FDA Request on Capsule Manufacturing Delays Phase 2b Trial of Tesomet

A planned Phase 2b trial of Tesomet in treating Prader-Willi syndrome (PWS) is being pushed back to later this year, following a request from the U.S. Food and Drug Administration (FDA) for more information on the medication’s manufacturing.

“While we are disappointed to delay the initiation of our Phase 2b clinical trials of Tesomet in PWS and [hypothalamic obesity], we are encouraged that we have clear agreement from the FDA regarding our development plans as they relate to the manufacturing of these new Tesomet capsules,” Kyle Haraldsen, chief technical operations officer for Saniona, Tesomet’s developer, said in a press release.

Saniona has transitioned to producing Tesomet as capsules, rather than tablets, as people with PWS have a tendency to chew the tablets, which reduces their effectiveness. The capsules contain Tesomet’s two active ingredients — tesofensine and metoprolol — within microspheres. Chewing and biting is expected to be less disruptive to the fixed-dose combination in this format.

The company requested FDA feedback regarding their manufacturing plans before initiating a series of planned clinical trials.

While the agency agreed with Saniona’s plans related to the proposed Phase 2b trial, it requested more information on capsule manufacturing. No additional trials are needed to obtain this information, but gathering the data will delay the trial’s start.

“We believe that the work we are doing to optimize Tesomet and align with the FDA on manufacturing will enable us to move more expeditiously through our clinical trials, so that we may bring Tesomet to patients as quickly as possible,” Haraldsen said.

The FDA had previously granted Tesomet orphan drug designation, meant to speed a potential therapy’s path to market, based on the results of a Phase 2a study (NCT03149445). Patients taking Tesomet at 0.25 mg in this study saw an average 69% decrease in hyperphagia — uncontrollable hunger — over its course.

A higher, 0.5 mg dose, further associated with clinically meaningful weight loss among adolescents and adults with PWS.

In Tesomet, tesofensine stops nerve signals by preventing nerve cells from reabsorbing (effectively recycling) certain messenger molecules. As tesofensine may induce irregular heart rhythms, metoprolol is used to improve circulation and lower blood pressure.

Saniona has worked with PWS advocacy organizations to inform patients and their families of the trial, which had been expected to open by mid-year; that opening is now likely for the second half of 2021.

The company is also evaluating Tesomet’s potential to treat hypothalamic obesity, which also features an abnormal sensation of hunger. A separate Phase 2b trial for that indication is also delayed until later this year, to comply with the FDA request.