Phase 1 Trial Results Support Powder Formulation of Treprostinil Advancing to Phase 3 Studies, Liquidia Says
Results of a Phase 1 clinical trial of Liquidia Technologies’ powder formulation of treprostinil for pulmonary hypertension were promising enough to advance it into Phase 3 trials, the company reports.
The trial included 57 healthy volunteers who randomly received escalating doses of the therapy, LIQ861, ranging between 25 mcg and 150 mcg, or a placebo. Single administration of LIQ861 was found to be safe and well tolerated in all tested doses, and no serious adverse events were reported.
Another finding was that 100 mcg and 150 mcg of LIQ861 stayed in the blood as long as four hours in about half of the participants. This suggested that LIQ861 has the potential to manage symptoms effectively between dosing cycles.
Preclinical-trial studies had shown LIQ861 to be as effective as treprostinil solution administrated as a mist. And there was no evidence of treprostinil accumulating with repeated exposure.
The results of the pretrial study and the Phase 1 trial were the subject of a presentation called “Preclinical and Phase 1 Clinical Characterization of LIQ861, a New Dry Powder Formulation of Treprostinil” in Singapore, Jan. 21-24. It was delivered at the 12th Pulmonary Vascular Research Institute Annual World Congress on Pulmonary Vascular Disease.
“We are pleased to be presenting these exciting findings at PVRI [the conference] and are encouraged by the data generated to date, as we believe LIQ861 can help overcome some of the limitations of current nebulized [mist-delivered] therapies,” Neal Fowler, the CEO of Liquidia, said in a press release.
“LIQ861 has the potential to maximize the therapeutic benefits of treprostinil in treating PAH [pulmonary arterial hypertension] by safely and efficiently delivering higher doses of drug deeply into the lungs using a convenient, disposable” dry powder inhaler, Fowler added.
Liquidia’s proprietary PRINT technology improves treprostinil’s delivery to the lungs. The delivery mechanism is a disposable dry powder inhaler.
Treprostinil increases lung function by reducing blood vessel constriction there. It is a synthetic version of prostacyclin, a potent blood-vessel-widening agent that PAH patients have too little of.
The U.S. Food and Drug Administration has approved formulations of treprostinil that are delivered orally, with a mist and intravenously.
“Local delivery of prostacyclin analogs [such as treprostinil] to the lungs is the ideal route of administration, as it minimizes the off-tissue adverse side effects of systemic [body-wide] delivery by delivering the drug where it is needed in the lungs,” said Robert Roscigno, senior vice president of product development at Liquidia.
“The clinical use of inhaled prostacyclin analogs is currently limited to nebulized therapies, which are inherently constrained by specific safety profiles, dosing convenience and efficacy. Prostacyclin analogs are central to PAH therapy, and as such, there exists a strong need to develop products that can maximize their therapeutic benefits,” Roscigno added.
Liquidia is enrolling participants in a Phase 3 trial, which it calls INSPIRE — for Investigation of the Safety and Pharmacology of Dry Powder Inhalation of Treprostinil. About 100 patients with PAH are expected to take part in the study (NCT03399604) at several sites in the United States. They will receive 25 mcg, 50 mcg, 75 mcg and 100 mcg doses of inhaled treprostinil. The company expects to announce the key results in 2019.