Ali Foley Shenk vividly recalls the anxiety of a frightening moment when her 10-year-old son, Dean, devoured an entire 20-ounce box of raisins in mere seconds after they’d mistakenly left the pantry open. Their immediate concern was a potential bowel impaction, prompting a hurried trip to the emergency room.
The situation is especially poignant for Foley Shenk, who resides in Richmond, Virginia. When Dean was born, he was extremely weak and reliant on feeding tubes due to an inability to suck or swallow. Diagnosed with Prader-Willi syndrome – a rare genetic disorder – he previously showed little interest in food. However, medical professionals cautioned that as he would grow, his hunger could become unmanageable, leading him to gain excessive weight or, worse, eat until his stomach ruptured. “It’s crazy,” Foley Shenk remarked, reflecting on the dramatic shift in Dean’s needs. “All of a sudden, they flip.”
Prader-Willi syndrome impacts approximately 20,000 individuals in the United States. Its most alarming symptom is hyperphagia, an overwhelming and insatiable hunger that drives caregivers to take extreme measures, such as padlocking cupboards and securing trash cans. Historically, treatment options were limited to growth hormone therapy, which aimed to manage weight but did not alleviate appetite.
In March, however, the Food and Drug Administration approved Vykat XR, an extended-release formulation of diazoxide choline, to help control this relentless hunger. This development arrives alongside a wave of new obesity medications, including GLP-1 agonists like Ozempic and Wegovy, which are yielding significant results for millions of Americans battling obesity.
Jack Yanovski, a senior obesity researcher at the National Institutes of Health and co-author of studies related to Vykat XR, emphasized the complexity of obesity, stating, “It only makes sense that it’s complex to treat.” He explained that obesity encompasses various factors, including environmental and genetic influences.
The field of obesity medicine appears poised to evolve similarly to treatments for chronic conditions like high blood pressure or diabetes, potentially offering various effective options for different patient types. Notably, research indicates that about 15% of participants in GLP-1 trials did not respond favorably, and preliminary findings suggest the medication doesn’t significantly benefit those with Prader-Willi syndrome.
Concerns are mounting, however, as the Trump administration cuts funding for health research, jeopardizing vital studies related to obesity. Robert F. Kennedy Jr., the Secretary of Health and Human Services, promotes a health initiative focused on diet and lifestyle, while federal health research funding is facing constraints. University laboratories are bracing for budget cuts, FDA layoffs are occurring, and researchers specializing in rare conditions fear negative repercussions for wider medical advancements. “That whole thing is likely to get disrupted now,” commented Theresa Strong, research director for the Foundation for Prader-Willi Research.
Despite these budgetary concerns, HHS spokesperson Andrew Nixon assured that no NIH funding for Prader-Willi syndrome research had been reduced, stating, “We remain committed to supporting critical research into rare diseases and genetic conditions.”
Still, research teams are facing challenges; Strong noted that key contacts at the FDA, whom she had spent years educating about Prader-Willi syndrome, have departed the agency. Some groups are contemplating relocating their labs to Europe due to uncertainty in U.S. funding.
Dean Shenk’s life has begun to change thanks to innovations in hunger and obesity research. During the Vykat XR clinical trial, his anxiety surrounding food diminished so significantly that his parents started leaving kitchen cupboards unlocked. Jennifer Miller, a pediatric endocrinologist at the University of Florida and co-leader of the Vykat XR trials, has witnessed life-altering progress in many of her patients since the inception of the drug trial in 2018. As a result, several adults with the syndrome are now living independently, pursuing higher education, and embarking on careers – milestones that felt unattainable before. “It opens up their world in so many ways,” Miller remarked.
Over her 26 years of practice, Miller has seen the extreme challenges faced by patients with Prader-Willi syndrome. One individual consumed a vast four-pound bag of dehydrated potato flakes; another devoured all 10 frozen pizzas from a Costco pack. Others have faced dire consequences while in pursuit of food, including severe injury or death.
Dean, who also experiences narcolepsy and cataplexy, has benefited from Vykat XR; his hyperphagia is reportedly under control, resulting in an increase in lean muscle, a decrease in body fat, and improved bone health. His mother, Foley Shenk, noted that even Dean’s skin-picking behavior, previously linked to anxiety over his hunger, has ceased.
Vykat XR does not cure Prader-Willi syndrome, but it works by calming overactive neurons in the hypothalamus that generate neuropeptide Y, a potent hunger signal. Anish Bhatnagar, CEO of Soleno Therapeutics, explained, “In Prader-Willi, that off switch doesn’t exist. It’s literally your brain telling you, ‘You’re starving,’ as you eat.”
Unlike Vykat XR, GLP-1 drugs mimic a gut hormone that promotes feelings of fullness by slowing digestion. The average yearly cost for Vykat XR stands at an astounding $466,200, a significant expense even for rare disease treatments. Soleno has reassured the public that they anticipate broad insurance coverage and minimal copayments, and currently, they are supplying the drug free of charge to trial participants until more insurers provide reimbursement.
Following the FDA’s approval, Soleno’s stock surged by 40%, maintaining a valuation close to $4 billion as of June. While Vykat XR specifically helps a limited patient demographic, obesity researchers are optimistic that the underlying biology may illuminate new treatment avenues.
Jesse Richards, an internal medicine physician and the director of obesity medicine at the University of Oklahoma-Tulsa, believes that understanding targeted therapies for rare genetic obesity can shed light on the brain’s appetite-regulating pathways.
The future of obesity treatment may already be on the horizon, with two significant Phase 3 clinical trials for Prader-Willi syndrome currently being conducted by Acadia Pharmaceuticals and Aardvark Therapeutics, each exploring different mechanisms. Additionally, many trials for general obesity are actively recruiting despite the prevailing uncertainties in U.S. medical research funding.
For patients like Dean, this progress holds considerable promise. Nearly six years into treatment, the now 16-year-old has transformed into a calmer, happier young man, as reported by his mother. With reduced impulses to overeat, he now cultivates friendships, engages more deeply in school, and nurtures hobbies such as Star Wars and American Ninja Warrior, alongside a newfound appreciation for avocados. “Before the drug, it just felt like a dead end. My child was miserable,” said Foley Shenk. “Now, we have our son back.”