RARE Daily

Palvella Reports Positive Topline Results from Phase 2 Study in Rare Genetic Skin Disease

March 9, 2023

Rare Daily Staff

Palvella Therapeutics reported topline results from a phase 2 study of Qtorin rapamycin to treat the rare and chronic skin condition microcystic lymphatic malformations.

Microcystic lymphatic malformations is characterized by localized masses of malformed lymphatic vessels that protrude through the skin barrier and persistently leak lymph fluid and bleed, often leading to recurrent serious infections and cellulitis. It is driven by a genetic defect in the PI3K/AKT/mTOR pathway. There are no FDA-approved treatments for the estimated more than 30,000 individuals living with microcystic lymphatic malformations in the United States.

Qtorin rapamycin 3.9 percent is a novel targeted topical therapy being studied for microcystic lymphatic malformations. Palvella is enrolling a phase 2 clinical study for people with microcystic lymphatic malformations.

The proof-of-concept phase 2, multi-center, open-label study featured multiple efficacy assessments, including clinician and patient global impression assessments as well as assessments of individual clinical manifestations that are important disease burdens for individuals living with microcystic lymphatic malformations  (lesion height, leaking, bleeding, erythema, and crusting/hyperkeratosis). A total of 12 individuals with microcystic lymphatic malformations received Qtorin rapamycin once-daily for 12 weeks. Key findings from among the prespecified efficacy endpoints comparing end of treatment to the pre-treatment baseline period demonstrated improvements in several clinician and patient-reported outcomes.

All twelve participants in the study demonstrated improvements on the Patient Global Impression of Change and Crusting/Hyperkeratosis scales with all rated as either “Much Improved” or “Very Much Improved” by the clinicians after 12 weeks of treatment with Qtorin rapamycin. 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.

In the study, Qtorin rapamycin was generally well-tolerated with the most common adverse events being application site pain and pruritus. No participants experienced drug related serious adverse events, and no unexpected adverse events occurred. No rapamycin was detected in the systemic circulation for all participants at all timepoints in the study. Palvella plans to present additional results of the phase 2 study, including the results of the qualitative exit interviews, at an upcoming scientific meeting.

Palvella completed an End of Phase 2 Meeting with the FDA in February 2023. Pending additional interactions with FDA, Palvella anticipates potentially initiating a pivotal phase 3 study of Qtorin rapamycin in the second half of 2023. The FDA has granted Orphan Drug and Fast Track designations to Qtorin rapamycin for the treatment of microcystic lymphatic malformations. The European Medicines Agency (EMA) has also granted Orphan Drug designation to Qtorin rapamycin for the treatment of microcystic LMs.

“People living with microcystic lymphatic malformations s face daily challenges and frequent, sometimes life-threatening hospitalizations due to cellulitis. Current treatments are inadequate, invasive, and do not address the underlying mechanisms of this debilitating disease,” said James Treat, a pediatric dermatologist at Children’s Hospital of Philadelphia and study investigator and consultant to Pavella. “The encouraging results from the phase 2 study of Qtorin rapamycin build upon the large, growing evidence base supporting targeted therapeutic intervention of microcystic lymphatic malformations via the mTOR pathway.”

Photo: James Treat, a pediatric dermatologist at Children’s Hospital of Philadelphia and study investigator and consultant to Pavella




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