WAYNE, Pa. — (Nasdaq: PVLA) Palvella Therapeutics, Inc. (Palvella or “the Company”), a clinical-stage biopharmaceutical company focused on developing and commercializing novel therapies to treat patients suffering from serious, rare skin diseases for which there are no U.S. Food and Drug Administration (FDA)-approved therapies, today announced positive topline results from the Company’s Phase 2 TOIVA study of QTORIN™ 3.9% rapamycin anhydrous gel (QTORIN™ rapamycin) for the treatment of cutaneous venous malformations (cutaneous VMs).
“Based on the large magnitude of the treatment effect observed in the majority of patients in the Phase 2 TOIVA study, QTORIN™ rapamycin has potential to become first-line therapy and to establish a much-needed standard of care for individuals living with cutaneous venous malformations,” said Megha Tollefson, M.D., pediatric dermatologist at Mayo Clinic and Principal Investigator of the Phase 2 TOIVA study. “Cutaneous venous malformations are congenital, chronic, progressive lesions that persist throughout life and can have a profound impact on patients’ quality of life. They may affect functionally critical areas of the body, often leading to daily discomfort, limitations in activities, and substantial burden for patients and their families. Current procedure-based approaches can be painful, ineffective, or both, and result in high rates of recurrence. Taken together, we believe the Phase 2 data represent a milestone day for individuals living with cutaneous venous malformations, and we look forward to working with Palvella to advance development of this therapy for patients as quickly as possible.”
TOIVA is a Phase 2, single-arm, open-label, baseline-controlled clinical trial of QTORIN™ rapamycin administered topically once daily for a 12-week efficacy evaluation period followed by a 12-week treatment extension period, for cutaneous VMs. The study enrolled 16 participants, ages six and older, at leading vascular anomaly centers across the U.S. Multiple measures of efficacy, including change in clinician and patient global impression assessments, as well as assessments of specific individual clinical manifestations which contribute to disease burden, were evaluated. To help contextualize changes on efficacy endpoints and, specifically, better understand any patient quality of life impact resulting from QTORIN™ rapamycin, qualitative exit interviews were conducted by a third-party interviewer with a subset of participants from the Phase 2 study.
Key findings from among the study’s pre-specified efficacy endpoints at Week 12 demonstrated improvements in both clinician- and patient-reported outcomes:
| Efficacy Endpoints at Week 12 (ITT Population) | Mean Change from Baseline (n=15) | Nominal, Two-sided p-value | |
| Dynamic Change Scales (7-point scales ranging from -3 to +3; positive values indicate improvements from baseline) | |||
| Overall Cutaneous VM Investigator Global Assessment (Overall cVM-IGA) | 1.5 | <0.001 | |
| cVM-IGA Height/Engorgement | 1.3 | <0.001 | |
| cVM-IGA Appearance (visualization/color of affected veins) | 1.5 | <0.001 | |
| cVM-IGA Bleeding | 0.7 | 0.045 | |
| Overall Patient Global Impression of Change (PGI-C) | 1.1 | <0.001 | |
| Static Severity Scales (5-point scales ranging from 1 to 5; negative values indicate improvements from baseline) | |||
| Overall Clinician Global Impression of Severity (CGI-S) | -1.0 | <0.001 | |
| cVM-MCSS (Cutaneous VM Multi-Component Static Scale) Severity of Height/Engorgement | -1.3 | <0.001 | |
| cVM-MCSS Severity of Appearance (visualization/color of affected veins) | -1.1 | <0.001 | |
| Overall Patient Global Impression of Severity (PGI-S) | -0.5 | 0.027 | |
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The Overall Cutaneous Venous Malformations Investigator Global Assessment (Overall cVM-IGA) is a 7-point, clinician-assessed, single-item efficacy endpoint measuring change in severity from baseline, with the numeric rating scale ranging from “Very Much Worse” (-3) to “Very Much Improved” (+3).
On the Overall cVM-IGA at Week 12:
- 73% of trial participants (11/15 participants) improved
- 67% of trial participants (10/15 participants) were either “Much Improved” (+2) or “Very Much Improved” (+3)
- No trial participants (0/15 participants) were “Minimally Worse” (-1), “Much Worse” (-2), or “Very Much Worse” (-3)
Represented in the ten (10) participants who were rated either “Much Improved” (+2) or “Very Much Improved” (+3) on the Overall cVM-IGA at Week 12 were participants with (i) genetically confirmed TEK mutations, (ii) genetically confirmed PIK3CA mutations, and (iii) a non-TEK/PIK3CA mutation or unconfirmed genotype.
Genetic mutation confirmation was not required for entry into the Phase 2 TOIVA study. Additional data from trial participants, including mutation confirmation, continue to be collected, with genotype-stratified results planned for presentation at future medical meetings. Based on analysis of data at Week 12, the Company does not anticipate requiring confirmed genotypes or genetic testing in future studies.
Similar to previous clinical trials of QTORIN™ rapamycin, in the Phase 2 TOIVA study QTORIN™ rapamycin was generally well-tolerated, with the most common treatment-emergent adverse events being application site reactions (erythema, 25%). All treatment-related adverse events were moderate or mild, with no unexpected adverse events reported. Rapamycin levels were below the lower limit of quantification (2 ng/mL) in systemic circulation on a standard lab assay for all participants at all timepoints in the study.
“Based on the strength of the Phase 2 TOIVA results, including the 73% of participants who improved on the Overall cVM-IGA at Week 12, Palvella is planning for near-term discussions with FDA regarding the potential for Breakthrough Therapy Designation and a Phase 3 pivotal study, as well as the newly announced Plausible Mechanism Pathway,” said Wes Kaupinen, Founder and Chief Executive Officer of Palvella. “We are deeply grateful to the patients and families who participated in this trial, as well as the investigators and clinical centers whose partnership made this study possible. These data reinforce our conviction in the therapeutic potential of QTORIN™ rapamycin, the strength of the QTORIN™ platform, and our long-term vision to become the leading rare disease company focused on developing and commercializing novel therapies for patients with serious, rare skin diseases.”
FDA has previously granted Fast Track Designation to QTORIN™ rapamycin for the treatment of venous malformations.
About Cutaneous Venous Malformations
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, 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 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 skin diseases, many of which are lifelong in nature. Palvella’s lead product candidate, QTORIN™ 3.9% rapamycin anhydrous gel (QTORIN™ rapamycin), is currently being developed for the treatment of microcystic lymphatic malformations, cutaneous venous malformations, and clinically significant angiokeratomas. Palvella’s second product candidate, QTORIN™ pitavastatin, is currently being developed for the topical treatment of disseminated superficial actinic porokeratosis. For more information, please visit www.palvellatx.com or follow Palvella on LinkedIn or X (formerly known as Twitter).
QTORIN™ rapamycin and QTORIN™ pitavastatin are for investigational use only and neither has been approved by the FDA or by any other regulatory agency for any indication.
Contact Information
Investors
Wesley H. Kaupinen
Founder and CEO, Palvella Therapeutics
[email protected]
Media
Marcy Nanus
Managing Partner, Trilon Advisors LLC
[email protected]