Tenax Acquires Rights to Oral Levosimendan, Plans Phase 3 Trial in Type 2 PH

Tenax Therapeutics  has acquired developmental and commercial rights for North America to an oral formulation of levosimendan, a potential therapy for pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF).

Tenax plans to open a Phase 3 safety and efficacy trial of oral levosimendan in patients with PH-HFpEF, a form of PH related to left heart disease (type 2) for which there are no approved therapies.

“Adding the oral formulation to our existing agreement represents a significant opportunity for us. Use of the currently available 1 mg capsule of levosimendan should allow us to conduct our upcoming Phase 3 trial with significantly faster enrollment versus the IV [intravenous] formulation,” Anthony DiTonno, CEO of Tenax, said in a press release.

Initially developed to treat heart failure, levosimendan is a calcium sensitizer that promotes heart contraction without increasing oxygen demand. The therapy also has a protective effect on the heart muscle, promotes blood vessel widening, and improves blood flow and oxygenation. In its intravenous form, it is available as Simdax in nearly 60 countries, but not the U.S., to treat acute heart failure.

Under a licensing agreement signed with Orion Corporation in 2013, Tenax acquired developmental and commercial rights of intravenous levosimendan for the U.S. and Canada. The expanded license agreement, called an amendment, extends those rights to the medication as an oral formulation.

The amendment also gives the company access to all the manufacturing, preclinical, and clinical data currently available for  oral levosimendan, a capsule formulation. That oral form has already been tested in a large number of patients, many for up to one year, the company reported.

One such trial was the REFALS (NCT03505021) study, in which 492 people with amyotrophic lateral sclerosis (ALS) were given levosimendan as 1 mg capsules once or twice daily for 48 weeks. Treatment was seen to be safe, but the trial failed to meet its primary goal of better respiratory and overall function in these patients.

Tenax recently completed a Phase 2 trial, called HELP (NCT03541603), assessing the safety and efficacy of intravenous levosimendan in patients with PH-HFpEF.

Data from this study showed that, compared with a placebo, levosimendan significantly reduced pulmonary capillary wedge pressure (PCWP) — a measure of blood pressure on the left side of heart — at rest, and improved patients’ physical capacity, as seen in increased distances covered in the six-minute walk test.

Treatment with intravenous levosimendan was also found to be safe and well tolerated.

“We expect an oral formulation will also enable us to enjoy greater market acceptance upon FDA approval for marketing,” DiTonno said.

Tenax intends to review its plans for oral levosimendan’s use in a future Phase 3 trial during its End-of-Phase 2 meeting with the U.S. Food and Drug Administration.