RESEARCH TRIANGLE PARK – One month after a favorable ruling in a patent dispute, Morrisville-based Liquidia has gained tentative approval from the U.S. Food and Drug Administration for Yutrepia, its inhalation powder for treating pulmonary arterial hypertension (PAH).

Tentative approval means that Yutrepia, a formulation of treprostinil, a pulmonary and systemic vasodilator, has met all regulatory standards for quality, safety and efficacy required for approval in the United States.

“The tentative approval for Yutrepia is another step toward providing an important option for patients with PAH in the U.S.,” said Dr. Tushar Shah, chief medical officer of Liquidia. “We believe Yutrepia can improve the limitations of current nebulized therapies by allowing the administration of an expanded dose range of inhaled treprostinil using a proven, convenient, palm-sized device.”

However, due to an ongoing patent dispute with United Therapeutics, Yutrepia can’t yet be marketed in the United States under a regulatory stay pursuant to the Drug Price Competition and Patent Term Restoration Act (Hatch-Waxman Act).

In June 2020, United Therapeutics filed a lawsuit against Liquidia for alleged infringement of three patents related to Tyvaso, its own treprostinil medication for PAH and pulmonary hypertension associated with interstitial lung disease (PH-ILD).

As a result, the FDA can’t give final approval of Yutrepia until the expiration of the regulatory stay on Oct. 27, 2022, or earlier resolution or settlement of the ongoing litigation.
In October, the U.S. Patent Trial and Appeal Board ruled in Liquidia’s favor in a proceeding involving a Tyvaso patent owned by United Therapeutics. In its ruling, the board found that seven of the nine claims were unpatentable. Only two narrower dependent claims remain unresolved.

Damian deGoa, president and chief executive officer of Liquidia, said at the time that the decision was “a clear win” for his company and that he remained confident Liquidia would ultimately prevail on all patent claims asserted against it.

Large market in play

The stakes are high in the treprostinil battle because the addressable market for the inhaled drug is large and expected to grow. In 2020, United Therapeutics reported that Tyvaso, its FDA-approved nebulized formulation of treprostinil for PAH, achieved sales of more than $480 million.

A report in August by Grand View Research estimated the global PAH market would reach $7.7 billion by 2028, expanding at a 4.9 percent compound annual growth rate during the period. The number of PAH cases is rising by 100,000 to 200,000 per year, largely due to risk factors such as alcohol and tobacco consumption, HIV, sedentary lifestyle, smoking and diseases of unknown causes.

In October, however, the FDA declined to approve United Therapeutics’ New Drug Application for Tyvaso DPI, citing an open-inspection issue at a third-party facility that performs analytical testing of treprostinil. United Therapeutics has developed its own next-generation, dry-powder formulation of treprostinil, called Tyvaso DPI, for treating PAH and PH-ILD. Tyvaso DPI, as with Liquidia’s Yutrepia, would be inhaled using a puff-style device rather than a traditional nebulizer, giving patients more convenience.

Company executives said at the time they were confident that the deficiency would be resolved quickly and that Tyvaso DPI could receive approval by the summer of 2022 or earlier.

“Tyvaso DPI will be a groundbreaking advancement for PAH and PH-ILD patients, and we look forward to launching this product no later than the summer of 2022,” said Michael Benkowitz, president and chief operating officer of United Therapeutics. “We reaffirm the achievability of our near-term goal of doubling the number of patients on Tyvaso by the end of 2022, and our longer-term goal of having 25,000 patients on our products by the end of 2025.”

Rare diseases make breathing difficult

PAH is a rare, chronic, progressive disease caused by hardening and narrowing of the pulmonary arteries that can lead to heart failure and eventually death. An estimated 30,000 patients in the United States have the condition.

PH-ILD is also a rare disease of high blood pressure in the lungs caused by other progressive lung diseases.

Treprostinil works by relaxing and widening the blood vessels in the lungs and other parts of the body so that blood can flow more easily.

Yutrepia is indicated for the treatment of PAH to improve exercise ability in adult patients with New York Heart Association Functional Class II-III symptoms. It is a dry powder formulation intended to enhance deep-lung delivery and achieve higher dose levels of treprostinil than current inhaled therapies.
deGoa said the FDA’s tentative approval of Yutrepia was a significant milestone for Liquidia.

“Not only does the tentative approval establish the safety and efficacy of Yutrepia for PAH patients but, in the process, we have validated our proprietary PRINT technology to engineer discrete drug particles with uniform composition, size and shape,” he said. “There is more work to be done. We will now focus our efforts on pre-commercial launch activities and the growing market opportunity for Yutrepia in PAH and potential new indications.”

Liquidia, a publicly held company that was spun out of the University of North Carolina at Chapel Hill in 2004, is focused on the development and commercialization of products in pulmonary hypertension and other applications of its PRINT technology. The company operates through its two wholly owned subsidiaries, Liquidia Technologies and Liquidia PAH.

United Therapeutics, a publicly held company, is focused on finding cures for pulmonary arterial hypertension and other life-threatening diseases. It is headquartered in Silver Spring, Md., and has a research and manufacturing facility in Research Triangle Park that employs more than 400 people.

(C) N.C. Biotech Center