Prader-Willi Syndrome may get a new treatment option in late December

FDA is reviewing intranasal carbetocin, which is designed to treat specific symptoms of this complex genetic disorder

December 6, 2021
Prader-Willi syndrome (PWS) is a genetic, multi-system disorder that affects approximately 9,000 to 10,000 individuals in the United States. Its symptoms and their severity vary from person to person.  The symptoms are likely due to a dysfunction in the hypothalamus. This is a small organ or gland in the base of the brain that regulates hunger, satiety, pain, emotions and fertility.1

There is no cure for PWS. Common characteristics of PWS1 include:

  • delayed developmental motor and language milestones
  • short stature
  • small genitals
  • behavioral challenges like:
    • obsessive compulsive behavior
    • anxiety
    • severe hyperphagia (extreme hunger) and
    • impaired satiety

The combination of behavioral challenges can lead to life-threatening obesity. Food-seeking behaviors may include:

  • eating garbage
  • eating frozen food
  • stealing and hoarding food

A decreased ability to vomit and increased tolerance of pain can promote binging.

Current treatments

Treatment plans are directed toward the specific symptoms presented in each individual. Early intervention and strict maintenance to treatment can greatly improve overall health and quality of life. Treatment often includes the coordinated efforts of a team of specialists.

Specific treatments may be prescribed for hypogonadism, osteoporosis, hypothyroidism, adrenal insufficiency and sleep apnea. Most children with PWS use recombinant human growth hormone.1

Hyperphagia/obesity:1 If approved, intranasal carbetocin will be the first medication approved for symptoms associated with PWS. Other treatment options  for these symptoms include management of eating and treatment of obesity’s co-morbidities:

  • Strict limitation of food intake is the cornerstone of effective management.
  • Caloric goals are set and access to food limited using physical barriers (locks).
  • Close supervision is necessary.
  • Pharmacotherapy with anorectic agents, selective serotonin reuptake inhibitors (SSRIs), or topiramate has not been effective in controlling appetite or weight gain.
  • Obesity-related problems including high blood pressure, high triglycerides and gallstones are generally treated as they would be in other patients with obesity.

Overview of internasal carbetocin

Intranasal carbetocin is a selective oxytocin receptor agonist. Ocytocin has been shown to play a central role in social behaviors.2 PWS is associated with decreased oxytocin levels. (There are many research projects studying ocytocin as a therapeutic agent in PWS.3)

The Phase 3 trial had 119 participants. It was a multi-center, randomized, double-blind, eight-week, placebo-controlled trial, designed to evaluate the safety, effectiveness, and tolerability of intranasal carbetocin in patients aged 7-18 with PWS.4-6 Patients were randomly assigned to one of three groups to be given:

  • Intranasal carbetocin 9.6mg three times a day with meals
  • Intranasal carbetocin 3.2mg three times a day with meals
  • intranasal placebo three times a day with meals

The study used two scales for efficacy measures:

  • Hyperphagia Questionnaire for Clinical Trials (HQ-CT): Validated questionnaire to measure hyperphagia; the range of scores is 0-36 with scores above 13 typically considered to be moderate to severe hyperphagia.
  • Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS): clinician rated, semi-structured inventory of specific symptoms and symptom severity in pediatric obsessive-compulsive disorder (OCD). Scores can range from 0-40 with 14-24 considered moderate, 25-30 moderate-severe and over 30 severe.

The two primary efficacy measures were changes in baseline to week eight in either HQ-CT score or CY-BOCS score (9.6mg versus placebo). The primary efficacy endpoint was not met as there was no statistical significance found in either the HQ-CT or CY-BOCS score.

The study did meet one secondary efficacy measure:  changes in HQ-CT score from baseline to week eight at the 3.2mg dosage compared to placebo); however it did not for the CY-BOCS score4-6

  • Statistical significance was achieved with the 3.2mg dose in the HQ-CT score
  • No statistical significance was seen with the 3.2mg dose in the CY-BOCS score

PDFUA date:          December 31, 2021
Benefit/ROA:         Pharmacy benefit/Intranasal spray

Support from the Foundation for Prader-Willi Research (FPWR)

Executives from the FPWR sent the FDA a letter in support of Intranasal carbetocin in May. They cited the importance of the results of the secondary endpoint. They also noted anecdotal evidence reported from trial participants of continued benefits from the drug following the study.7

FDA Psychopharmacologic Drugs Advisory Committee (AdCom)

On Nov. 4, 2021, the FDA Psychopharmacologic Drugs AdCom concluded 12-1 that the studies conducted did not show substantial evidence of efficacy.

Prime monitors the extended drug pipeline for PWS8, 9

The drug pipeline is full of new, groundbreaking specialty drugs that may help members live better and feel well. Prime focuses on clinical strategies designed to keep clients ahead of drug trends — because it’s easier to manage change when you see it coming.


  1. About Prader-Willi Syndrome: A clear explanation of PWS symptoms, causes, diagnosis, genetics, treatments & research. Foundation for Prader-Willi Research. Accessed at:
  2. Busnelli, M., Bulgheroni, E., Manning, M., Kleinau, G., & Chini, B. (2013). Selective and potent agonists and antagonists for investigating the role of mouse oxytocin receptors. The Journal of pharmacology and experimental therapeutics, 346(2), 318–327.
  3. Identification of Critical Periods for the Neurodevelopmental and Behavioral Effects of Oxytocin. © 2020. Foundation for Prader-Willi Research. Accessed at:
  4. Levo therapeutics announces top-line results from Phases 3 CARE-PWS study of LV-101 (intranasal carbetocin) for the treatment of Prader-Willi syndrome. Accessed in October 2021 at:
  5. Topline results of the CARE-PWS Phase 3 study: intranasal carbetocin improves hyperphagia and anxiety and distress symptoms in Prader-Willi Syndrome (PWS). Accessed in October 2021 at:
  6. Hyperphagia, anxiety eased with carbetocin in patients with Prader-Willi syndrome. Accessed in October 2021 at:;
  7. PWS Community Letter to the FDA: FPWR and PWSA|USA Request Regulatory Flexibility & Review of NDA for Intranasal Carbetocin. May 25, 2021. Accessed at:
  8. Search terms: carbetocin/PWS. Accessed in October 2021.
  9. Radius Health announces plans for global prader-willi syndrome pivotal study. Accessed in October 2021 at:

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