Treprostinil — a vasodilator — was approved by the U.S. Food and Drug Administration (FDA) in 2002 for the treatment of pulmonary arterial hypertension (PAH). The drug is commercially available as Tyvaso, Orenitram, and Remodulin.
Treprostinil-Technosphere (TreT) is designed to deliver the active ingredient, treprostinil, via a small, novel, portable breath-powered inhaler. The goal is to simplify dosing, and offer PAH patients a more convenient and tolerable treprostinil treatment option.
The trial enrolled 48 healthy individuals, who each received a single dose of Treprostinil inhalation powder daily. The objective was to establish the maximum tolerated dose in these healthy volunteers, starting at 30 mcg and going up to 300 mcg (doses tested: 30, 60, 90, 120, 150, 180, 240, and 300 mcg).
Blood samples were collected from each patient to determine treatment concentrations and pharmacokinetics — the study of the time from drug absorption, distribution, and metabolism to its excretion from the body.
Results showed that progressive dosing of TreT significantly exceeded blood concentration and exposure levels of the maximum recommended dose of Tyvaso (inhaled treprostinil; current standard of care) without causing severe adverse events.
The device successfully delivered the medicine within one or two inhalations and in less than 10 seconds, the company reported.
“I am excited to see that MannKind was safely able to achieve higher plasma levels than reported for the current standard of care using Technosphere-based treprostinil,” Lewis Rubin, MD, emeritus professor of medicine at the University of California, San Diego School of Medicine, said in a press release.
David Kendall, chief medical officer of MannKind, added: “We are pleased to have completed the TreT Phase 1 trial, which met the study’s safety, tolerability and pharmacokinetics objectives. We are excited to utilize our existing technology platform and device capabilities to create an easy-to-use and tolerable formulation of treprostinil to help unmet patient needs in a serious chronic disease such as PAH.”
MannKind is now planning to evaluate the safety, tolerability, and efficacy of TreT combination in patients with PAH.
TreT is being evaluated under an Investigational New Drug (IND) application filed with the FDA.