Phase 2 Trial Begins to Evaluate Pitolisant for DM1

At the end of June 2021, pharmaceutical company Harmony Biosciences Holdings, Inc. (“Harmony”) shared the initiation of a Phase 2 clinical trial via news release . During the trial, the researchers will evaluate the safety, efficacy, and tolerability of pitolisant (WAKIX) for adults with myotonic dystrophy type 1 (DM1). Within the trial, there will be a specific focus on the ability of pitolisant to reduce non-muscular symptoms, including excessive daytime sleepiness (EDS) and impaired cognitive function.


Pitolisant, also known as its branded name WAKIX, was described by the Pharmacy Times as:

a selective histamine 3 receptor antagonist/inverse agonist that increases the synthesis and release of histamine, a wake-promoting neurotransmitter in the brain.

The orally administered treatment has already been approved for the treatment of EDS in patients with narcolepsy or cataplexy. Thus far, pitolisant has received both Orphan Drug and Breakthrough Therapy designations in regards to narcolepsy or cataplexy.

Pitolisant should not be used by patients with long QT syndrome or similar conditions. Additionally, this therapy is contraindicated for patients with hepatic (liver) or renal (kidney) impairment. Although prior research has shown the drug to be relatively safe and well-tolerated, some side effects may occur. These include:

  • Anxiety or irritability
  • Nausea
  • Abdominal pain
  • Appetite loss
  • Dry mouth
  • Insomnia
  • Upper respiratory infections
  • Headache
  • High heart rate

The Phase 2 Trial

Within this newly initiated Phase 2 study, researchers are exploring the safety, efficacy, and tolerability of pitolisant. Patients enrolled in the study range from age 18 to 65. Altogether, 135 patients with DM1 enrolled in the study. During the course of the study, patients will receive either a placebo or a high or low dose of pitolisant. Following the initial 3-week period, all patients will receive stable doses for 8 weeks. The research looks to understand how pitolisant reduces fatigue, sleepiness, and other symptoms. Ultimately, Harmony hopes to share data in the latter part of next year. 

Myotonic Dystrophy

There are two forms (1 and 2) of myotonic dystrophy, a genetic muscle disorder causing progressive muscle wasting and weakness. An abnormally expanded section on the DMPK gene causes DM1, a more severe form of this condition. In this form, the muscle weakness often affects the face, hands, neck, and lower legs. Alternately, ZNG9 mutations cause DM2, the milder form. In this form, the muscle weakness often affects the shoulders, hips, elbows, and neck. Regardless, patients with myotonic dystrophy are unable to relax certain muscles after use, instead experiencing sustained muscle contractions.

Myotonic dystrophy is considered the most common form of adult-onset muscular dystrophy. An estimated 90% and 60% of patients experience EDS or impaired cognitive function, respectively. Additional symptoms include:

  • Voluntary muscle weakness
  • Myotonia (inability to relax muscles at will)
  • Difficulty swallowing
  • Type 2 diabetes
  • Infertility (in males)
  • Cataracts
  • Apathy
  • Clubfoot
  • Developmental delays
  • Learning disabilities
  • Impaired cognitive function
  • Abnormal heart rate
  • Gallstones
  • Breathing problems (often found in congenital myotonic dystrophy)
  • Constipation

Patients with myotonic dystrophy may also experience pregnancy and labor-related complications due to abnormal or weakened uterine muscles.

Learn more about myotonic dystrophy.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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