Palvella Therapeutics (NASDAQ:PVLA) said it reported positive top-line results from its phase III SELVA study evaluating QTORIN 3.9% rapamycin in hydrogel as a once-daily topical treatment for microcystic lymphatic malformations (mLM), a rare, serious, and chronically debilitating genetic disease with no FDA-approved therapies.
Management highlighted that QTORIN rapamycin met the study’s primary endpoint, the key secondary endpoint, and four additional secondary endpoints, while being “well tolerated” in both pediatric and adult patients. The company also emphasized a high rollover rate into an open-label extension, which executives and the trial’s investigators characterized as supportive of treatment acceptability and perceived benefit.
SELVA efficacy results and endpoint performance
At week 24, Palvella said 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). Dr. Jeff Martini, Palvella’s Chief Scientific Officer, added that 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 company said. 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. Palvella reported that each individual component was statistically significant in a pre-specified analysis.
Palvella also said all four additional secondary endpoints—PGIC, Live MCSS, CGIS, and PJS—demonstrated highly statistically significant improvements, spanning both clinician- and patient-reported outcomes.
Study design, patient population, and retention
SELVA was described as a single-arm, baseline-controlled phase III study in patients three years and older, with efficacy evaluated over 24 weeks followed by an extension period. Palvella said 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 Palvella reported that 98% of week 24 completers elected to enter the extension period.
Management also noted the program received support from an FDA Orphan Products Grant, with two tranches of non-dilutive funding awarded.
Safety, systemic exposure, and discontinuations
Palvella said 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. The company also reported that systemic rapamycin levels remained below two nanograms per mL for all patients across all time points, which it framed as minimal systemic exposure.
Six patients withdrew early after being dosed. Palvella said 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 company said the participant had a history of lymphorrhea and withdrew before day 60 due to lymphorrhea.
Clinical context and case examples
Dr. Michael Kelly of the Cleveland Clinic, an investigator in SELVA, discussed how many patients entering the trial had prior treatment failures, which he said can negatively influence expectations and response. He reviewed several patient examples and described visible improvements after 24 weeks, including reductions in vesicle number and height, lesion flattening, and more normal skin appearance. He read a patient quote describing decreased redness and texture and stating the lesion had become “basically almost flat.”
In response to analyst questions, Dr. Kelly said he would place QTORIN rapamycin as a first-line option for most patients with clinically significant skin involvement, citing efficacy, once-daily at-home administration, and tolerability. He also noted that some patients with deeper lesions may require systemic therapy in addition to topical treatment.
Regulatory timeline, IP strategy, and commercialization plans
Chief Executive Officer Wes Kaupinen said Palvella’s NDA team is assembled and regulatory interactions are underway, with an NDA submission planned for the second half of 2026. He said the company intends to pursue submission under multiple expedited FDA programs, including Breakthrough Therapy and Fast Track designations, which he said have already been granted to QTORIN rapamycin.
In the Q&A, management discussed intellectual property and exclusivity, describing a “multilayered” strategy including patents, manufacturing and formulation trade secrets, and regulatory exclusivity. The company said it has six granted U.S. patents with broad claims across anhydrous formulations of rapamycin and other mTOR inhibitors and method of use, and noted that orphan designation in mLM could provide seven years of exclusivity.
On commercialization, Palvella said it has recruited leadership including Ashley Kline as Chief Commercial Officer and Vimal Patel as Head of Medical Affairs. The company cited epidemiology work indicating over 30,000 diagnosed U.S. patients and estimated about 1,500 new patients per year. Kaupinen said Palvella plans to price the drug in a range of $100,000 to $200,000 per patient per year, with additional pricing testing planned now that phase III data are available. He also said claims work suggests roughly 50% of mLM patients are concentrated in about 400 centers, which the company plans to target, and outlined an expectation of a 20–40 representative orphan sales force supplemented by medical science liaisons.
Kaupinen also discussed broader pipeline plans, including efforts to prioritize additional mTOR-driven skin disease indications and an intention to announce a fourth indication for QTORIN rapamycin in the second half of the year, along with a third product candidate from the QTORIN platform.
About Palvella Therapeutics (NASDAQ:PVLA)
Palvella Therapeutics, Inc (NASDAQ: PVLA) is a clinical‐stage biopharmaceutical company devoted to the discovery and development of innovative therapies for immunological and inflammatory diseases. The company employs a proprietary small‐molecule and biologics platform to identify and modulate key molecular pathways that drive neutrophil‐ and complement‐mediated inflammation, aiming to deliver targeted treatment options for patients with significant unmet medical needs.
Palvella’s pipeline comprises several preclinical assets designed to address both prevalent chronic inflammatory conditions and rare autoinflammatory syndromes.
