Lymphatic Research and Biology Journal Publishes Article on Venous Malformations and the Real-Life Application of Rapamycin as a Potential New Therapy, Courtesy of Palvella Therapeutics
In a significant development for patients with Cutaneous Venous Malformations, a rare genetic skin disease with no FDA-approved treatments, Palvella Therapeutics, Inc. is making strides in the development of a targeted, topical formulation of rapamycin. This innovative treatment approach aims to provide clinical benefits by achieving therapeutic levels in the dermis, minimizing off-target effects associated with oral rapamycin.
Palvella Therapeutics, a clinical-stage biopharmaceutical company led by rare disease drug development veterans, is focusing on developing and commercializing therapies for Cutaneous Venous Malformations. The company's broad pipeline of product candidates is based on its patented QTORINTM platform, with an initial focus on serious, rare genetic skin diseases.
Recent advances in the pathogenesis of venous malformations have implicated abnormal activation of the PI3K/AKT/mTOR pathway as a key driver of disease proliferation. The company's topical rapamycin, currently being evaluated in the Phase 2 TOIVA clinical trial, targets this pathway.
The Phase 2 TOIVA trial, which has completed enrollment with 16 patients, is assessing QTORINTM rapamycin for the treatment of Cutaneous Venous Malformations. Top-line data from the trial is anticipated in mid-December 2025. In addition to the TOIVA trial, QTORINTM rapamycin is also being evaluated in the Phase 3 SELVA clinical trial in microcystic lymphatic malformations.
Published research supports the scientific rationale and clinical potential of Palvella's QTORINTM 3.9% rapamycin anhydrous gel (QTORINTM rapamycin) for the treatment of Cutaneous Venous Malformations. A manuscript, published in Lymphatic Research and Biology, is a systematic review of 26 studies evaluating the use of rapamycin for the treatment of venous malformations. The publication underscores the clinical potential of Palvella's topical rapamycin.
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 Venous Malformations in the U.S. Interventional treatments, such as surgery, sclerotherapy, and laser therapy, may be inadequate for patients with extensive, cutaneous, or invasive venous malformations.
The majority of patients showed evidence of treatment efficacy with off-label rapamycin, despite an inadequate response to previous standard treatment. Improvements were noted in several areas, including bleeding, functional capacity, quality-of-life measurements, and other clinical signs.
In April 2024, the FDA granted Fast Track Designation to QTORINTM rapamycin for the treatment of Venous Malformations, underscoring the urgent need for an FDA-approved, targeted, localized therapy to treat Cutaneous Venous Malformations. Palvella Therapeutics' focus on developing and commercializing therapies for rare genetic skin diseases, specifically Cutaneous Venous Malformations, is a promising step towards addressing this unmet medical need.
