Palvella Therapeutics Announces First Patients Dosed in Phase 2 TOIVA Clinical Trial of QTORIN™ 3.9% Rapamycin Anhydrous Gel (QTORIN™ rapamycin) for the Treatment of Cutaneous Venous Malformations
Palvella Therapeutics has announced that the first patients have been dosed in the Phase 2 TOIVA clinical trial of QTORIN™ 3.9% rapamycin anhydrous gel for treating cutaneous venous malformations (cutaneous VMs). This single-arm, baseline-controlled trial will enroll around 15 subjects across leading vascular anomaly centers in the U.S.
Cutaneous VMs are a serious genetic disease that affects over 75,000 diagnosed patients in the U.S., causing significant morbidity and functional impairment. Currently, there are no FDA-approved therapies for this condition. QTORIN™ rapamycin aims to be the first approved therapy and standard of care in the U.S. for cutaneous VMs.
The study will evaluate the safety and efficacy of QTORIN™ rapamycin, with safety assessed based on adverse events and efficacy measured by changes from baseline to week 12 in clinician and patient global impression assessments. QTORIN™ rapamycin is a topical mTOR inhibitor designed to minimize systemic exposure and adverse reactions.
The FDA granted Fast Track Designation to QTORIN™ rapamycin in April 2024, highlighting its potential to address the unmet medical needs of patients with venous malformations.
Palvella Therapeutics ha annunciato che i primi pazienti sono stati trattati nel trial clinico di Fase 2 TOIVA del gel anidro di rapamicina QTORIN™ 3,9% per il trattamento delle malformazioni venose cutanee (VM cutanee). Questo studio a braccio singolo e controllato per baseline arruolerà circa 15 soggetti nei principali centri per anomalie vascolari negli Stati Uniti.
Le VM cutanee sono una grave malattia genetica che colpisce oltre 75.000 pazienti diagnosticati negli Stati Uniti, causando significativa morbilità e impairment funzionale. Attualmente, non esistono terapie approvate dalla FDA per questa condizione. La rapamicina QTORIN™ punta a essere la prima terapia approvata e standard di cura negli Stati Uniti per le VM cutanee.
Lo studio valuterà la sicurezza e l'efficacia della rapamicina QTORIN™, con la sicurezza valutata in base agli eventi avversi e l'efficacia misurata dai cambiamenti dalla linea di base fino alla settimana 12 nelle valutazioni globali da parte di clinici e pazienti. La rapamicina QTORIN™ è un inibitore topico dell'mTOR progettato per ridurre al minimo l'esposizione sistemica e le reazioni avverse.
Nel aprile 2024, la FDA ha concesso la Designazione di Fast Track alla rapamicina QTORIN™, evidenziando il suo potenziale per affrontare i bisogni medici insoddisfatti dei pazienti con malformazioni venose.
Palvella Therapeutics ha anunciado que los primeros pacientes han sido tratados en el ensayo clínico de Fase 2 TOIVA del gel anhidro de rapamicina QTORIN™ 3,9% para el tratamiento de malformaciones venosas cutáneas (VM cutáneas). Este ensayo de brazo único y controlado por línea base inscribirá alrededor de 15 sujetos en los principales centros de anomalías vasculares en Estados Unidos.
Las VM cutáneas son una grave enfermedad genética que afecta a más de 75.000 pacientes diagnosticados en Estados Unidos, causando una morbilidad significativa y deterioro funcional. Actualmente, no hay terapias aprobadas por la FDA para esta condición. La rapamicina QTORIN™ tiene como objetivo ser la primera terapia aprobada y estándar de atención en Estados Unidos para las VM cutáneas.
El estudio evaluará la seguridad y eficacia de la rapamicina QTORIN™, con la seguridad evaluada en función de los eventos adversos y la eficacia medida por los cambios desde la línea base hasta la semana 12 en las evaluaciones de impresión global de clínicos y pacientes. La rapamicina QTORIN™ es un inhibidor mTOR tópico diseñado para minimizar la exposición sistémica y las reacciones adversas.
En abril de 2024, la FDA otorgó la Designación de Vía Rápida a la rapamicina QTORIN™, destacando su potencial para abordar las necesidades médicas no satisfechas de los pacientes con malformaciones venosas.
팔벨라 테라퓨틱스는 QTORIN™ 3.9% 무수 라파마이신 젤의 피부 정맥 기형 치료를 위한 2상 TOIVA 임상 시험에서 첫 번째 환자가 투약되었다고 발표했습니다. 이 단일군, 기준군 대조 임상 시험은 미국의 주요 혈관 이상 센터에서 약 15명의 피험자를 등록할 예정입니다.
피부 정맥 기형은 미국에서 진단된 75,000명 이상의 환자에게 영향을 미치는 심각한 유전 질환으로, 상당한 이환율과 기능 장애를 초래합니다. 현재 이 질환에 대해 FDA의 승인을 받은 치료법은 없습니다. QTORIN™ 라파마이신은 피부 정맥 기형을 위한 미국 내 최초의 승인 치료제 및 표준 치료법이 되는 것을 목표로 하고 있습니다.
이 연구는 QTORIN™ 라파마이신의 안전성과 유효성을 평가할 것이며, 안전성은 부작용을 기준으로 평가되고 유효성은 임상 의사와 환자의 전반적인 인상 평가에서 기준선부터 12주까지의 변화를 통해 측정됩니다. QTORIN™ 라파마이신은 전신 노출 및 부작용을 최소화하도록 설계된 국소 mTOR 저해제입니다.
FDA는 QTORIN™ 라파마이신에 대해 2024년 4월 신속 심사 지정을 부여하여 정맥 기형 환자들의 충족되지 않은 의료적 필요를 해결할 잠재력을 강조했습니다.
Palvella Therapeutics a annoncé que les premiers patients ont été traités dans l'essai clinique de Phase 2 TOIVA du gel anhydre de rapamycine QTORIN™ 3,9 % pour le traitement des malformations veineuses cutanées (VM cutanées). Cet essai à bras unique, contrôlé en fonction de la ligne de base, recrutera environ 15 sujets dans des centres de référence sur les anomalies vasculaires aux États-Unis.
Les VM cutanées sont une maladie génétique grave qui touche plus de 75 000 patients diagnostiqués aux États-Unis, entraînant une morbidité significative et une altération fonctionnelle. Actuellement, il n'existe aucune thérapie approuvée par la FDA pour cette condition. La rapamycine QTORIN™ vise à être la première thérapie approuvée et le standard de soins aux États-Unis pour les VM cutanées.
L'étude évaluera la sécurité et l'efficacité de la rapamycine QTORIN™, la sécurité étant évaluée sur la base des événements indésirables et l'efficacité mesurée par des changements par rapport à la ligne de base jusqu'à la semaine 12 dans les évaluations globales des cliniciens et des patients. La rapamycine QTORIN™ est un inhibiteur topique de l'mTOR conçu pour minimiser l'exposition systémique et les réactions indésirables.
En avril 2024, la FDA a accordé à la rapamycine QTORIN™ la désignation d'Accélération, mettant en avant son potentiel à répondre aux besoins médicaux non satisfaits des patients souffrant de malformations veineuses.
Palvella Therapeutics hat angekündigt, dass die ersten Patienten im Phase-2-TOIVA-Studie des QTORIN™ 3,9 % anhydritischen Rapamycingels zur Behandlung von kutanen venösen Malformationen (kutane VMs) behandelt wurden. Diese einarmige, baseline-kontrollierte Studie wird etwa 15 Probanden in führenden Zentren für vaskuläre Anomalien in den USA einschreiben.
Kutane VMs sind eine schwerwiegende genetische Erkrankung, die über 75.000 diagnostizierte Patienten in den USA betrifft und erhebliche Morbidität sowie Funktionseinschränkungen verursacht. Derzeit gibt es keine von der FDA zugelassenen Therapien für diese Erkrankung. QTORIN™ Rapamycin zielt darauf ab, die erste zugelassene Therapie und den Standard der Versorgung in den USA für kutane VMs zu werden.
Die Studie wird die Sicherheit und Wirksamkeit von QTORIN™ Rapamycin bewerten, wobei die Sicherheit anhand von Nebenwirkungen und die Wirksamkeit durch Veränderungen von der Basislinie bis zur Woche 12 in den globalen Eindrucksbewertungen von Klinikern und Patienten gemessen wird. QTORIN™ Rapamycin ist ein topischer mTOR-Inhibitor, der entwickelt wurde, um die systemische Exposition und Nebenwirkungen zu minimieren.
Die FDA hat im April 2024 der Rapamycin QTORIN™ die Fast-Track-Designierung erteilt, was ihr Potenzial zur Behebung der unerfüllten medizinischen Bedürfnisse von Patienten mit venösen Malformationen hervorhebt.
- First patients dosed in Phase 2 TOIVA clinical trial for QTORIN™ rapamycin.
- Potential to be the first FDA-approved therapy for cutaneous venous malformations.
- FDA granted Fast Track Designation to QTORIN™ rapamycin in April 2024.
- The trial will only enroll approximately 15 subjects, which may limit the statistical power and generalizability of the results.
- The study's single-arm design lacks a control group, which may affect the robustness of efficacy data.
Insights
The initiation of Phase 2 TOIVA trial for QTORIN™ rapamycin represents a significant milestone in rare disease therapeutics. The trial targets a critical unmet medical need for 75,000+ U.S. patients with cutaneous venous malformations (VMs), who currently lack FDA-approved treatment options.
The study's design is strategically sound - a single-arm, baseline-controlled trial with 15 participants is appropriate for a rare disease proof-of-concept study. The inclusion of both clinician and patient global impression assessments strengthens the trial's potential to demonstrate meaningful clinical benefit. The Fast Track Designation secured in April 2024 could accelerate the regulatory pathway.
Mechanistically, targeting the PI3K/mTOR pathway through topical application is innovative, potentially offering better safety profile than systemic treatments. The 3.9% rapamycin anhydrous gel formulation could provide localized treatment while minimizing systemic exposure - a important advantage over current off-label systemic mTOR inhibitors.
For Palvella Therapeutics (market cap: $162.6M), this trial initiation strengthens their position in the rare disease space. The addressable market of 75,000+ diagnosed patients in the U.S. presents a substantial commercial opportunity, particularly given the lack of FDA-approved alternatives.
The Fast Track Designation enhances the asset's value proposition by potentially reducing time-to-market and development costs. For rare disease therapeutics, first-mover advantage is important - QTORIN™ rapamycin could establish significant market presence before potential competitors emerge.
Having multiple vascular anomaly centers involved in the trial suggests strong clinical community engagement, which could facilitate future commercialization efforts. The focus on both pediatric and adult populations expands the potential market reach and reimbursement opportunities.
Phase 2 single-arm, baseline-controlled trial evaluating QTORIN™
Cutaneous VMs are a serious and lifelong genetic disease that can result in substantial morbidity and functional impairment of the skin affecting an estimated more than 75,000 diagnosed patients in the U.S.
QTORIN™ rapamycin has the potential to be the first approved therapy and standard of care in the U.S. for cutaneous VMs
WAYNE, Pa., Jan. 08, 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 FDA-approved therapies, today announced the first patients have recently been dosed in TOIVA, a multicenter, Phase 2 clinical trial designed to evaluate the safety and efficacy of QTORIN™
“Cutaneous VMs are a serious, lifelong disease which leads to significant disease burden for children and adults living with the disease, including risk of serious complications such as bleeding, ulceration, thrombosis, and pain leading to significant impact on quality of life and daily function,” said Megha M. Tollefson, M.D., Pediatric Dermatologist and Medical Director of Mayo Clinic Vascular Malformation Clinic. “We’re excited to have the first patients dosed in the landmark Phase 2 TOIVA study evaluating QTORIN rapamycin, a targeted topical therapy with potential to inhibit the mammalian target of rapamycin (mTOR) pathway which is a causative driver of this disease. A potential new treatment option would be transformative for children and adults living with this disease, as no FDA-approved therapies currently exist.”
Cutaneous VMs are a rare genetic disease caused by mutations in genes that cause overactivation of the PI3K/mTOR signaling pathway, leading to dysfunctional veins within the skin. These malformations can cause substantial morbidity and functional impairment, significantly impact quality of life, and are associated with severe bleeding, 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.
The Phase 2 TOIVA study is a single-arm, open-label, baseline-controlled clinical trial of QTORIN™ rapamycin administered topically once daily for the treatment of cutaneous VMs. Safety and tolerability will be assessed based on the incidence and severity of adverse events. This proof-of-concept study includes multiple measures of efficacy, including change from baseline to week 12 in clinician and patient global impression assessments as well as assessments of specific individual clinical manifestations which contribute to disease burden. The Phase 2 study is expected to enroll approximately 15 participants, ages six and older, at leading vascular anomaly centers across the U.S.
QTORIN rapamycin is a novel, patented
About Palvella Therapeutics
Founded and led by rare drug disease drug development veterans, Palvella Therapeutics (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.
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, the sufficiency of Palvella’s capital resources; Palvella’s cash runway; statements regarding 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; the expected timing of initiating, as well as the design of Palvella’s Phase 2 clinical trial of QTORIN™ rapamycin in cutaneous venous malformations. 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 “Risk Factors” section of Palvella’s definitive proxy statement/information statement dated November 8, 2024 and other documents filed by Palvella from time to time with the Securities Exchange Commission. 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.
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Contact Information
Investors
Wesley H. Kaupinen
Founder and CEO, Palvella Therapeutics
wes.kaupinen@palvellatx.com
Media
Stephanie Jacobson
Managing Director, Argot Partners
palvella@argotpartners.com
FAQ
What is the objective of the Phase 2 TOIVA clinical trial for PVLA?
How many patients will be enrolled in the PVLA Phase 2 clinical trial?
What is QTORIN™ rapamycin designed to treat?
What kind of study design is used in the PVLA Phase 2 TOIVA trial?
When did the FDA grant Fast Track Designation to QTORIN™ rapamycin?
What are the primary measures of efficacy in the PVLA trial?
What is the significance of QTORIN™ rapamycin for patients with cutaneous venous malformations?
