Productos Medix S.A. de C.V., a Mexican weight loss specialist leading the most advanced effort to date to get Danish drug developer Saniona AB's first product to market, started a phase III trial of the drug, tesofensine, in obesity. The Medix-funded study is due to finish within two years and could potentially support approval of the triple monoamine reuptake inhibitor as a monotherapy in Mexico, where it's estimated that more than 70 percent of people are overweight and more than 30 percent are clinically obese.

If approved in Mexico, sales of tesofensine could help Medix recover from its loss of an exclusive regional distribution deal with Medifast Inc. earlier this year while also generating key clinical data for Tesomet, a fixed-dose combination of tesofensine and the beta blocker metoprolol. Medix has exclusive rights to develop and commercialize both tesofensine and Tesomet in Mexico and Argentina.

Tesofensine's pound-shedding potential first came to light in 2005 during its development as a potential treatment for Alzheimer's and Parkinson's diseases by Neurosearch A/S, where the candidate was known as NS-2330.

A midstage trial called TIPO-1 confirmed the effect in late-2007, showing that patients lost up to an average of 11.3 kg (24.9 lb) on a 0.5 mg dose of the drug and 6.7 kg (14.8 lb) on a 0.25 mg dose vs. a 2.2 kg (4.9 lbs) loss in the placebo group.

"Neurosearch was considering going all the way with the drug," Jørgen Drejer, CEO and founder of Saniona, told BioWorld. "But it turned out that there was also a slight increase in heart rate with tesofensine and, for that reason, it became more complicated with clinical studies and regulatory, leading them to stop the [drug's] development."

Though there's potential for Mexican authorities to red flag the heart rate issue, they so far haven't done so, according to Drejer.

Cardiovascular concerns and the requisite big and expensive safety trials usually required to address these issues have derailed many a weight loss drug. But Drejer, once director of research at Neurosearch and its co-founder, as well, found a path forward with Tesomet. The combination with metoprolol avoids the affect on the heart rate, creating what he said is "an extremely safe drug" that could be used not only in obesity but also in more complicated metabolic disorders, like type 2 diabetes and Prader-Willi syndrome (PWS).

In January, Ballerup, Denmark-based Saniona reported top-line results from its phase IIa trial of Tesomet in patients with type 2 diabetes, with the primary endpoint showing a statistically significant reduction in heart rate for patients treated with Tesomet vs. placebo. The key secondary and exploratory endpoints regarding body weight and waist circumference also showed statistically significant reductions compared to placebo. Glycemic secondary endpoints were not statistically significantly different from placebo. The trial approximated the final formulation of Tesomet with two separate pills, so Saniona now is preparing to run a phase I trial with its single-pill formulation in an obese population that includes diabetic patients.

In parallel, the company initiated a phase IIa study in the Czech Republic and Hungary in PWS, a genetic disorder that causes obesity. If successful, that indication could pave a faster and cheaper path that the company could potentially take all the way to market on its own, Drejer said.

Meanwhile, the randomized, double-blind, placebo-controlled, parallel-arm study of tesofensine is getting underway in Mexico. Medix will recruit up to 372 ambulatory adults with obesity, randomizing them into three arms, each including 124 patients. Patients will receive either a 0.25-mg or 0.5-mg dose of tesofensine or placebo tablets once daily for 24 weeks. But first, they'll go through the study's two-week run-in period, during which they'll receive nutritional and exercise counseling.

The first group of patients has started the run-in period and will be randomized to one of the treatment arms or placebo later this month.

The primary endpoint of the trial is absolute and percent change in body weight over the treatment period. Secondary endpoints include proportions of patients achieving a weight loss of more than 5 and 10 percent, respectively, metabolic endpoints that include glycemic measures and quality of life, comprehensive tolerability and safety metrics.