License pact for L606, potential long-acting version of Tyvaso, expands
Therapy in Phase 3 trial to be marketed by Liquidia and Pharmosa if approved
Liquidia has expanded a license agreement with Pharmosa Biopharm, acquiring rights to market L606, a potential inhaled formulation of treprostinil now in a Phase 3 study, across Europe, Japan, and other regions as well as in North America.
The two-part and open-label Phase 3 clinical trial (NCT04691154), sponsored by Liquidia, is evaluating the safety and tolerability of L606 in adults with pulmonary arterial hypertension (PAH) or pulmonary hypertension associated with interstitial lung disease (PH-ILD) at five sites across the U.S.
Liquidia also obtained rights to use Pharmosa’s next-generation nebulizers to deliver L606. The treatment is a liposomal formulation of treprostinil, a vasodilator that’s the active agent in Tyvaso, an approved inhalation therapy by United Therapeutics to improve exercise ability in adults with PAH or PH-ILD. L606 is designed to be slowly released in a patient’s lungs, so as to be longer acting.
Liposomal formulation means the drug is contained in tiny, fat-like particles, and vasodilators are medications that relax and widen blood vessels to lower blood pressure.
L606 is intended to be given twice daily using a nebulizer
L606, developed by Pharmosa, is a sustained-release formulation of treprostinil, designed to be given twice daily using a hand-held nebulizer similar to ones used with dry-powder treatment formulations. A slower release of the medication intends to extend its period of exposure in the lungs relative to Tyvaso, inhaled by patients four times a day.
“This partnership has the potential to be transformational for people living with PAH and PH-ILD, as it will combine Liquidia’s expertise as a leader in the field of pulmonary hypertension with Pharmosa’s deep experience in inhaled liposomal formulations,” Rajeev Saggar, MD, Liquidia’s chief medical officer, said in a company press release.
In the Phase 3 clinical trial’s first part, adults with PAH or PH-ILD who had been using Tyvaso moved to twice daily treatment with L606. Reasonable safety was seen with L606 doses up to 360 micrograms (mcg) twice daily, researchers stated in a American Thoracic Society 2024 conference presentation, with the most common side effect being cough and others being dyspnea (shortness of breath), dizziness, and blurred vision. That 360 mcg dose is equivalent 25 or more breaths four times per day of Tyvaso, they added.
Its second part involves a separate patient group thought likely to benefit from inhaled treprostinil by study investigators.
The launch of a pivotal study of L606 in PH-ILD patients is possible this year.
“We are delighted by the interest from the global medical and patient communities, many of which lack access to inhaled formulations of treprostinil, as we prepare to initiate the L606 pivotal study in PH-ILD later this year,” Saggar said. “We are also encouraged by the recent scientific advice from the European Medicines Agency that supports our plan to proceed with the study as designed.”
Approved treatments for people with PH-ILD lacking in many countries
In a previous Phase 1 study (NCT04041648) assessing L606’s pharmacokinetics — its movement into, through, and out of the body — in healthy adults, the treatment showed therapeutic levels for up to 12 hours, with a blood plasma peak concentration seven times lower than Tyvaso, the company reported.
Under a 2023 licensing agreement between the two companies, Liquidia is responsible for developing the therapy, handling regulatory requirements, and, if approval is given, marketing it in the U.S. and Canada, while Pharmosa continues to manufacture L606.
“With more than 100,000 PAH and PH-ILD patients in the major countries outside North America, improvements of the treatment strategies in this region are essential since there is no approved treatment for PH-ILD outside the U.S,” said Pei Kan, PhD, Pharmosa’s president.
Pharmosa, which is based in Taiwan, retains right to market the therapy in China, Korea, Taiwan, the Middle East, North Africa, Turkey, and Southeast Asia, should it be approved.
Under the agreement, the company will receive an upfront payment of $3.5 million, with the potential for up to $157.75 million more in milestone payments and royalties for sales outside North America.
A dry powder inhalation formulation of treprostinil by Liquidia, called Yutrepia, was given tentative approval by the U.S. Food and Drug Administration in 2021 to improve exercise ability in adults with PAH, and later extented to PH-ILD. Tentative approval means the therapy has met the regulatory criteria for approval, but in this case, final approval and marketing await the May 2025 expiration of exclusive marketing rights given to United Therapeutics’ Tyvaso DPI.
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