Harmony Biosciences is facing more of a nightmare than sweet dreams on the road to securing a new use for its excessive daytime sleepiness (EDS) med Wakix. The FDA promptly shot down the company’s bid for an EDS with idiopathic hypersomnia (IH) indication with a Refusal to File (RTF) letter after a missed phase 3 study.

While Wakix (pitolisant) compared to placebo didn’t meet statistical significance in the randomized withdrawal phase of the company’s phase 3 INTUNE study, Harmony maintains that the data from the open-label portion of the study showed improvements that were “five times greater than what is recognized as clinically meaningful,” the company explained in a press release.

“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,” CEO Jeffrey M. Dayno, M.D., said in a statement.

Despite the setback, Harmony isn’t quite giving up on its IH dreams and notes that its long-term business strategy centers on pitolisant HD, a higher-dose formulation of the original drug that represents the “more significant opportunity” in IH, Dayno added. A phase 3 study of that version is planned for the fourth quarter of 2025 with a target FDA decision date in 2028.

That study was based on input from the FDA and is meant to “effectively demonstrate the benefit of pitolisant in patients with IH based on the robust clinical response that was observed in the Phase 3 INTUNE Study,” the company’s chief medical and scientific officer Kumar Budur, M.D., noted.

Wakix was first approved in 2019 for EDS with narcolepsy, then picked up another nod in 2020 for cataplexy in narcolepsy patients. The company expanded its drug's use to pediatric patients for EDS with narcolepsy last year but received a complete response letter in response to its bid for a pediatric cataplexy approval.

If Wakix did make it to market in the proposed IH indication, Harmony’s sleepiness tablets would again go up against Jazz Pharmaceuticals’ Xywav, the first drug approved for the condition. Jazz has maintained a hold on the sleep disorder market since it first launched its Xyrem, a higher sodium formulation of Xywav, in 2002. Wakix and Xywav already rival each other in Wakix’s other indications, but its key advantage is that it is not listed as a controlled substance. Jazz’ offerings, made up of ‘club drug’ gamma-hydroxybutyrate (GHB), are only available through a restricted program due to potential abuse and misuse. 

Xywav pulled $1.35 billion in 2024 sales, while Harmony collected full-year revenues of $714 million.

Harmony and Wakix caught some heat in 2023 when short seller firm Scorpion Capital stung the company in a scathing report likening the Wakix rollout to Biogen’s Aduhelm debacle. The firm pledged to file a citizen’s petition calling on the FDA to snatch back its green light for Wakix, citing dozens of serious side effect reports it claimed to have obtained through Freedom of Information Act requests from the FDA.

Harmony’s shares sank in the wake of the report, but Mizuho Securities analysts characterized it as “potentially misleading” and “perhaps even sensational,” although some accounts of the drug were in line with the team’s views. At the time, a Harmony spokesperson confirmed to Fierce Pharma that it had seen nothing public regarding a citizens' petition.