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12:00 AM
Mar 26, 2007
 |  BioCentury  |  Product Development

Repaving the road

Metabolic Milestones

Repaving the road

While much of the attention on obesity is focused on the July 27 PDUFA date for Acomplia rimonabant, the first-in-class cannabinoid CB1 receptor antagonist from sanofi-aventis Group (Euronext:SAN; SNY, Paris, France), a number of biotech companies have moved past Phase II into late-stage testing with programs that look to improve on existing weight loss drugs.

Other players also have reached later stages of development by using new biological insights to resurrect fallen obesity approaches. And a third leg to the obesity stool includes biotechs that are pursuing drugs that have been developed for other indications in hopes of making obesity therapeutics with well-established safety profiles.

In the late 1990s, FDA approved a pair of drugs for sustained use: Meridia sibutramine, a selective serotonin and norepinephrine reuptake inhibitor from Abbott Laboratories (ABT, Abbott Park, Ill.), and Xenical orlistat, a lipase inhibitor from Roche (SWX:ROG, Basel, Switzerland) and marketing partner GlaxoSmithKline plc (LSE:GSK; GSK, London, U.K.). However, in addition to only moderate effectiveness, each agent has side effects that have limited market penetration.

Xenical is the only approved agent with a distinctly peripheral mechanism. The compound acts as a fat absorption inhibitor by blocking the lipase enzymes in the pancreas from breaking down fat into triglycerides. Unfortunately, this results in oily stool and leakage fecal urgency and flatus with discharge (see BioCentury, Aug. 18, 2003).

Alizyme plc (LSE:AZM, Cambridge, U.K.) and partner Takeda Pharmaceutical Co. Ltd. (Tokyo:4502, Osaka, Japan) hope to improve on orlistat with cetilistat (ATL-926), a next-generation lipase inhibitor that so far has not shown many of the unwanted side effects.

While AZM has not determined exactly how cetilistat avoids many of the unwanted effects of orlistat, Phase IIb data confirm that fewer patients given cetilistat...

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