# SELVA: A Multicenter, Phase 3 Baseline-Controlled Study Evaluating the Safety and Efficacy of PTX-022 in the Treatment of Microcystic Lymphatic Malformations

> **NIH FDA R01** · PALVELLA THERAPEUTICS, INC. · 2024 · $479,560

## Abstract

FOA Number: RFA-FD-23-001
FOA Title: Clinical Studies of Orphan Products Addressing Unmet Needs of Rare Diseases (R01) Clinical Trials
Required
Proposal Title: SELVA: A Multicenter, Phase 3 Baseline-Controlled Study Evaluating the Safety and Efficacy of PTX-
022 in the Treatment of Microcystic Lymphatic Malformations
Institute: FDA Office of Orphan Products Development
Study Section: N/A
Summary
The objective of this project is to demonstrate the safety and efficacy of PTX-022 (sirolimus) Topical Gel 3.9% w/w for
patients suffering from microcystic lymphatic malformations (microcystic LM). Microcystic LM is a serious, rare, and
chronic disease of the lymphatic system characterized by lymphorrhea, acute cellulitis and significant patient morbidity.
Microcystic LM is an orphan disease with no FDA approved therapies and there is an urgent need to develop the first
FDA approved therapy to treat this debilitating disease.
Microcystic LM is usually present at birth or shortly after, with the pathology often originating in the dermis and
protruding out through the epidermis and stratum corneum. Recent studies have identified that patients with microcystic
LM have postzygotic mutations in PI3K leading to abnormal and increased activation in mTOR signaling as well as its
downstream target vascular endothelial growth factor (VEGF). Oral sirolimus, an mTOR inhibitor which is also known as
rapamycin, has demonstrated preliminary benefit in patients with microcystic LM but its use is limited by the adverse
event profile, requirement for frequent blood monitoring, and limited distribution to the skin. Therefore, Palvella
Therapeutics, Inc. (Palvella) is developing PTX-022, a 3.9% topical sirolimus gel designed to deliver high levels of
sirolimus directly to the site of disease, the epidermis and dermis, while avoiding the systemic side effects of oral
sirolimus. PTX-022 recently completed a Phase 2, 12 patient, open-label clinical study (NCT05050149). Efficacy data
from the Phase 2 study demonstrated statistically significant and clinically meaningful improvements with patients treated
with PTX-022. All twelve patients who entered the study were either “much improved” (n=7, 58%) or “very much
improved” (n=5, 42%) on the clinician global impression of change (CGI-C) and all twelve patients improved on the
patient global impression of change (PGI-C).
Based on the Phase 2 data, FDA awarded PTX-022 Breakthrough Therapy Designation for the treatment of microcystic
LM. Breakthrough Therapy Designation is intended to expedite the development and review of therapies for serious or
life-threatening conditions and whose preliminary clinical evidence indicates that the drug may demonstrate substantial
improvement on one or more clinically significant endpoints over existing therapies. Following a collaborative Type B
Meeting with FDA in April 2024, Palvella is advancing the development of PTX-022 into a registrational Phase 3 study in
patients with microcystic LM. Primar...

## Key facts

- **NIH application ID:** 11104574
- **Project number:** 1R01FD008196-01A1
- **Recipient organization:** PALVELLA THERAPEUTICS, INC.
- **Principal Investigator:** Jeff Martini
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** FDA
- **Fiscal year:** 2024
- **Award amount:** $479,560
- **Award type:** 1
- **Project period:** 2024-09-20 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11104574

## Citation

> US National Institutes of Health, RePORTER application 11104574, SELVA: A Multicenter, Phase 3 Baseline-Controlled Study Evaluating the Safety and Efficacy of PTX-022 in the Treatment of Microcystic Lymphatic Malformations (1R01FD008196-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/11104574. Licensed CC0.

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