FDA Rejects Harmony's Wakix Application for Idiopathic Hypersomnia, Company Remains Optimistic

Harmony Biosciences faced a setback in its bid to expand the indications for its sleep-regulating drug Wakix, as the U.S. Food and Drug Administration (FDA) declined to review the company's application for idiopathic hypersomnia. Despite this regulatory hurdle, the pharmaceutical firm remains confident in its long-term strategy and the drug's potential.

FDA Issues Refusal to File Letter

On Wednesday, Harmony Biosciences announced that it had received a Refusal to File (RTF) letter from the FDA regarding its application to add idiopathic hypersomnia to Wakix's label. The FDA issues RTF letters when submissions are deemed incomplete, signaling that the application cannot be reviewed in its current form.

Jeffrey Dayno, CEO of Harmony, characterized the FDA's decision as a "short-term setback" but emphasized that it would not significantly impact the company's broader objectives. "Our long-term strategy for [Wakix] in [idiopathic hypersomnia (IH)] remains firmly on track with our focus on the high-dose (HD) formulation of the drug," Dayno stated.

Focus Shifts to High-Dose Formulation

Harmony's strategic pivot to the high-dose formulation of Wakix appears to be well-received by industry analysts. H.C. Wainwright analysts expressed continued optimism about the company's prospects, noting that the HD formulation represents "the more significant opportunity in IH given its optimized profile."

The company is preparing to initiate a Phase III trial for HD Wakix in narcolepsy during the fourth quarter of 2025. This study will assess narcolepsy-related fatigue, which Harmony considers a novel endpoint in the field.

Financial Outlook and Previous Clinical Data

Despite the regulatory setback, Harmony maintains its 2025 financial outlook, projecting net revenue between $820 million and $860 million for the year. This confidence is partly based on the established success of Wakix in its current indication.

Wakix, an antagonist of the histamine-3 receptor, was first approved by the FDA in 2019 for treating excessive daytime sleepiness in adults with narcolepsy. In October 2023, Harmony released topline data from the Phase III INTUNE study, which showed promising results for Wakix in idiopathic hypersomnia patients. The drug elicited treatment responses in 83% of participants, although it missed its primary endpoint of significantly improving daytime sleepiness over four weeks as measured by the Epworth Sleepiness Scale.