Palvella Reports Positive Phase 3 Results for QTORIN Rapamycin in Rare Lymphatic Malformation

Palvella Therapeutics reported positive top-line results from its Phase 3 SELVA study evaluating QTORIN 3.9% rapamycin in hydrogel as a once-daily topical treatment for microcystic lymphatic malformations, a rare, serious, and chronically debilitating genetic disease with no FDA-approved therapies. The study met its primary endpoint, the key secondary endpoint, and four additional secondary endpoints, while being well tolerated in both pediatric and adult patients.

SELVA produced a highly statistically significant improvement on the primary endpoint, the microcystic lymphatic malformation Investigator Global Assessment Scale (mLM-IGA). The company reported a mean improvement of +2.13 on the mLM-IGA at week 24 with a p-value of less than 0.001. At week 24, 95% of participants completing the 24-week efficacy evaluation period improved on the primary endpoint, and 86% were rated as "much improved" (+2) or "very much improved" (+3). Improvement on the mLM-IGA was statistically significant at every post-baseline time point assessed and continued to improve through each visit.

The key secondary endpoint, the blinded mLM-MCSS, also showed highly statistically significant improvement. The endpoint was assessed by independent clinicians using randomized, time-blinded photographs at baseline and week 24 and focused on core signs of disease, including lesion height, leaking/bleeding, and vesicle appearance. Each individual component was statistically significant in a pre-specified analysis. All four additional secondary endpoints—PGIC, Live MCSS, CGIS, and PJS—demonstrated highly statistically significant improvements, spanning both clinician- and patient-reported outcomes. All pre-specified key and four secondary efficacy endpoints achieved statistical significance (all p<0.001).

SELVA was described as a single-arm, baseline-controlled Phase 3 study in patients three years and older, with efficacy evaluated over 24 weeks followed by an extension period. FDA guidance supports single-arm trials in rare diseases with well-understood pathophysiology and a defined disease course. Fifty patients received QTORIN rapamycin, with 49 in the ITT population. The company noted there was one patient aged three to five and said the enrolled population reflected meaningful disease burden, with nearly three-quarters of participants having failed prior procedures or medical therapies.

Retention was described as nearly 90% at week 24, and 98% of week 24 completers elected to enter the extension period. The program received support from an FDA Orphan Products Grant, with two tranches of non-dilutive funding awarded.

QTORIN rapamycin was well tolerated, with 17 participants experiencing treatment-emergent adverse events investigators deemed treatment-related. The most common events cited were application site acne, discoloration, and pruritus. Systemic rapamycin levels remained below two nanograms per mL for all patients across all time points, which the company framed as minimal systemic exposure. There were no drug-related serious adverse events.

Six patients withdrew early after being dosed. Five withdrawals were unrelated to study drug (for example, lifestyle or logistical issues). One participant withdrew after an adverse event deemed possibly related to QTORIN rapamycin; the participant had a history of lymphorrhea and withdrew before day 60 due to lymphorrhea.

Palvella plans an NDA submission in H2 2026 and is pursuing expedited paths (Breakthrough and Fast Track). The company has a multilayered IP position including six granted U.S. patents and orphan exclusivity potential. The potential therapy could serve approximately 30,000 U.S. patients with microcystic lymphatic malformations. The company expects pricing in the range of $100,000–$200,000 per patient per year while targeting approximately 400 centers with a 20–40 rep sales force plus MSLs.