Request to FDA to File and Priority Review the sNDA for Pitolisant

We, people living with idiopathic hypersomnia, central disorders of hypersomnolence, and the broader rare sleep disorder advocacy community, request that the FDA (1) file, (2) grant priority review, and (3) review the supplemental new drug application for pitolisant for people living with idiopathic hypersomnia (IH).

Studies to Evaluate the Efficacy and Safety of Pitolisant in the Treatment of People with IH 

Pitolisant, commercially known as WAKIX®, being developed by Harmony Biosciences, has been shown to improve symptoms in people with IH in well-controlled clinical trials, as well as in real-world data and experience.

Harmony Biosciences’ INTUNE study was a Phase 3 placebo-controlled, double-blind, randomized withdrawal study. Approximately 83% of patients who completed the 8-week open-label treatment period with pitolisant were responders (as defined by a decrease on the Epworth Sleepiness Scale (ESS) of ≥3 points) and experienced a robust clinical response, with an average ESS change from baseline of – 9.4 points. Positive trends favoring pitolisant were also observed in other prespecified endpoints, including the Idiopathic Hypersomnia Severity Scale (IHSS) and Sleep Inertia Questionnaire (SIQ). The mean IHSS Score stayed within the desirable range throughout the long-term extension period. The mean SIQ score also demonstrated sustained improvement throughout the long-term extension period. Finally, the safety and tolerability profile of pitolisant in adult patients with idiopathic hypersomnia was consistent with the established safety profile, and no new safety signals were observed.

Pitolisant has also been evaluated in a real-world independent database analysis (SOMNOBANK) conducted by Yves Dauvilliers. The SOMNOBANK protocol included 64 people living with IH treated with pitolisant between 2010 and 2024. The findings indicated that more than 60% of people with IH in the SOMNOBANK study experienced benefits from pitolisant.

The totality of evidence from the INTUNE study, additional real-world data, and the FDA’s Orphan Drug Designation for pitolisant has provided optimism in the IH community for the approval of pitolisant for adults living with IH.

Incorporating the Perspective of People with IH into the Drug Development Process 

The voice of the patient is critical to the drug development process. The 21st Century Cures Act requires drug developers to include, and FDA to consider, the patient perspective in making approval decisions for new drugs. The IH community has been active in documenting the patient perspective and sharing the IH patient voice with the FDA. These insights into living with IH and rare sleep disorders have been shared with FDA through on-site meetings with advocates, including a Patient Listening Session (August 2022), and, most recently through an externally-led Patient Focused Drug Development meeting, known as Illuminate Hypersomnia (April 2024).

Hundreds of members of the IH community from around the world took part in the Illuminate Hypersomnia initiative, including a four-hour virtual EL-PFDD meeting held on April 11, 2024, and a web-based survey for people living with IH and their care partners and caregivers. This initiative

was a first for the IH community, as was the opportunity for a broad array of IH community members to directly share lived experiences with staff from the FDA, life science companies, academic researchers, healthcare professionals, and other people affected by IH. Key findings that emerged from the community input about the lived experience of IH include:

• Lengthy diagnostic odysseys are the norm,
• An array of symptoms of IH impair daily functioning,
• IH symptoms take a toll on every aspect of life,
• Treating and managing IH is demanding,
• Significant unmet needs remain for treatment, and,
• Stigma and disbelief in the reality of IH add to burden.

As it related to the significant unmet needs for treatment for those living with IH, community members expressed that finding and accessing knowledgeable healthcare professionals was a major challenge that affected diagnosis and treatment options. Even with the help of a caring, informed professional to use available therapies, participants expressed unmet treatment needs. There are substantial gaps in achieving the outcomes that individuals with IH prioritize: feeling more refreshed by sleep and alert with adequate energy and liveliness to go about the day and be involved in meaningful relationships, work, and leisure activities; to stay awake without meds or the “fake awake” feeling of stimulants; to be free of side effects like cardiovascular strain, appetite loss, zombie-like existence, suicidality, and GI distress; and to have fewer restrictions related to medication schedules and travel, due to the nature of some treatments and the controlled nature of others.

The IH Community’s Request of FDA 

Given the clinical trial results, people with IH and the broader rare disease sleep disorder community strongly encouraged Harmony Biosciences to submit its sNDA for pitolisant. We now ask the FDA to promptly give people with IH – who currently have extremely limited treatment options– access to pitolisant as soon as possible.

FDA has emphasized the importance of the patient voice, especially for rare conditions with limited FDA-approved treatment options. The patients, families, and clinicians of the IH community are fully aware of the clinical trial results evaluating the use of pitolisant in IH and are convinced the results demonstrate meaningful benefit and low risk.

We will leave you with a handful of quotes that are representative of the community’s response to existing treatment options, found in the Voice of the Patient Report (September 2024):

• “While using higher doses of stimulants enabled me to take care of the basic things I needed to do in life, that also came with increased side effects, like increased anxiety, irritability, blood pressure, and heart rate.” – Steve Koch, meeting discussion starter
• “Stimulants have not worked for me. They may keep me awake, but it’s like comparing the zombies in the original movies with the zombies in more recent movies. Without medication, most of the time, I feel like a zombie in old movies, moving in slow motion, struggling to think and interact. With stimulants, I’m hyperactive but still struggling to think and interact. The lights are on, but no one is home.” – Written comment submitted by B.M., Connecticut
• “The best days for me aren’t much better than the worst. You’re still reminded that you’re different. For me the best days are the days I can get through without a nap. But those days, too, come at a cost: stimulants, energy drinks, coffee, caffeine pills, and more stimulants. And if you miss one, you’re done. What kind of a best day is that? What kind of a life is that?” – Written comment submitted by A.M., Minnesota
• “Unfortunately, my IH now seems to be getting worse, even with meds…I have no idea what I’m going to do now. I hope and pray that new meds are on the horizon.” – Written comment submitted by L.M., Alabama
• “My current medication doesn’t really work for me, so I’ve had to add coffee, Red Bull, and vitamins that give me energy. I worry about my heart and wonder how long I can keep this up.” – Written comment submitted by P.B., New York 

We urge the FDA to consider the significant unmet need for a non-scheduled drug with a unique safety profile and a simple dosing regimen in IH. We believe that the sNDA for pitolisant should be filed, designated for Priority Review, and reviewed in its entirety. We, as a community, have reviewed the benefit-risk of pitolisant and believe that it should be available as an option for people with IH and their doctors as soon as possible. 

Thank you for your consideration of our community input at this seminal moment in drug development for people living with IH.