrointestinal (GI) motility disorders such as chronic constipation (CC) and gastroparesis1.

"Millions of people - adults and children - suffer from common, debilitating GI conditions that are caused by impaired motility," commented Jan Schuurkes, Chief Scientific Officer, Movetis NV, Belgium. "This research supports that the next generation of 5-HT4 receptor agonists has the potential to offer superior selectivity in the treatment of a variety of motility disorders and we are confident that these compounds have the potential to meet the needs of many doctors and patients seeking a more effective and safer prokinetic treatment."

Research in the last decade has focused on the development of high-affinity 5-HT4 receptor agonists designed to be free of the side effects associated with older-generation, nonselective compounds, such as cisapride and tegaserod. It is now known that 5-HT4 receptor agonists differ substantially, not only in their selectivity for other receptors or channels, but also in their interaction with the 5-HT4 receptor itself. Combined, these two properties support why next-generation, selective, 5-HT4 receptor agonists are expected to better target the GI system alone, resulting in greater safety for patients.

According to the authors of this review, Prof. Romain A Lefebvre (Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium) and Joris H De Maeyer, PhD (Movetis NV, Belgium), 'We have known for a long time that 5-HT4 receptor agonists have considerable therapeutic potential for patients with motility disorders. Unfortunately, older generation drugs in this class have a high affinity for other tissue receptors or channels which, in some cases, can lead to adverse side effects, and thereby result in a negative perception of these drugs and confusion about their risk-benefit profile.'

RESOLOR® (prucalopride) is currently the most advanced selective, high-affinity 5-HT4 receptor agonist in research1. It belongs to a new chemical class of 5-HT4 agonists that elicits responses in many GI tissues. Through this more selective approach, RESOLOR® appears to offer patients a novel enterokinetic treatment that increases colon motility and restores the slow movement of the bowels. This scientific review and the latest results from Phase III clinical trials evaluating the safety and effectiveness of RESOLOR® in patients with CC for whom laxatives do not provide adequate relief2 suggest that the compound has an attractive safety profile, making it a promising candidate for the treatment of this condition.

About Movetis

Through a clear focus on GI, Movetis seeks to improve the lives of millions of patients - both adults and children - by discovering, developing and commercialising innovative treatments targeting GI conditions that have recently benefited less from innovation. Movetis NV - founded in Belgium in December 2006 - aims to become the leading European specialty pharmaceutical organisation focused on GI diseases. Movetis has a broad GI portfolio with four products in clinical development and four in preclinical, all aiming to address important areas of unmet medical need, including chronic constipation (CC), ascites, paediatric reflux, diabetic gastroparesis, specific subgroups of patients with severe forms of IBS or dyspepsia and secretory diarrhoea. In addition, Movetis has rights to a large library of qualified lead compounds with potential for development. The current portfolio has been licensed from Janssen Pharmaceutica NV, Belgium and Ortho-McNeil Pharmaceutical Inc., two Johnson & Johnson (J&J) companies.

The current clinical portfolio includes:

- RESOLOR® (prucalopride), a compound for the treatment of CC currently in preregistration

- M0002, a compound for the treatment of ascites, which has completed recruitment of a Phase IIa trial; results are expected before the end of Q2 2008

- M0003, a gastrokinetic compound for the treatment of paediatric reflux and gastroparesis, which has recently entered Phase IIa clinical trials in gastroparesis

- M0004, another gastrokinetic compound for nocturnal heartburn and other motility complaints related to gastro-oesophageal reflux disease (GORD).

In 2006, Movetis secured 49 million Euros in a series 'A' financing from major European and US investors - one of the biggest series 'A' rounds in Europe. These funds are being used to complete the development and registration filing of RESOLOR, and to continue preclinical and clinical development of all other products. Investors include Sofinnova Partners, J&J, Life Sciences Partners, Sofinnova Ventures, KBC Private Equity and KBC Private Equity Fund Biotech, GIMV, Quest for Growth and BIP Investment Partners. In a further boost to its commitment to bring innovation back to GI, Movetis was granted 1.67 million Euros by the Institute for the Promotion of Innovation by Science and Technology in Flanders (IWT) at the end of 2007 to support early and innovative development for M0002 and to start discovery efforts with its library of 5-HT4 agonists. Movetis is based in Turnhout, Belgium.

References

1. De Maeyer J, Lefebvre R, Schuurkes J. 5-HT4 receptor agonists: similar but not the same. Neurogastroenterology and Motility 2008;20(2):99-112.

2. Tack J, Tan G, Vandeplassche L A randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety of prucalopride in patients with chronic constipation. Abstract OP-G-377, UEGW 2007.

Movetis NV