Liquida’s LIQ861 Found to Improve Exercise Capacity, Quality of Life in PAH

LIQ861, Liquidia Technologies’ proprietary inhaled dry powder formulation of the vasodilator treprostinil, improves exercise capacity and quality of life for people with pulmonary arterial hypertension (PAH), according to data from the Phase 3 INSPIRE trial.

Treatment with LIQ861 also led to improvements in other exploratory endpoints assessed in INSPIRE (NCT03399604). This formulation reduced the severity of symptoms associated with heart failure and increased the proportion of patients meeting two or three PAH low-risk criteria since the start of the trial, the data showed.

The study findings were presented by the company Aug. 5 at a prerecorded virtual presentation during the American Thoracic Society (ATS) Annual Meeting, which took place online. Registrants can access the platform until November 10.

“We are very pleased with the results of LIQ861 on these exploratory endpoints and believe these findings warrant further evaluation in this difficult to treat patient population,” Nicholas Hill, MD, principal investigator of INSPIRE, and chief of the pulmonary, critical care and sleep division, and professor of medicine at Tufts University School of Medicine, said in a press release.

LIQ861 is a dry powder formulation of treprostinil, a vasodilator that widens blood vessels in the lungs, lowering blood pressure. It is based on Liquidia’s PRINT technology, which enables the production of highly uniform drug particles with controlled size, shape, and chemical properties.

The experimental therapy is specifically optimized for deep-lung delivery in patients, when inhaled through a user-friendly, small, portable, dry powder inhaler.

The safety, tolerability, and pharmacological properties of LIQ861 are currently being investigated in the Phase 3 INSPIRE trial. The study enrolled 121 people with PAH, including a group of patients who were on a stable regimen of non-prostacyclin therapies and received LIQ861 as an add-on treatment. A second group switched from Tyvaso — an inhaled formulation of treprostinil marketed by United Therapeutics — to LIQ861.

For those who transitioned from United’s therapy, the initial dose of LIQ861 was based on the dose of Tyvaso they were receiving before switching treatments. For those receiving LIQ861 as an add-on therapy, the initial dose given was 26.5 micrograms (mcg), four times daily. Dose increments of LIQ861 were allowed in both groups of patients at the discretion of physicians, depending on the participants’ symptoms.

Earlier data from the 113 patients who completed the first two months of treatment showed LIQ861 was safe and well-tolerated, with no serious adverse events found related to the treatment. 

Now, Liquidia presented data from several exploratory endpoints assessed during the trial. The data were analyzed to evaluate the effects of LIQ861 on patients’ quality of life, exercise capacity, heart failure severity, and PAH severity.

The findings showed that two months of treatment with LIQ861 improved patients’ exercise capacity — reflected by a median increase of 10.1 meters in the six-minute walk distance (6MWD) test — and quality of life, as assessed by the Minnesota Living With Heart Failure Questionnaire.

Treatment with LIQ861 also reduced the severity of symptoms associated with heart failure, based on New York Heart Association functional class (NYHA FC) status, in 20.5% of the patients. That improvement was maintained in 75.9% of the patients. The percentage of participants meeting two or three PAH low-risk criteria since the start of the study also increased.

During the first two months of the study, more than 70% of the participants were able to increase their LIQ861 dosage to 79.5 mcg or more.

According to Liquidia, in the group of patients who transitioned from Tyvaso to LIQ861, most preferred using the dry-powder inhaler of LIQ861 over Tyvaso’s Inhalation System.

“Previously reported primary endpoints from the INSPIRE study support the safety and tolerability profile of LIQ861 and a continuation of positive trends seen in these exploratory endpoints will only reinforce its potential as a viable treatment option, if approved, for patients with PAH,” Hill said.

INSPIRE was one of the three clinical trials whose findings supported the new drug application (NDA) Liquidia submitted to the U.S. Food and Drug Administration requesting the approval of LIQ861 for the treatment of PAH. The U.S. agency accepted to review the company’s NDA in April, and is set to make a decision on its approval by Nov. 24.

“If approved, we believe that the LIQ861 dry powder inhaler could offer PAH patients a much-needed alternative treatment option and we are deeply committed to delivering such options to the PAH community,” said Tushar Shah, MD, chief medical officer of Liquidia.