Palvella Therapeutics Announces First Patients Dosed in Phase 2 Trial of QTORIN 3.9% Rapamycin Anhydrous Gel for the Treatment of Cutaneous Venous Malformations

Palvella Therapeutics, Inc. recently announced the first patients have recently 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) for the treatment of cutaneous venous malformations (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, MD, 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) 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.”

Cutaneous VMs are a rare genetic disease caused by mutations in genes that cause overactivation of the PI3K/mTOR 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. While published case studies and real-world evidence have provided preliminary evidence of clinical benefit from the off-label use of systemic mTOR inhibitors for venous malformations, there are currently no FDA-approved therapies for the estimated more than 75,000 diagnosed patients with cutaneous VMs in the US.

The Phase 2 TOIVA study is a single-arm, open-label, baseline-controlled clinical trial of QTORIN rapamycin administered topically once daily for the treatment of cutaneous VMs. Safety and tolerability will be assessed based on the incidence and severity of adverse events. This proof-of-concept study includes multiple measures of efficacy, including change from baseline to week 12 in clinician and patient global impression assessments as well as assessments of specific individual clinical manifestations which contribute to disease burden. The Phase 2 study is expected to enroll approximately 15 participants, ages six and older, at leading vascular anomaly centers across the US.

QTORIN rapamycin is a novel, patented 3.9% rapamycin anhydrous gel which aims to harness the potential therapeutic benefits of rapamycin, an mTOR inhibitor, while minimizing systemic exposure of rapamycin and potential adverse reactions associated with systemic therapy. In April 2024, the FDA granted Fast Track Designation to QTORIN rapamycin for the treatment of venous malformations.

Founded and led by rare drug disease drug development veterans, Palvella Therapeutics (Nasdaq: PVLA) 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 being evaluated in the Phase 3 SELVA clinical trial in microcystic lymphatic malformations and the Phase 2 TOIVA clinical trial in cutaneous venous malformations. For more information, visit www.palvellatx.com.