FDA Grants Tentative Approval for Liquidia’s Yutrepia (treprostinil) Inhalation Powder

 In continuation of my update on treprostinil

 

Liquidia Corporation  announced that, the U.S. Food and Drug Administration (FDA) has granted tentative approval for Yutrepia™ (treprostinil) inhalation powder, previously referred to as LIQ861. Yutrepia is indicated for the treatment of pulmonary arterial hypertension (PAH) to improve exercise ability in adult patients with New York Heart Association (NYHA) Functional Class II-III symptoms. Tentative approval indicates that Yutrepia has met all regulatory standards for quality, safety and efficacy required for approval in the United States.

 

Dr. Tushar Shah, Chief Medical Officer of Liquidia, said: “We would like to take the opportunity to thank the patients and investigators who participated in the clinical development of Yutrepia. The tentative approval for Yutrepia is another step toward providing an important option for patients with PAH in the U.S. 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.”

The addressable market for inhaled treprostinil is significant and expected to grow. In 2020, United Therapeutics reported that its nebulized formulation of treprostinil indicated for PAH achieved sales of more than $480 million. The attributes of Yutrepia including ease-of-use, convenience, direct lung delivery, and higher dosage range may not only make Yutrepia a preference to nebulized therapy, but also an alternative to oral treatments, and possibly a treatment option to delay the use of parenteral therapies in PAH. There may also be future expansion opportunities for inhaled treprostinil into additional indications.

Damian deGoa, Chief Executive Officer of Liquidia added: “This is a significant milestone for Liquidia. We are really proud of our team. 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. 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.”

Due to a regulatory stay pursuant to the Drug Price Competition and Patent Term Restoration Act (Hatch-Waxman Act), Yutrepia cannot yet be marketed in the United States. In June 2020, United Therapeutics filed a lawsuit against Liquidia for alleged infringement of three patents related to Tyvaso®. As a result, the FDA cannot give final approval of Yutrepia until the expiration of the regulatory stay on October 27, 2022, or earlier resolution or settlement of the ongoing litigation.

About Yutrepia™(treprostinil) inhalation powder
Yutrepia is an investigational, inhaled dry powder formulation of treprostinil delivered through a proven, convenient, palm-sized device. On November 5, 2021, the FDA issued a tentative approval for Yutrepia, which is indicated for the treatment of pulmonary arterial hypertension (PAH) to improve exercise ability in adult patients with New York Heart Association (NYHA) Functional Class II-III symptoms. Yutrepia was designed using Liquidia’s PRINT® technology, which enables the development of drug particles that are precise and uniform in size, shape, and composition, and that are engineered for optimal deposition in the lung following oral inhalation. Liquidia has completed INSPIRE, or Investigation of the Safety and Pharmacology of Dry Powder Inhalation of Treprostinil, an open-label, multi-center phase 3 clinical study of Yutrepia in patients diagnosed with PAH who are naïve to inhaled treprostinil or who are transitioning from Tyvaso (nebulized treprostinil). Yutrepia was previously referred to as LIQ861 in investigational studies.

Liquidia Corporation Provides Update on New Drug Application for Yutrepia (treprostinil) inhalation powder

Liquidia Corporation (the Company) (NASDAQ: LQDA) announced  the U.S. Food and Drug Administration (FDA) providing  an update on its review of the New Drug Application (NDA) for Yutrepia™ (treprostinil) inhalation powder to treat pulmonary arterial hypertension (PAH) and pulmonary hypertension associated with interstitial lung disease (PH-ILD). The FDA informed the Company that it is confirming the process for adding the PH-ILD indication as an amendment to the NDA for Yutrepia. Accordingly, the FDA is not able to issue an action letter in time to meet the previously issued Prescription Drug User Fee Act (PDUFA) goal date of January 24, 2024, and their review remains ongoing. The FDA did not request any additional clinical data to support the NDA and did not issue a new PDUFA goal date.

Dr. Roger Jeffs, Chief Executive Officer, said: “We are in active communication with the FDA regarding the process we followed to amend our NDA to add PH-ILD to the labeled indication. Whether the NDA is amended or supplemented, we will continue to prepare for the final FDA approval of Yutrepia to treat both PAH and PH-ILD patients following the expiration of regulatory exclusivity for Tyvaso® on March 31, 2024. As communicated by the tentative approval to treat PAH, Yutrepia has already met the regulatory standards for quality, safety and efficacy. We remain committed to addressing the unmet needs across all patients whose lives may be improved by the unique benefits of Yutrepia.”

On November 5, 2021, the FDA issued a tentative approval for Yutrepia for the treatment of PAH to improve exercise ability in adult patients with New York Heart Association (NYHA) Functional Class II-III symptoms. In July 2023, Liquidia filed an amendment to its New Drug Application for Yutrepia, seeking to add PH-ILD to the label. The FDA previously confirmed that Yutrepia may include the treatment of PH-ILD to the proposed label for Yutrepia without additional clinical studies.

Yutrepia also remains subject to ongoing litigation. Liquidia filed a request for Judge Andrews of the U.S. District Court for the District of Delaware (District Court) to set aside the injunction that was instituted in August 2022 tied to litigation filed by United Therapeutics (UTHR) alleging patent infringement of U.S. Patent No. 10,716,793 (the ‘793 Patent) in Case No. 1:20-cv-00755-RGA (the Original Hatch-Waxman Litigation). On December 20, 2023, the United States Court of Appeals for the Federal Circuit (CAFC) affirmed the earlier decision by the Patent Trial and Appeal Board (PTAB), which found all claims of the ‘793 Patent to be unpatentable due to the existence of prior art cited by Liquidia in inter partes review proceedings.

Additionally, in September 2023, UTHR filed a second complaint for patent infringement in District Court in Case No. 1:23-cv-00975-RGA (the New Hatch-Waxman Litigation). As of January 22, 2024, the only patent at issue is U.S. Patent No. 11,826,327 (the ‘327 Patent) which issued November 30, 2023. UTHR has stipulated to the dismissal of the ‘793 Patent from the New Hatch-Waxman Litigation as a result of the CAFC decision affirming invalidity of the '793 Patent. The ’327 Patent, the sole remaining patent at issue in the New Hatch-Waxman Litigation, was not issued before Liquidia submitted the NDA for Yutrepia in January 2020 to treat PAH. Therefore, the Company believes that final FDA approval for Yutrepia will not be subject to any statutory 30-month stay arising from the New Hatch-Waxman Litigation per Section 505(c)(3)(C) of the Federal Food, Drug and Cosmetic Act.

Ref: https://en.wikipedia.org/wiki/Treprostinil

Read https://www.drugs.com/nda/yutrepia_240125.html

Liquidia Corporation Provides Update on New Drug Application for Yutrepia (treprostinil) inhalation powder

Treprostinil as IV infusion reduces breathlessness in PAH patients...

The treatment, continuous intravenous (IV) treprostinil, (see structure, the drug has already been approved by the U.S. Food and Drug Administration for the treatment of pulmonary arterial hypertension PAH) based on its similarity to an approved treatment delivered subcutaneously (directly into the skin). Practicing physicians, had hesitated to endorse the treatment because it did not have its own placebo-controlled study. But now the researchers from University of Rochester Medical Center, have come up with interesting results.

The more interesting part of their research is that PAH patients had higher than normal blood levels of factors known to play central roles in the clogging of arteries as part of major diseases like atherosclerosis and hypertension, including angiopoietin-2 (Ang-2) and platelet derived growth factor. Treatment with treprostinil was associated with lowers levels of Ang-2.

Though the mode of action has to be established (relaxing muscles surrounding blood vessels for easier blood flow and turning off sticky ingredients that cause blood clots e.g. platelets) , its is a good achievement. Treprostinil-treated patients feel like they are breathing easier because their lung arteries, not the lungs themselves, are working more efficiently. Better understanding of the mechanisms involved may lead to refinements in drug design; for example, blocking the effects of Ang-2 to treat the disease (may be easier on patients than a continuous IV infusion). Though further studies are essential, its a good achievement and hope in the days to come people with PHT will definitely breathe a sigh of relief instead of breathlessnessssss.....

Source : http://www.urmc.rochester.edu/news/story/index.cfm?id=2711

United Therapeutics Announces FDA Approval of the Implantable System for Remodulin

In continuation of my update on treprostinil

United Therapeutics Corporation,  announced approval by the U.S. Food and Drug Administration (FDA) of a New Drug Application (NDA) for the use of Remodulin (treprostinil) Injection in the Implantable System for Remodulin® (ISR).

The ISR has been developed under a collaboration with Medtronic (NYSE: MDT). In December 2017, Medtronic received FDA approval of a premarket application (PMA) for a proprietary intravascular infusion catheter to be used with its SynchroMed™ II implantable infusion pump and related infusion system components (together referred to as the Implantable System for Remodulin) in order to deliver Remodulin for the treatment of pulmonary arterial hypertension (PAH).

"We are extremely excited to offer this new option to patients suffering from PAH," said Martine Rothblatt, Ph.D., Chairman and Chief Executive Officer of United Therapeutics. "During the course of the DelIVery study, we received considerable physician and patient interest in the ISR. We are grateful to our collaborators at Medtronic for reaching this milestone and look forward to continuing our collaboration."

Remodulin was originally approved by the FDA to treat PAH by continuous subcutaneous and intravenous routes of administration in 2002 and 2004, respectively, using external pumps. In the case of intravenous users, the therapy can be very burdensome and brings a risk of sepsis due to the use of a central indwelling catheter.

The ISR provides patients a new option for delivery of intravenous Remodulin, where the entire delivery system is implanted into the body and will be refilled by healthcare professionals at intervals of up to 16 weeks depending on the patient's dose, using a syringe needle through the patient's skin.

"External infusion pumps have been used to deliver prostacyclins for PAH, but managing the therapy places a significant burden on patients, interferes with their daily activities, and runs a high risk of infections," said David Steinhaus, M.D., general manager of the Heart Failure business, part of the Cardiac and Vascular Group at Medtronic. "This fully implantable drug delivery system was designed to address these serious patient care concerns."

United Therapeutics funded and Medtronic conducted the DelIVery for PAH clinical trial, which was a safety study of a new implantable catheter designed for intravascular drug (Remodulin) delivery with the SynchroMed™ II implantable infusion pump. In 2013, the study met its primary objective of demonstrating a rate of catheter-related complications below 2.5 per 1,000 patient-days while using the fully implantable system (p < 0.0001).

https://www.drugs.com/newdrugs/united-therapeutics-announces-fda-approval-implantable-remodulin-4790.html