Liquidia Technologies has completed the enrollment for the safety part of a Phase 3 trial evaluating the safety and tolerability of LIQ861, an inhaled dry power formulation of treprostinil for the treatment of pulmonary arterial hypertension (PAH).
According to Liquidia, current treatment with inhaled treprostinil in a mist formulation, sold under the brand name Tyvaso by United Therapeutics, is inconvenient for many PAH patients because it requires dozens of breaths a day using a nebulizer that needs daily setup and cleaning.
As a result, the company is developing LIQ861, an inhaled dry powder formulation of treprostinil that can be delivered by a discrete, hand-held inhaler, as a more comfortable and efficient alternative to Tyvaso.
Like the mist formulation of Tyvaso, the dry powder formulation of LIQ861 is expected to maximize the therapeutic effects of treprostinil, allowing local delivery to the lungs, reducing off-tissue side effects, and enabling the safe administration of higher doses.
LIQ861 is being produced using Liquidia’s PRINT Technology (Particle Replication in Nonwetting Templates), a platform that allows the manufacturing of highly uniform particles, with the desired pharmacological properties, on a commercially viable scale.
A prior Phase 1 study in healthy volunteers showed that single administration of LIQ861 was safe and well-tolerated in all the doses tested (ranging between 25 mcg and 150 mcg). At the highest doses (100 mcg and 150 mcg), the therapy remained in the blood for as long as four hours in about half of the participants, suggesting it has the potential to manage symptoms between dosing cycles.
Now, the company is testing LIQ861 in a pivotal, open-label, Phase 3 clinical trial called INSPIRE (NCT03399604), which will determine the safety profile and pharmacological parameters of LIQ861 in PAH patients.
To date, a total of 109 PAH patients have been enrolled across multiple U.S. sites, reaching the established enrollment goal for the safety portion of the trial. Among the participants enrolled, 104 have already received at least two weeks of treatment with LIQ861.
The primary goals of the study are to evaluate the long-term safety and tolerability of LIQ861 in PAH patients transitioning from stable doses of Tyvaso, or who are taking up to two approved non-prostacyclin, oral PAH therapies.
Other objectives are to compare treprostinil bioavailability (the amount of the drug that reaches the blood) and pharmacokinetics (absorption, distribution, metabolism, and elimination by the body) between Tyvaso and LIQ861.
These two pharmacological parameters will be determined in a sub-study with patients transitioning from Tyvaso to LIQ861; patient enrollment for this portion of the trial is still underway.
“We have made significant progress in the second half of 2018 with … the recent completion of enrollment for the safety portion of our pivotal Phase 3 clinical trial, INSPIRE, evaluating LIQ861 for the treatment of pulmonary arterial hypertension. Based on feedback from the U.S. FDA [Food and Drug Administration], we believe that this trial will support the NDA [new drug application] filing for LIQ861, which we are targeting to submit in late 2019,” Neal Fowler, CEO of Liquidia, said in a company press release.
Liquidia expects to announce the two-week safety data of the INSPIRE study in the first quarter of 2019, followed by the pharmacokinetics results later that year.