Topical QTORIN Rapamycin Significantly Reduces Cutaneous VM Bleeding in Phase 2 TOIVA Trial

New findings from the phase 2 TOIVA trial suggest that topical QTORIN rapamycin may improve bleeding and patient-reported outcomes in individuals with cutaneous venous malformations (VMs), a rare vascular disorder.¹ The data were presented in Chicago, Illinois, at the 83rd Annual Meeting of the Society for Investigative Dermatology by Palvella Therapeutics.

Background and Study Design

Cutaneous venous malformations are chronic vascular anomalies that can cause pain, swelling, bleeding, discoloration, and functional impairment. Currently, there are no FDA-approved therapies specifically indicated for these lesions. According to the company, QTORIN rapamycin has the potential to become the first approved treatment for the estimated more than 75,000 individuals in the US living with cutaneous VMs.

The TOIVA study is a phase 2, single-arm, open-label, baseline-controlled trial evaluating once-daily topical QTORIN rapamycin over a 12-week efficacy period followed by a 12-week treatment extension. The trial enrolled patients with cutaneous venous malformations and assessed both clinician-reported and patient-reported outcomes. Previously reported results from December 2025 showed that the study met statistical significance on multiple predefined efficacy endpoints.²

Significant Reductions in Bleeding

Among patients who had bleeding at baseline, all participants demonstrated improvement in bleeding severity by week 12. Investigators used the Cutaneous Venous Malformations Investigator Global Assessment Bleeding scale (cVM-IGA Bleeding), a 7-point clinician-assessed measure ranging from “Very Much Worse” (-3) to “Very Much Improved” (+3). In the subgroup of patients with baseline bleeding (n = 4), the mean improvement was +2.5 points at week 12, which reached statistical significance (p = 0.003).

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At week 12, 100% of these patients were rated as either “Much Improved” or “Very Much Improved” on the bleeding assessment scale. Patient satisfaction findings were similarly positive. All patients with bleeding at baseline reported being either “satisfied” or “very satisfied” with treatment on the overall satisfaction item of the Treatment Satisfaction Questionnaire for Medication at week 12.

“Bleeding is a common and serious problem caused by cutaneous venous malformations. The TOIVA study showed that QTORIN™ rapamycin significantly reduced bleeding and improved the appearance and height of lesions in most patients,” Michael Kelly, MD, PhD, pediatric hematologist and oncologist at the Cleveland Clinic’s Vascular Anomalies Program and Executive Director of the Lymphangiomatosis & Gorham’s Disease Alliance, said in a statement. “Cutaneous venous malformations affect many aspects of a patient’s life, resulting in pain, functional limitations, and mental health issues. TOIVA showed a strong correlation between improvements in clinical measures and patient-reported outcomes, suggesting that QTORIN™ rapamycin could potentially reduce the overall burden of this rare disease.”¹

Qualitative Substudy Results

In addition to the clinical efficacy findings, the presentation highlighted results from a pre-specified qualitative interview substudy designed to better characterize the patient experience. The substudy was conducted in line with the FDA’s Patient-Focused Drug Development framework and aimed to capture symptoms, functional limitations, and treatment goals most meaningful to patients.

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The interviews underscored that the burden of cutaneous VMs extends beyond visible lesion severity as patients described a range of symptoms, including bluish discoloration, swelling, pain or discomfort, protrusions, and bleeding or leakage. They also reported substantial impacts on daily functioning, including limitations in physical activity, work or school participation, and social engagement.

Emotional and psychosocial effects were also prominent themes in the interviews. Patients described distress related to the visibility of lesions, reinforcing the broader quality-of-life burden associated with moderate-to-severe disease. Importantly, the qualitative findings suggested that patient priorities may not always align fully with traditional clinician-assessed severity measures. Improvements in appearance, pain reduction, and decreased lesion size were considered to be major treatment goals.

Next Steps

The company noted that the correlation between clinical improvements and patient-reported satisfaction observed in TOIVA may support the potential role of QTORIN rapamycin in reducing the overall disease burden associated with cutaneous venous malformations. Palvella is also developing QTORIN rapamycin for microcystic lymphatic malformations and clinically significant angiokeratomas, as well as QTORIN pitavastatin for disseminated superficial actinic porokeratosis. Both investigational products remain unapproved by the FDA.

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References

1. Palvella Therapeutics Announces New Data from the Phase 2 TOIVA Trial of QTORIN™ Rapamycin in Cutaneous Venous Malformations Presented at the 83rd Annual Meeting of the Society for Investigative Dermatology. News release. Globe Newswire. Published May 15, 2026. Accessed May 15, 2026. https://www.globenewswire.com/news-release/2026/05/15/3295760/0/en/palvella-therapeutics-announces-new-data-from-the-phase-2-toiva-trial-of-qtorin-rapamycin-in-cutaneous-venous-malformations-presented-at-the-83rd-annual-meeting-of-the-society-for-.html

2. Palvella Therapeutics Announces Positive Topline Results from Phase 2 TOIVA Clinical Trial of QTORIN™ 3.9% Rapamycin Anhydrous Gel (QTORIN™ rapamycin) for the Treatment of Cutaneous Venous Malformations, a Serious, Rare Genetic Disease with No FDA-approved Therapies. News release. Palvella Therapeutics. Published December 15, 2025. Accessed May 15, 2026. https://ir.palvellatx.com/news-releases/news-release-details/palvella-therapeutics-announces-positive-topline-results-phase-0