Palvella Therapeutics Advances QTORIN™ Rapamycin for Rare Genetic Skin Diseases
Key Insights
Palvella Therapeutics (search)' QTORIN™ rapamycin (search) shows promise in treating microcystic lymphatic malformations (search) (LMs), with Phase 2 results published in the Journal of Vascular Anomalies.
The Phase 2 study of QTORIN™ rapamycin (search) demonstrated significant improvements in microcystic LMs, leading to the expansion of the Phase 3 SELVA trial to include children aged 3-5.
QTORIN™ rapamycin (search) is also under evaluation in a Phase 2 trial (TOIVA) for cutaneous venous malformations (search), with first patients dosed, addressing a significant unmet need.
Palvella Therapeutics (search) is making strides in the development of QTORIN™ rapamycin (search), a novel topical formulation of sirolimus, for the treatment of rare genetic skin diseases. The company's lead product candidate is being evaluated in Phase 3 and Phase 2 clinical trials targeting microcystic lymphatic malformations (search) (LMs) and cutaneous venous malformations (search) (VMs), respectively.
Positive Phase 2 Results for Microcystic LMs
Palvella Therapeutics (search) recently announced the publication of positive results from its Phase 2 study of QTORIN™ 3.9% rapamycin anhydrous gel for the treatment of microcystic LMs in the Journal of Vascular Anomalies (JoVA). The study demonstrated that 100% of participants experienced either "Much Improved" or "Very Much Improved" ratings based on the Clinician Global Impression of Change following 12 weeks of treatment with QTORIN™ rapamycin (search).
The Phase 2 study (n=12) assessed the change from pre-treatment baseline to the end of treatment (Week 12) with once-daily topical QTORIN™ rapamycin (search). The results showed nominal statistical significance across several efficacy endpoints, including clinician and patient global impression assessments, as well as assessments of individual clinical manifestations that are important disease burdens for individuals living with microcystic LMs. The treatment was generally well-tolerated, with no participants experiencing drug-related serious adverse events.
Expansion of Phase 3 SELVA Trial
Building on these promising results, Palvella is expanding its Phase 3 SELVA clinical trial to include younger patients. The SELVA trial, which is evaluating QTORIN™ 3.9% rapamycin anhydrous gel for the treatment of microcystic LMs, will now include patients ages 3 to 5 years old. Previously, trial participants were required to be at least 6 years old. This decision follows communication with the U.S. Food and Drug Administration (FDA), in which the agency deemed the company's proposed expansion acceptable.
Joyce Teng MD, PhD, Professor of Dermatology and Pediatrics at Stanford University and Principal Investigator of the SELVA Study, stated, “Early intervention is essential to minimize disease burden during children’s development which is why I am so excited by the opportunity QTORIN rapamycin presents to the younger pediatric population.”
Palvella is currently enrolling approximately 40 patients in SELVA, a 24-week, Phase 3, single-arm, baseline-controlled trial of QTORIN™ rapamycin (search) for the treatment of microcystic LMs. Topline data from the study is expected in Q1 2026. The FDA has granted Breakthrough Therapy Designation, Fast Track Designation, and Orphan Drug Designation to QTORIN™ rapamycin for the treatment of microcystic LMs. Additionally, the SELVA study is supported by an Orphan Products Grant of up to $2.6 million from FDA’s Office of Orphan Products Development.
Phase 2 TOIVA Trial for Cutaneous Venous Malformations
Palvella Therapeutics (search) has also announced that the first patients have been dosed in TOIVA, a multicenter, Phase 2 clinical trial designed to evaluate the safety and efficacy of QTORIN™ 3.9% rapamycin anhydrous gel (QTORIN™ rapamycin (search)) for the treatment of cutaneous venous malformations (search) (cutaneous VMs).
“Cutaneous VMs are a serious, lifelong disease which leads to significant disease burden for children and adults living with the disease, including risk of serious complications such as bleeding, ulceration, thrombosis, and pain leading to significant impact on quality of life and daily function,” said Megha M. Tollefson, M.D., Pediatric Dermatologist and Medical Director of Mayo Clinic Vascular Malformation Clinic. “We’re excited to have the first patients dosed in the landmark Phase 2 TOIVA study evaluating QTORIN rapamycin, a targeted topical therapy with potential to inhibit the mammalian target of rapamycin (mTOR (search)) pathway which is a causative driver of this disease. A potential new treatment option would be transformative for children and adults living with this disease, as no FDA-approved therapies currently exist.”
The Phase 2 TOIVA study is a single-arm, open-label, baseline-controlled clinical trial of QTORIN™ rapamycin (search) administered topically once daily for the treatment of cutaneous VMs. The study is expected to enroll approximately 15 participants, ages six and older, at leading vascular anomaly centers across the U.S. QTORIN™ rapamycin has the potential to be the first approved therapy and standard of care in the U.S. for cutaneous VMs.
About Microcystic LMs and Cutaneous VMs
Microcystic LMs are a rare, chronically debilitating genetic disease caused by dysregulation of the phosphatidylinositol 3-kinase (PI3K)/mammalian target of rapamycin (mTOR (search)) 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. There are currently no FDA-approved treatments for the estimated more than 30,000 diagnosed patients with microcystic LMs in the United States.
Cutaneous VMs are a rare genetic disease caused by mutations in genes that cause overactivation of the PI3K/mTOR (search) signaling pathway, leading to dysfunctional veins within the skin. These malformations can cause substantial morbidity and functional impairment, significantly impact quality of life, and are associated with severe bleeding, ulceration, thrombosis, and other potential complications. An urgent need exists for an FDA-approved, targeted, localized therapy to treat cutaneous VMs. There are an estimated more than 75,000 diagnosed patients with cutaneous VMs in the U.S.
With no FDA-approved therapies currently available for either microcystic LMs or cutaneous VMs, QTORIN™ rapamycin (search) represents a promising potential treatment option for these rare and debilitating conditions.