BioWorld International Correspondent

Although Boehringer Ingelheim finally terminated its interest in tesofensine (NS2330), a NeuroSearch A/S drug candidate that had been in development for Alzheimer's disease and Parkinson's disease, NeuroSearch said the compound might have efficacy in obesity.

It now plans to pursue a development program in that indication, and it has started a search for a partner. It also hopes to sign collaborations in Alzheimer's and Parkinson's, on evidence that tesofensine appears to offer potential as a combination therapy.

The alliance with Boehringer Ingelheim, of Ingelheim, Germany, hit the rocks last August, when tesofensine failed to demonstrate efficacy in Phase IIb trials in each indication. Boehringer then decided to discontinue further development in Alzheimer's, but the companies continued to assess the compound's potential in Parkinson's. Under last week's decision, though, Ballerup, Denmark-based NeuroSearch regained all rights to the compound.

"Their evaluation was it could not fulfill what they would require to move to a full Phase III program," NeuroSearch CEO Jorgen Buus Lassen told BioWorld International. (See BioWorld International, Aug. 17, 2005.)

But an analysis of data from 312 obese trial participants, who had either Alzheimer's or Parkinson's, indicated that tesofensine was, on the basis of published data, at least as effective as sibutramine, NeuroSearch said.

The subjects who received 1 mg of drug per day lost an average of 4 kg of body weight during a 14-week treatment period, which, Buus Lassen said, is shorter than most obesity studies.

"We had no dietary restrictions, and patients were not motivated for weight loss," he said. The company conducted supporting preclinical studies in diet-induced obese rats and observed measurable effects of tesofensine on body weight, fat deposition, plasma cholesterol levels and insulin sensitivity. In each of those studies, 2.5 mg/kg of body weight of tesofensine outperformed a 7.5 mg/kg of body weight dose of sibutramine, which is marketed as Meridia by Abbott Laboratories, of Abbott Park, Ill.

Sibutramine blocks reuptake of noradrenaline and serotonin, while tesofensine, a triple monoamine reuptake inhibitor, blocks reuptake of the neurotransmitters dopamine, noradrenaline and acetylcholine.

The involvement of dopamine in influencing the sensation of satiety and thereby influencing body weight has previously been demonstrated with bupropion, marketed by London-based GlaxoSmithKline plc as Wellbutrin for depression and as Zyban for smoking cessation.

"They never pursued it or got it registered," Buus Lassen said.

NeuroSearch plans to move immediately into Phase II trials in obesity and is discussing the study design with a clinical research organization. The company has not yet decided whether to focus the study solely on obesity or to include a subpopulation of diabetics, as well, Buus Lassen said.

The obesity market is bracing itself for a shake-up with the expected approval of rimonabant this year, which developer Sanofi-Aventis Group, of Paris, will market as Accomplia. Annette Rye Larsen, analyst at HSH Gudme in Copenhagen, said NeuroSearch will find it "very easy to attract a partner," given the market's large size and paucity of effective products.

"They definitely need a partner, if not for the Phase II study, definitely for the Phase III," she said. As yet, however, Larsen said she has not put any value on the compound and does not expect it will ever become "a major product" in Parkinson's.

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