Palvella Therapeutics Announces Scientific Publication in Lymphatic Research and Biology Highlighting Recent Advances in the Pathogenesis of Venous Malformations and the Real-World Use of Rapamycin as an Emerging Targeted Therapy
Palvella Therapeutics (NASDAQ:PVLA) announced the publication of significant research in Lymphatic Research and Biology regarding venous malformations (VMs) and rapamycin treatment. The systematic review, analyzing 26 studies with 98 patients, reinforces the scientific basis for Palvella's QTORIN™ 3.9% rapamycin anhydrous gel.
The research highlights the PI3K/AKT/mTOR pathway as a key driver of VM disease progression and documents the effectiveness of rapamycin in treating VMs. The company's Phase 2 TOIVA trial, which enrolled 16 patients, is evaluating QTORIN™ rapamycin for cutaneous VMs, with top-line data expected in mid-December 2025. The treatment received FDA Fast Track Designation in April 2024, targeting an estimated 75,000+ diagnosed patients in the U.S. who currently lack FDA-approved therapies.
Palvella Therapeutics (NASDAQ:PVLA) ha anunciato la pubblicazione di ricerche significative in Lymphatic Research and Biology riguardanti le malformazioni venose (VM) e il trattamento con rapamicina. La revisione sistematica, che analizza 26 studi con 98 pazienti, rafforza la base scientifica per il gel anidro di rapamicina al 3,9% QTORIN™ di Palvella.
La ricerca mette in evidenza la via PI3K/AKT/mTOR come un fattore chiave nella progressione della malattia VM e documenta l'efficacia della rapamicina nel trattamento delle VM. Il trial di fase 2 TOIVA, che ha arruolato 16 pazienti, sta valutando la rapamicina QTORIN™ per VM cutanee, con i dati principali attesi a metà dicembre 2025. Il trattamento ha ricevuto la Designazione Fast Track FDA nell'aprile 2024, mirata a oltre 75.000+ pazienti diagnosticati negli Stati Uniti che attualmente non dispongono di terapie approvate dalla FDA.
Palvella Therapeutics (NASDAQ:PVLA) anunció la publicación de investigaciones significativas en Lymphatic Research and Biology sobre malformaciones venosas (VM) y el tratamiento con rapamicina. La revisión sistemática, que analiza 26 estudios con 98 pacientes, refuerza la base científica del gel anhidro de rapamicina al 3,9% QTORIN™ de Palvella.
La investigación destaca la vía PI3K/AKT/mTOR como motor clave de la progresión de la VM y documenta la eficacia de la rapamicina en el tratamiento de las VM. El ensayo de fase 2 TOIVA, que incluyó 16 pacientes, está evaluando la rapamicina QTORIN™ para VM cutáneas, con datos principales esperados en diciembre de 2025. El tratamiento recibió la Designación Fast Track de la FDA en abril de 2024, dirigida a más de 75,000 pacientes diagnosticados en Estados Unidos que actualmente no disponen de terapias aprobadas por la FDA.
Palvella Therapeutics (NASDAQ:PVLA)는 정맥 기형(VM) 및 라파마이신 치료에 관한 Lymphatic Research and Biology의 중요한 연구 발표를 발표했습니다. 체계적 고찰은 98명의 환자를 포함한 26개 연구를 분석하며 Palvella의 3.9% 무수 라파마이신 겔(QTORIN™)의 과학적 기초를 강화합니다.
연구는 VM 질환 진행의 핵심 동인으로 PI3K/AKT/mTOR 경로를 강조하고 VM 치료에서 라파마이신의 효과를 입증합니다. 피부 VM를 대상으로 한 Palvella의 2상 TOIVA 임상은 16명의 환자를 등록했으며, 2025년 12월 중순에 주요 데이터를 기대하고 있습니다. 이 치료는 2024년 4월 FDA의 Fast Track 지정을 받았으며, FDA 승인 치료가 현재 없는 미국에서 75,000명 이상 진단 환자를 대상으로 한다고 알려져 있습니다.
Palvella Therapeutics (NASDAQ:PVLA) a annoncé la publication de recherches significatives dans Lymphatic Research and Biology concernant les malformations veineuses (VM) et le traitement par rapamycine. La revue systématique, analysant 26 études avec 98 patients, renforce la base scientifique du gel anhydre QTORIN™ à la rapamycine 3,9% de Palvella.
La recherche met en évidence la voie PI3K/AKT/mTOR comme moteur clé de la progression de la maladie VM et documente l’efficacité de la rapamycine dans le traitement des VM. Le essai de phase 2 TOIVA, qui a recruté 16 patients, évalue la rapamycine QTORIN™ pour les VM cutanées, avec des données préliminaires attendues à mi-décembre 2025. Le traitement a reçu la désignation FDA Fast Track en avril 2024, visant plus de 75 000 patients diagnostiqués aux États-Unis qui n’ont actuellement pas de thérapies approuvées par la FDA.
Palvella Therapeutics (NASDAQ:PVLA) gab die Veröffentlichung bedeutender Forschungen in Lymphatic Research and Biology zu veneralen Malformationen (VM) und Rapamycin-Behandlung bekannt. Die systematische Übersichtsarbeit, die 26 Studien mit 98 Patienten analysiert, stärkt die wissenschaftliche Grundlage für Palvellas QTORIN™ Rapamycin-Anhydrous-Gel mit 3,9%.
Die Forschung hebt den PI3K/AKT/mTOR-Weg als Schlüsselfaktor für das Fortschreiten der VM-Krankheit hervor und dokumentiert die Wirksamkeit von Rapamycin bei der Behandlung von VM. Die Phase-2-TOIVA-Studie des Unternehmens, an der 16 Patienten beteiligt waren, bewertet QTORIN™ Rapamycin für kutane VM, mit Top-Line-Daten, die voraussichtlich Mitte Dezember 2025 erwartet werden. Die Behandlung erhielt im April 2024 die FDA Fast Track Designation und richtet sich an schätzungsweise 75.000+ diagnostizierte Patienten in den USA, die derzeit keine von der FDA genehmigten Therapien haben.
Palvella Therapeutics (NASDAQ:PVLA) أعلن عن نشر أبحاث هامة في Lymphatic Research and Biology تتعلق بتشوّهات وريدية (VMs) وعلاج Rapamycin. المراجعة المنهجية، التي تحلل 26 دراسة و98 مريضاً، تعزز الأساس العلمي لـ QTORIN™ جل Rapamycin الأنهدري بتركيز 3.9%.
تُبرز الأبحاث مسار PI3K/AKT/mTOR كمحرك رئيسي لتقدم مرض VM وتوثّق فَعالية Rapamycin في علاج VM. تجربة المرحلة الثانية TOIVA، التي جُمع فيها 16 مريضاً، تقيم Rapamycin QTORIN™ ل VM الجلدية، مع توقع بيانات رئيسية في منتصف ديسمبر 2025. حصل العلاج على تخصيص FDA Fast Track في أبريل 2024، مستهدفاً أكثر من 75,000 مريض مُشخَّص في الولايات المتحدة لا توجد حالياً علاجات معتمدة من FDA.
Palvella Therapeutics (NASDAQ:PVLA) 宣布在《淋巴研究与生物学》（Lymphatic Research and Biology）发表关于静脉畸形（VM）及雷帕霉素治疗的重大研究。系统性综述分析了26项研究、98名患者，强化了Palvella的3.9%无水雷帕霉素凝胶QTORIN™的科学基础。
研究强调了PI3K/AKT/mTOR途径是VM疾病进展的关键驱动因素，并记录了雷帕霉素在治疗VM中的有效性。公司阶段2的TOIVA试验已招募16名患者，正在评估用于皮肤VM的QTORIN™雷帕霉素，预计在2025年12月中旬公布初步数据。该治疗在2024年4月获得FDA快速通道（Fast Track）指定，目标是在美国约75,000名以上诊断患者中提供尚无FDA批准治疗选项的患者。
- FDA Fast Track Designation received for QTORIN™ rapamycin in April 2024
- Large addressable market with 75,000+ diagnosed VM patients in the U.S.
- Successful completion of Phase 2 TOIVA trial enrollment with 16 patients
- Strong scientific validation through systematic review of 26 studies showing rapamycin efficacy
- No current FDA-approved therapies for cutaneous venous malformations
- Phase 2 trial results still pending, creating uncertainty about treatment efficacy
Insights
Palvella's publication strengthens scientific rationale for QTORIN rapamycin as first potential FDA-approved therapy for venous malformations.
Palvella Therapeutics has published important clinical evidence supporting its lead candidate QTORIN™ 3.9% rapamycin anhydrous gel for cutaneous venous malformations (VMs) - a serious condition affecting over 75,000 diagnosed patients in the US with no FDA-approved treatments.
The publication in Lymphatic Research and Biology includes a systematic review of 26 studies demonstrating the efficacy of rapamycin (sirolimus) in treating VMs. This substantiates Palvella's therapeutic approach targeting the PI3K/AKT/mTOR pathway, which has been identified as a key driver of VM disease proliferation.
Three critical elements make this development particularly significant:
- The Fast Track Designation granted by the FDA in April 2024 acknowledges both the serious unmet medical need and the potential of QTORIN™ rapamycin to address it
- The fully enrolled Phase 2 TOIVA trial with topline results expected in mid-December 2025 represents a near-term catalyst
- The targeted topical delivery approach potentially offers efficacy while minimizing systemic side effects associated with oral rapamycin
The co-authors include respected clinicians from Stanford University, Cleveland Clinic, and Mayo Clinic, adding significant credibility to the scientific basis of Palvella's approach. The publication demonstrates that rapamycin showed efficacy in patients who had inadequate responses to conventional treatments like surgery, sclerotherapy, and laser therapy.
This development positions Palvella to potentially address a significant treatment gap for a condition that causes physical impairment and psychological distress, providing a strong foundation for the upcoming Phase 2 results.
Recent advances in understanding venous malformation disease pathogenesis highlight the PI3K/AKT/mTOR pathway as a key driver of disease proliferation, spurring real-world off-label use of systemic rapamycin (sirolimus)
Publication includes a systematic review of 26 studies evaluating the use of rapamycin for the treatment of venous malformations
Study authors highlight unmet clinical need for venous malformations and lack of FDA-approved pharmacologic options while advocating for an FDA-approved targeted topical formulation of rapamycin for patients with cutaneous venous malformations
WAYNE, Pa., Sept. 17, 2025 (GLOBE NEWSWIRE) -- (Nasdaq: PVLA) Palvella Therapeutics, Inc. (Palvella), a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapies to treat patients suffering from serious, rare genetic skin diseases for which there are no U.S. Food and Drug Administration (FDA)-approved therapies, today announced the publication of a manuscript in Lymphatic Research and Biology which summarizes a systematic literature review of rapamycin for the treatment of venous malformations (VMs). The manuscript supports the scientific rationale and clinical potential of Palvella’s QTORIN™
"This publication highlights the significant unmet need in the management of cutaneous venous malformations and the large, growing real-world experience that rapamycin as a therapy can benefit patients with this challenging disease," said Joyce Teng, M.D., Ph.D., Professor of Dermatology and Pediatrics at Stanford University. "Data summarized in this review further strengthen the scientific and clinical rationale for a targeted, non-systemic approach to treat cutaneous venous malformations which currently have no FDA-approved therapy."
Lymphatic Research and Biology is a peer-reviewed journal dedicated to delivering the most current advances and developments in the genetics, biology, pathology, and diseases and disorders of the lymphatic system. The publication, titled "Sirolimus for Venous Malformations: A Systematic Review of Efficacy and Safety," reviews 26 studies comprising 98 patients treated with rapamycin (also known as sirolimus) for VMs. In addition to Dr. Teng, leading clinicians in the field of vascular malformations, including Michael Kelly, M.D., Ph.D., pediatric hematologist and oncologist at Cleveland Clinic, and Megha Tollefson, M.D., pediatric dermatologist at Mayo Clinic, contributed to the publication. Key findings from the publication included:
- Recent advances in the pathogenesis of VMs have implicated abnormal activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, a critical intercellular pathway that plays a central role in venous malformation expansion and proliferation.
- Interventional treatments, including surgery, sclerotherapy, and laser therapy, are highlighted as potentially inadequate for VMs patients with extensive, cutaneous, or invasive disease.
- The majority of patients showed evidence of treatment efficacy with off-label rapamycin, despite an inadequate response to previous standard treatment; improvements were noted in several areas, including bleeding, functional capacity, quality-of-life measurements, and other clinical signs.
- Across the studies, there was no difference in efficacy based on mutation subtype, although not all studies reported on mutation subtype.
- A targeted, topical formulation of rapamycin could provide clinical benefit for cutaneous VMs by achieving therapeutic levels in the dermis while minimizing the risk of off-target effects of oral rapamycin.
"There is a serious unmet need in cutaneous VMs, with no FDA-approved therapies and a high burden of disease leading to physical and functional impairment and psychological distress," said Jeff Martini, Ph.D., Chief Scientific Officer of Palvella. "This systematic review supports a potentially important role for rapamycin in venous malformations, and further validates Palvella’s approach to potentially address cutaneous venous malformations with QTORIN™ rapamycin, our innovative
Palvella recently announced the completion of enrollment of the Phase 2 TOIVA trial with 16 patients enrolling in the study. The program is focused on evaluating QTORIN™ rapamycin for the treatment of cutaneous VMs, a disease for which there are currently no FDA-approved therapies for the estimated more than 75,000 diagnosed patients in the U.S. In April 2024, the FDA granted Fast Track Designation to QTORIN™ rapamycin for the treatment of VMs.
About Cutaneous Venous Malformations
Cutaneous VMs is a serious, rare genetic disease caused by mutations in genes that cause overactivation of the PI3K/mTOR signaling pathway, leading to dysregulated growth of malformed veins within the skin. These malformations can cause substantial morbidity and functional impairment, significantly impact quality of life, and are associated with bleeding, swelling, ulceration, thrombosis, and other potential complications. An urgent need exists for an FDA-approved, targeted, localized therapy to treat cutaneous VMs. While published case studies and real-world evidence have provided preliminary evidence of clinical benefit from the off-label use of systemic mTOR inhibitors for venous malformations, there are currently no FDA-approved therapies for the estimated more than 75,000 diagnosed patients with cutaneous VMs in the U.S.
About Palvella Therapeutics
Founded and led by rare disease drug development veterans, Palvella Therapeutics, Inc. (Nasdaq: PVLA) is a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapies to treat patients suffering from serious, rare genetic skin diseases for which there are no FDA-approved therapies. Palvella is developing a broad pipeline of product candidates based on its patented QTORIN™ platform, with an initial focus on serious, rare genetic skin diseases, many of which are lifelong in nature. Palvella’s lead product candidate, QTORIN™
QTORIN™ rapamycin is for investigational use only and has not been approved or cleared by the FDA or by any other regulatory agency for any indication.
Forward-Looking Statements
This press release contains forward-looking statements (including within the meaning of Section 21E of the Securities Exchange Act of 1934, as amended, and Section 27A of the Securities Act of 1933, as amended (Securities Act)). These statements may discuss goals, intentions, and expectations as to future plans, trends, events, results of operations or financial condition, or otherwise, based on current beliefs of the management of Palvella, as well as assumptions made by, and information currently available to, the management of Palvella. Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions, and include words such as “may,” “will,” “should,” “would,” “expect,” “anticipate,” “plan,” “likely,” “believe,” “estimate,” “project,” “intend,” and other similar expressions or the negative or plural of these words, or other similar expressions that are predictions or indicate future events or prospects, although not all forward-looking statements contain these words. Statements that are not historical facts are forward-looking statements. Forward-looking statements include, but are not limited to, statements regarding the expected timing of the presentation of data from ongoing clinical trials, Palvella’s clinical development plans and related anticipated development milestones, Palvella’s cash and financial resources and expected cash runway, and the potential of, and expectations regarding, Palvella’s programs, including QTORIN™ rapamycin, and its research-stage opportunities, including its expected therapeutic potential and market opportunity. Forward-looking statements are based on current beliefs and assumptions that are subject to risks and uncertainties and are not guarantees of future performance. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors, including, without limitation: the ability to raise additional capital to finance operations; the ability to advance product candidates through preclinical and clinical development; the ability to obtain regulatory approval for, and ultimately commercialize, Palvella’s product candidates, including QTORIN™ rapamycin; the outcome of early clinical trials for Palvella’s product candidates, including the ability of those trials to satisfy relevant governmental or regulatory requirements; the fact that data and results from clinical studies may not necessarily be indicative of future results; Palvella’s limited experience in designing clinical trials and lack of experience in conducting clinical trials; the ability to identify and pivot to other programs, product candidates, or indications that may be more profitable or successful than Palvella’s current product candidates; the substantial competition Palvella faces in discovering, developing, or commercializing products; the negative impacts of global events on operations, including ongoing and planned clinical trials and ongoing and planned preclinical studies; the ability to attract, hire, and retain skilled executive officers and employees; the ability of Palvella to protect its intellectual property and proprietary technologies; reliance on third parties, contract manufacturers, and contract research organizations; and the risks and uncertainties described in the filings made by Palvella with the Securities and Exchange Commission (SEC), including the annual report on Form 10-K, quarterly reports on Form 10-Q and current reports on Form 8-K, filed with or furnished to the SEC and available at www.sec.gov. The events and circumstances reflected in our forward-looking statements may not be achieved or occur, and actual results could differ materially from those projected in the forward-looking statements. New risk factors and uncertainties may emerge from time to time, and it is not possible for management to predict all risk factors and uncertainties that Palvella may face. Except as required by applicable law, Palvella does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. This press release contains hyperlinks to information that is not deemed to be incorporated by reference into this press release.
Contact Information
Investors
Wesley H. Kaupinen
Founder and CEO, Palvella Therapeutics
wes.kaupinen@palvellatx.com
Media
Marcy Nanus
Managing Partner, Trilon Advisors LLC
mnanus@trilonadvisors.com
FAQ
What are the key findings of Palvella Therapeutics' (PVLA) scientific publication about venous malformations?
When will Palvella Therapeutics (PVLA) release Phase 2 TOIVA trial results?
How many patients are affected by venous malformations in the US that Palvella Therapeutics (PVLA) is targeting?
What is QTORIN rapamycin's current regulatory status for treating venous malformations?
How many patients are enrolled in Palvella Therapeutics' (PVLA) Phase 2 TOIVA trial?
