Pitolisant: a novel therapy for narcolepsy and other rare neurological disorders

Through the application of first principles to drug design, a novel orphan drug has been created for treating narcolepsy, excessive daytime sleepiness (EDS) and Prader-Willi Syndrome.

Narcolepsy is a disabling, long-term neurological disease that affects 1 in 2,000 individuals (approximately 30,000 people in the UK and 165,000 people in the USA).

It significantly decreases the quality of life of the affected individuals, with two-thirds of patients being unable to work. Prior to the commercial release of pitolisant, there was an unmet need for an effective, safe, and tolerable treatment regime in the management of narcolepsy.  

Professor Robin Ganellin (UCL Department of Chemistry) had been researching with biologists since 1964, when he worked in industry, focusing on histamine receptors. Upon joining UCL, Professor Ganellin started collaborating with French neuroscientist Professor Jean-Charles Schwartz. His research group in Paris identified histamine H3 receptors that controlled histamine transmission and demonstrated that histamine was a neurotransmitter that probably led to wakefulness.

Professor Ganellin’s research group synthesized novel chemical compounds that were tested in Paris. After many years without discovering a drug, he took a different, first principles approach to generate a type of chemical structure that led to Wakix™. 

This discovery led to the development and commercialisation of pitolisant (Wakix™) by Bioprojet in Europe and Harmony Biosciences in the USA. Pitolisant, the first in its class, has changed the way narcolepsy (with or without cataplexy) is managed and dramatically improved the quality of life for those suffering from the condition.  

Production of Pitolisant 

Pitolisant (Wakix™) is the first - and so far, only - medicament to be marketed that acts on the histamine H3 receptor. This leads to increased histamine transmission in the brain, enhancing wakefulness and alertness and decreasing cataplexies in patients with narcolepsy.

A patient reported: “Wakix™ is the most wonderful drug I’ve known over my 50 years suffering narcolepsy. If I’d been able to have it 30 years ago my life would have been so much easier.”

Pitolisant represented the first new therapy in over a decade for the treatment of narcolepsy. After being granted marketing authorisation by the European Medicines Agency's Committee for Medicinal Products in 2016, pitolisant received NHS appraisal by the National Institute for Clinical Excellence (NICE) and is deemed to be 42% more cost-effective for the NHS. 

In August 2019, the Food and Drug Administration (FDA) approved pitolisant (trade name Wakix™, Harmony Biosciences) for use in the USA to treat EDS in adult patients with narcolepsy. As of June 30, 2020, over 1,750 unique health care providers have prescribed Wakix™ since it became available in November 2019, representing 2,700 unique patients.  

As direct consequence of the licensing agreement between Bioprojet and Harmony Biosciences, Harmony Biosciences raised $270 million in equity funding from 29 investors and secured a $200 million debt facility to provide additional working capital to fuel the company’s continued growth.  Since its launch in November 2019, the drug has accounted for net sales of $57.8 million for Harmony Biosciences. 

Links

• Professor Robin Ganellin's academic profile  
• UCL Department of Chemistry
• UCL Faculty of Maths & Physical Sciences 
• UCL Faculty of Maths & Physical Sciences REF 21

Image 

• Image credit: iStock FilippoBacci