When Lara Pullen’s son was diagnosed with Prader-Willi syndrome, a rare genetic condition that causes morbid obesity in children, she began to read through what scientific studies she could find.
Pullen, who has a doctorate in immunology, knew her way around research papers. As she read, she became struck that despite widespread notions of the disease, the data paints a different story.
Endocrinologists have typically treated Prader-Willi because of its hallmark associations with intense appetite, diabetes, and obesity. However, it is a complex condition that involves muscle weakness, developmental and intellectual disability, sleep apnea, and daytime sleepiness.
Everything pointed Pullen back toward the nervous system. One thing that caught her attention was that the histamine 3 receptor, which is found in the brain, plays a role in regulating sleep and wake states, hunger, alertness, anxiety, and REM sleep. The more she read, the more she was taken by how the histamine 3 receptor aligns with different problems in Prader-Willi patients.
What followed shows how patients, regulators, and drug developers who are willing to think in new ways can drive advancements for patients with rare conditions.
“Just because something has been done one way in the past doesn’t mean it has to be done that way,” said Pullen, who founded the Prader-Willi patient group Chion Foundation.
Pullen argued Prader-Willi syndrome symptoms are similar to what is seen in narcolepsy with cataplexy, a rare condition involving daytime sleepiness and sleep apnea.
It so happens that in 2016, the European regulators approved pitolisant, a treatment for narcolepsy that targets the histamine 3 receptor. Pullen reasoned the drug might benefit patients with Prader-Willi.
Pullen’s case was strengthened by the work of TREND Community, a platform for scouring patient insights from social media that found a link between Prader-Willi syndrome and the symptoms of daytime sleepiness. Maria Picone, co-founder and CEO of TREND Community, has a daughter with Prader-Willi syndrome.
Pullen obtained a prescription for the drug from her son’s physician, purchased it in Germany, and brought it into the United States under a personal importation route allowed at the FDA’s discretion. She enlisted other families to do so as well. The families agreed to document their experience using the TREND Community platform, which allowed caregivers to track and report on their experiences using pitolisant.
In a clinical vignette in the March-April 2019 issue of the Journal of Pediatric Pharmacology and Therapeutics, Pullen and her co-authors reported that pediatric patients with Prader-Willi who used pitolisant had decreased daytime sleepiness and improved cognition. They suggested the drug had the potential to relieve symptoms associated with the condition.
Credit where it’s due
The work of Pullen and other families is detailed in the recent Global Genes rare disease report “NEXT: Imagining the Future of Rare Disease.” Because of them, pitolisant is in clinical studies as a potential treatment for Prader-Willi syndrome.
Harmony Biosciences, which won FDA approval for the drug as a treatment for narcolepsy in August 2019, began a pharmacokinetic and pharmacodynamic study at the end of 2019 to determine appropriate dosing. It is expected to begin recruiting patients for a mid-stage clinical study in the first quarter of 2020.
Despite the long timelines and high cost of drug development, Pullen commends the work to repurpose pitolisant from a weak signal to drug in patients in four years and at relatively little costs. It shows how caregivers looking at real-world data can change the understanding of a disease, how novel technology such as TREND Community’s software can capture critical data about the patient and caregiver experience, and how a growing willingness among drugmakers and regulators to work through new pathways can bring treatments to rare disease patients.
“Absent an approved therapy, patients and caregivers are trying anything and everything to find an improved quality of life,” said TREND’s Picone. “If you go that extra step and contribute your data, you can really move the needle.”