Palvella Therapeutics (PVLA) Study Result summary

Study design and patient population

• Phase II TOIVA was a single-arm, baseline-controlled trial evaluating topical QTORIN rapamycin in patients aged six and older with cutaneous venous malformations, a rare genetic disease with no FDA-approved therapies.

• Sixteen participants were enrolled at leading U.S. academic and vascular anomaly centers, with 15 evaluable at 12 weeks.

• Efficacy was assessed using both clinician- and patient-reported outcomes, including global impression and specific clinical manifestations.

• Eligibility was confirmed by independent review, focusing on moderate to severe cutaneous disease; no genetic confirmation was required, reflecting real-world practice.

• Genetic testing was not required, but participants included those with TEK, PIK3CA, and other mutations.

Efficacy results

• QTORIN rapamycin showed highly statistically significant improvements on multiple clinician- and patient-reported efficacy endpoints at 12 weeks.

• 73% of participants (11/15) improved at least one point on the CVM-IGA at Week 12; 67% were rated as much or very much improved.

• Mean effect size on the cVM-IGA clinician scale was +1.5 (p<0.001), with rapid, time-dependent response observed.

• Statistically significant improvements were observed in lesion height, appearance, bleeding, and static severity scales.

• Improvements were consistent across genetic subgroups, including TEK and PIK3CA mutations, and no participants worsened on the CVM-IGA scale at Week 12.

Safety and tolerability

• QTORIN rapamycin was generally well tolerated, with most adverse events being mild or moderate application site reactions (erythema in 25%).

• No severe, unexpected, or drug-related serious adverse events were reported.

• Systemic rapamycin levels remained below quantifiable limits in all participants, minimizing risk of immunosuppression.

• Only one patient was lost to follow-up; 15 of 16 completed the 12-week assessment.