The latest INSPIRE Phase 3 trial data on LIQ861 as a treatment for pulmonary arterial hypertension (PAH) support the submission of a New Drug Application (NDA) with the U.S. Food and Drug Administration.
Liquidia Technologies — LIQ861’s manufacturer — announced that it expects to request a pre-NDA meeting with the FDA early in the fourth quarter, followed by NDA submission in late 2019. This will include additional data from ongoing analyses.
“While we have initiated some additional work … we remain encouraged by our clinical observations and the feedback from investigators and the PAH community,” Neal Fowler, CEO of Liquidia, said in a press release.
“We remain highly enthusiastic about LIQ861 as demonstrated in our INSPIRE trial, and are fully committed to bringing LIQ861 to the PAH community to better the lives of individuals living with PAH,” Fowler said.
LIQ861 is being developed as an alternative to the currently available inhaled treprostinil treatment Tyvaso (marketed by United Therapeutics). It is a palm-sized inhaler that delivers high doses of uniform treprostinil particles, improving deep-lung delivery efficacy, and enhancing its therapeutic benefits.
The open-label Phase 3 INSPIRE trial (NCT03399604) enrolled PAH patients who had started treatment with LIQ861 by transitioning from stable doses of Tyvaso, or who had started LIQ861 treatment as an add-on therapy to no more than two oral non-prostacyclin PAH therapies.
A preliminary analysis showed that doses of LIQ861 ranging between 25 and 150 micrograms were well-tolerated by patients after two months of treatment, with no serious adverse events reported.
In addition, positive trends were observed in both groups concerning their ability to perform physical activities, as well as stabilizing or improving patients’ quality of life.
INSPIRE has also included a crossover sub-study in which 18 PAH patients received single doses of LIQ861 and Tyvaso. This approach allowed a more detailed, direct comparison of both therapies concerning their stability and availability in the body.
The most recent results suggest that 1-2 inhalations of 75 micrograms capsule strength of LIQ861 achieved the same effects as a 54-microgram dose of Tyvaso (nine inhalations), the maximum recommended label dose of this approved therapy.
Still, both LIQ861 and Tyvaso showed some systemic variability, which has been reported in prior studies of treprostinil, and is thought to be caused by variations in disease severity.
“I am very encouraged by the LIQ861 clinical results and believe it could be an important treatment option for PAH patients. Clinical observations, including the Tyvaso transition group having continued on LIQ861 at a high rate, suggest that LIQ861 is being dosed at therapeutic levels,” said Lewis J. Rubin, MD, professor at the University of California San Diego, adjunct professor at Columbia University College of Physicians and Surgeons, and a senior adviser to the LIQ861 program.
Liquidia is still working to better characterize and supplement the information on LIQ861’s overall metabolization within the body.