FDA Rejects Pitolisant for EDS

“We are disappointed with this short-term setback, but our long-term strategy for pitolisant in IH remains firmly on track with our focus on Pitolisant HD,” said Jeffrey M. Dayno, M.D., President and Chief Executive Officer of Harmony Biosciences. “We made the decision to submit the sNDA based on our belief in pitolisant’s overall benefit-risk profile in IH and our deep commitment to the patient community, despite the challenge associated with this submission. Our long-term business strategy has always been to extend our leadership in sleep/wake through the development of Pitolisant HD, an enhanced and higher-dose formulation, which represents the more significant opportunity in IH given its optimized profile and provisional patent filed out to 2044. We are on track to initiate a Phase III registrational trial of Pitolisant HD in IH in Q4 2025, with a target PDUFA date in 2028.”

“Our planned Phase III registrational trial, a double-blind, randomized, parallel-group study in patients with IH, is based on input from the FDA,” said Kumar Budur, M.D., M.S., Chief Medical and Scientific Officer at Harmony Biosciences. “We believe this study design will effectively demonstrate the benefit of pitolisant in patients with IH based on the robust clinical response that was observed in the Phase III INTUNE Study. We are grateful to the patients and clinicians who participated in the INTUNE Study, and our commitment to these patients remains steadfast. With the initiation of this pivotal Phase III trial in Q4 2025, we will continue to advance pitolisant-based treatments to address their unmet needs.”

Although the primary outcome for EDS between pitolisant and placebo did not reach statistical significance in the randomized withdrawal phase of the Phase III INTUNE Study, the data from the open-label phase showed that patients experienced improvements on the Epworth Sleepiness Scale that were five times greater than what is recognized as clinically meaningful. Furthermore, the majority of patients in the long-term extension study achieved normal levels of wakefulness and sustained this response beyond one year.

Pitolisant is marketed as Wakix in the U.S. for the treatment of EDS or cataplexy in adult patients with narcolepsy, and for the treatment of EDS in pediatric patients 6 years of age and older with narcolepsy. Pitolisant is not currently approved for IH.