Roughly a year and a half after the approval of Vykat XR, a group of clinicians with deep ties to the Prader-Willi syndrome (PWS) community is flagging potential concerns about the safety of the rare disease med, acquired in Neurocrine’s $2.9 billion buyout of Soleno Therapeutics last spring.
The package insert for Vykat XR (diazoxide choline)—a potassium channel activator that became the first drug approved to treat the sensation of insatiable hunger, or hyperphagia, in PWS in March 2025—already cites the risk of fluid overload, based on an increased incidence of edema seen during clinical trials.
Since becoming more widely available, additional reports of edema and related complications in patients taking Vykat XR have been posted to the FDA’s Adverse Event Monitoring System (AEMS), including seven reports of death and more than 100 other reports of serious adverse events, mostly tied to edema, respiratory and cardiac complications.
The adverse event trend, which doesn't establish that Vykat XR caused the events, was flagged in a statement (PDF) from PWS patient organizations the Foundation for Prader-Willi Research, the International Prader-Willi Syndrome Organization and Prader-Willi Syndrome USA. The issue was first reported by Stat News earlier on Wednesday.
In the letter, backed by the insights of seven PWS clinicians, the patient organizations noted that cases resulting in death or other serious outcomes were marked by “complex medical issues,” plus the use of multiple medications and, in many instances, pre-existing obesity.
“It cannot be determined from these adverse event reports whether these deaths and complications are directly related to VYKAT XR treatment or if they are part of the underlying challenges of PWS,” the clinician statement reads.
“However,” it continues, “these particular complications do not appear to be common among individuals providing medical information to the caregiver-reported outcomes in the Global PWS Registry, recognizing that the Global PWS Registry population may differ from the VYKAT XR-treated cohort with respect to disease severity or clinical management.”
By releasing the statement, the clinicians and patient groups said they aim to “increase awareness of the risks for people with PWS” when starting Vykat XR.
Neurocrine, for its part, continues to stand behind its drug, with a spokesperson telling Fierce that Vykat XR boasts "a compelling risk-benefit profile in the context of a very serious disease."
Further, the company "conducted extensive diligence on the safety profile, including adverse event data, during our process to acquire Soleno," the Neurocrine representative said in an emailed statement. "We are closely engaged with the FDA, patient advocacy communities and prescribers to continue to assess all available data from postmarketing surveillance as the prescribing population expands."
The clinician letter, meanwhile, stopped well short of drawing a causal link between Vykat XR and the deaths and side effects reported to the FDA.
Moreover, many medical complications are common in people with PWS, the clinicians and patient groups wrote, especially when patients are also dealing with obesity and uncontrolled sleep apnea.
"Compared to the general population, mortality is higher at all ages in people with PWS, and published data suggest that each year 1-3% of people with PWS die in all age groups," the letter states.
The clinician statement calls for further study into multiple potential risk factors for patients taking Vykat XR, including severe obesity, underlying heart problems, pre-existing edema or fluid retention, serious breathing issues, poorly controlled sleep apnea and a history of severe respiratory infections or pneumonia.
"There may be other risk factors of which we are not yet aware," the letter writers said.
In its own statement, Neurocrine reiterated its commitment to patient safety, as well as the role it believes Vykat XR can play in helping patients and families manage PWS.
As for the clinician letter, the doctors and patient groups said they were grateful for drugmakers striving to develop new treatments for Prader-Willi.
“We welcome long-term follow-up clinical studies focused on safety and efficacy of all licensed and potential treatments, including post licensing surveillance, to improve the quality of life for individuals with PWS and their families,” the statement concluded.
Neurocrine’s share price was down more than 3% on Thursday morning after the U.S. market opened.
Vykat XR’s nod was won by Soleno Therapeutics, which picked up a green light in March 2025 for its drug to treat children ages 4 and older and adults with PWS, which leads to low muscle tone, short stature and intellectual and developmental challenges.
As a potassium channel activator, Vykat XR was specifically approved to combat hyperphagia, or an insatiable sensation of hunger associated with the rare genetic disorder.
About a year later, Neurocrine swooped in with a $2.9 billion deal, announcing in April 2026 that it would acquire Soleno and its drug, upon which it pinned blockbuster sales hopes. The acquisition closed May 18.
While Evercore ISI analysts agreed at the time that the “timing, asset profile, and role” that Vykat XR could play in the Neurocrine narrative “all fit well,” other analysts appeared more skeptical about the long-term sales prospects of the medicine when the deal was first announced.