Palvella Therapeutics Announces First Patient Dosed in Phase 3 Clinical Trial for Microcystic Lymphatic Malformations Treatment

Palvella Therapeutics, Inc. recently announced the first patient has been dosed in SELVA, a multicenter, Phase 3 clinical trial designed to evaluate the safety and efficacy of QTORIN 3.9% rapamycin anhydrous gel (QTORIN rapamycin) for the treatment of microcystic lymphatic malformations (microcystic LMs).

“Microcystic LMs result from genetic changes that lead to hyperactivation of the causative PI3K/mTOR pathway resulting in malformed lymphatic networks that protrude through the skin.  This results in persistent external lymph fluid drainage, as well as secondary infections and cellulitis that may require urgent medical attention and hospitalization,” said Joyce M. Teng, MD, PhD, Professor of Dermatology and Pediatrics at Stanford University School of Medicine and SELVA Principal Investigator. “Because this serious disease is present at birth and progresses over time without regression, it can result in significant morbidity beginning in childhood and have a lifelong impact.”

SELVA is a Phase 3, single-arm, baseline-controlled clinical trial of QTORIN™ rapamycin administered topically once daily for the treatment of microcystic LMs. The primary efficacy endpoint in SELVA is the change from baseline in the overall microcystic LM Investigator Global Assessment (mLM-IGA) at week 24. The Phase 3 study is expected to enroll approximately 40 participants, ages six and older, at leading vascular anomaly centers across the US. The FDA has granted Breakthrough Therapy Designation, Fast Track Designation, and Orphan Drug Designation to QTORIN rapamycin for the treatment of microcystic LMs. Additionally, Palvella was awarded up to $2.6 million from the FDA’s Office of Orphan Products Development to support the SELVA study.

“We are pleased to have dosed the first patient in our Phase 3 SELVA trial, an important milestone towards our objective of advancing QTORIN rapamycin to potential regulatory approvals and U.S. commercialization,” said Wes Kaupinen, Founder and Chief Executive Officer of Palvella. “QTORIN rapamycin has the potential to be the first approved therapy and standard of care in the U.S. for the estimated more than 30,000 diagnosed patients suffering from microcystic LMs in the US.”

QTORIN rapamycin is the lead product candidate from Palvella’s QTORIN platform. QTORIN rapamycin is a novel, patented 3.9% rapamycin anhydrous gel which aims to harness the potential therapeutic benefits of rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, while minimizing systemic exposure of rapamycin and potential adverse reactions associated with systemic therapy. QTORIN rapamycin is currently under development for the treatment of microcystic LMs, cutaneous venous malformations, and other serious, functionally debilitating skin diseases driven by the overactivation of the mTOR pathway.

Microcystic LMs is a rare, chronically debilitating genetic disease caused by dysregulation of the phosphatidylinositol 3-kinase (PI3K)/mTOR pathway. The disease is characterized by malformed lymphatic vessels that protrude through the skin and persistently leak lymph fluid (lymphorrhea) and bleed, often leading to recurrent serious infections and cellulitis that can cause hospitalization. The natural history of microcystic LMs are persistent and progressive without spontaneous resolution, with symptoms generally worsening during life, including increases in the number and size of malformed vessels that lead to complications and lifetime morbidity. There are currently no FDA-approved treatments for the estimated more than 30,000 diagnosed patients with microcystic LMs in the US.

Founded and led by rare drug disease drug development veterans, Palvella Therapeutics is a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapies to treat patients suffering from serious, rare genetic skin diseases for which there are no FDA-approved therapies. Palvella is developing a broad pipeline of product candidates based on its patented QTORIN platform, with an initial focus on serious, rare genetic skin diseases, many of which are lifelong in nature. Palvella’s lead product candidate, QTORIN 3.9% rapamycin anhydrous gel (QTORIN rapamycin), is currently in clinical development for microcystic lymphatic malformations (microcystic LMs) and cutaneous venous malformations.

In July 2024, Palvella and Pieris Pharmaceuticals, Inc. (Nasdaq: PIRS) announced they have entered into a definitive merger agreement to combine the companies in an all-stock transaction.