Safety Questions Mount Over Vykat XR, the First Approved Drug for Hunger in Prader-Willi Syndrome
Prader-Willi syndrome (PWS) is a rare genetic condition, and its best-known feature is a hunger that never switches off. The medical term for that is hyperphagia.
What causes it: PWS comes from missing or silenced genes on chromosome 15, the copies a child inherits from the father. Those genes help run the hypothalamus, the part of the brain that controls appetite and the feeling of being full.
People with PWS often don’t feel full, even right after a big meal. Their brain keeps signaling that they’re starving.
Seven deaths and dozens of serious adverse-event reports have prompted a former FDA medical officer to call for withdrawal, while clinicians and the manufacturer urge a more measured reading of the data.
Prader-Willi syndrome (PWS) is a rare genetic disorder whose hallmark is hyperphagia, a persistent and intense hunger. In March 2025, the US Food and Drug Administration approved diazoxide choline extended-release tablets (Vykat XR) as the first therapy for hyperphagia in adults and children aged 4 years and older with PWS [4][5]. The drug is a potassium channel activator, and its prescribing information already warns of fluid overload, based on the higher rate of edema seen in clinical trials [4].
The approval was won by Soleno Therapeutics. Neurocrine Biosciences agreed to acquire Soleno in April 2026 in a deal valued at $2.9 billion, which closed on May 18, 2026 [4].
What Has Been Reported
On August 11, 2026, seven PWS clinicians and three patient organizations (the Foundation for Prader-Willi Research, the International Prader-Willi Syndrome Organization and Prader-Willi Syndrome USA) issued a statement alerting clinicians to adverse-event reports in patients taking the drug [4]. According to that statement and contemporaneous reporting, reports submitted to the FDA's Adverse Event Monitoring System included seven deaths and more than 100 other serious adverse events, mostly involving edema, respiratory complications or cardiac complications [2][4]. A caregiver version of the statement says more than 800 people had been prescribed the drug and that the deaths were mostly related to heart or breathing problems, which it ties to fluid retention [3].
On October 13, STAT reported that concern has grown in the two months since. Drawing on case reports obtained through a Freedom of Information Act request, STAT reported that the drug has been linked to the deaths of seven people and the hospitalization of nearly 100 others since approval [1]. STAT also reported that some experts now consider the evidence sufficient to conclude that the drug causes unacceptable harm. Among them is Karen Vogt, a pediatric endocrinologist and former FDA medical officer, who is urging the agency to withdraw Vykat XR from the market [1].
What the Data Can and Cannot Show
All parties, including the critics, agree on a central limitation: spontaneous adverse-event reports cannot establish causation. STAT noted that the case reports "do not prove causality," and that many involved complex medical problems and multiple medications [1]. The clinician statement makes the same point. It notes that everyone who died or had a serious event had other complex health issues, many had severe obesity, and that heart and breathing problems are common in PWS [3].
Two further points of context come from the statement itself. First, people with PWS have an estimated annual mortality of 1% to 3%, so some deaths would be expected in any treated population [3][4]. Second, the pre-approval trials were small, because the disease is rare, and excluded very sick patients. As a result, risks in people with complex conditions were not well characterized [3]. BMO Capital Markets analysts noted that the serious events did not appear to have been seen in clinical testing; in the pivotal Phase 3 trial, edema was mostly low severity and no deaths occurred [5].
Passive reporting systems also cannot give event rates, because neither the true number of events nor the exact number of patients exposed is known. No controlled comparison of treated and untreated patients has been reported in the sources reviewed for this article.
The Concerns and the Response
The clinician statement did not recommend against the drug. Instead, it named risk factors that may warrant extra caution: severe obesity, current or past heart or breathing problems, pre-existing swelling, untreated or poorly controlled sleep apnea, hypoventilation, and a history of severe respiratory infections or pneumonia [3]. Its stated aim was to "increase awareness of the risks for people with PWS" when starting treatment [2].
Neurocrine said in August that Vykat XR has "a compelling risk-benefit profile in the context of a very serious disease" [4]. It said it had reviewed safety and adverse-event data during its due diligence on Soleno, and that it is closely engaged with the FDA, patient advocates and prescribers [4][5]. The accessible portion of the October 13 report did not include a new company statement.
Some clinicians defend the drug's place in care. In an August 17 perspective published by the Foundation for Prader-Willi Research, University of Florida pediatric endocrinologist Jennifer Miller argued that each serious event should be investigated individually [6]. She asked whether prescribing, patient selection, dosing or monitoring may have contributed. She pointed to growth hormone, approved for PWS in 2000, which also had serious adverse events early on and is now standard care [6]. Miller disclosed research funding from Soleno as a Phase 3 trial principal investigator [6].
Clinical and Patient Implications
For now, the main published guidance comes from the PWS clinical community, not from regulators. The clinician statement advises families to make sure the prescriber has PWS expertise or consults someone who does. It also advises reviewing the full prescribing information and having safety testing before treatment, followed by close monitoring [3]. None of the sources reviewed for this article reported a new FDA safety communication or a label change.
What Comes Next
The central question is unresolved: are the reported deaths and hospitalizations caused by the drug, by underlying disease, or by a combination that better patient selection and monitoring could reduce? Answering it will need case-level review and controlled analyses, which passive reports cannot provide. Any regulatory response will be up to the FDA. Vital Biomedical News will update this story as the agency, the company or independent researchers release new data.
This article is for informational purposes only and is not medical advice. Readers should consult their clinician about any treatment decisions.
References
Feuerstein A. Concerns grow on safety issues tied to Neurocrine Biosciences rare disease drug. STAT. October 13, 2026. https://www.statnews.com/2026/10/13/neurocrine-biosciences-prader-willi-vykat-xr/
Feuerstein A. Neurocrine Biosciences rare disease drug possibly tied to safety issues, experts say. STAT. August 12, 2026. https://www.statnews.com/2026/08/12/neurocrine-biosciences-vykat-prader-willi/
Foundation for Prader-Willi Research; International Prader-Willi Syndrome Organization; Prader-Willi Syndrome USA. Clinician Statement: VYKAT XR (diazoxide choline) Safety in Prader-Willi Syndrome (caregiver version). Undated (released August 2026). https://www.fpwr.org/hubfs/Vykat%20adverse%20events%20clinician%20statement%20for%20caregivers.pdf
Kansteiner F. Neurocrine stands by blockbuster hopeful Vykat XR as Prader-Willi docs raise potential safety flags. Fierce Pharma. August 13, 2026. https://www.fiercepharma.com/pharma/neurocrines-blockbuster-hopeful-vykat-xr-tied-possible-safety-risks-prader-willi-clinicians
BioSpace. Deaths reported after treatment with Neurocrine's approved Prader-Willi drug. BioSpace. August 12, 2026. https://www.biospace.com/drug-development/deaths-reported-after-treatment-with-neurocrines-approved-prader-willi-drug
Miller J (contributed perspective). Balancing Benefit, Risk, and Access to VYKAT XR. Foundation for Prader-Willi Research. August 17, 2026. https://www.fpwr.org/blog/balancing-benefit-risk-and-access-to-vykat-xr