Obesity has many drivers, but for those with a particular rare metabolic disorder, the root cause is genetic. These patients develop ravenous hunger unsatisfied by any amount of food. The constant eating and food-seeking behavior leads families and caregivers to restrict food access by locking refrigerators, pantries, even trash cans.
This rare disease, Prader-Willi syndrome, has been described in medical literature for nearly 70 years. But even as medical understanding of the disorder grew, efforts to develop a drug to treat it have fallen short — until now. Soleno Therapeutics drug Vykat XR has received the first FDA-approval for Prader-Willi. The regulatory decision announced late Wednesday covers the treatment of the excessive hunger, called hyperphagia, in Prader-Willi patients age 4 and older.
Prader-Willi, named for the Swiss physicians who described the disorder in a paper published in 1956, is caused by lack of expression of certain genes that play a role in regulating feelings of hunger and satiety. Prader-Willi patients face a greater risk of cardiometabolic issues and other complications that stem from obesity. Redwood City, California-based Soleno estimates 300,000 to 400,000 people worldwide have the disorder. Signs of the disease typically start showing when a patient is age 7 or 8, but can occur earlier, Soleno CEO Anish Bhatnagar said during a Wednesday evening conference call.
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“This is essentially your brain telling you that you’re starving despite having eaten,” he said. “Hyperphagia is a truly terrible condition for which no approved treatments have existed until today’s approval of Vykat XR.”
Vykat’s main pharmaceutical ingredient is diazoxide choline. Diazoxide is a more than 50-year old drug still used today to manage hypoglycemia caused by hyperinsulinism. This now generic medicine, marketed by Teva Pharmaceutical as Proglycem, is an oral suspension taken three times daily. Soleno’s drug is formulated into an extended-release tablet that leads to lower peak concentrations in the blood compared to Proglycem. This property allows for gradual release of the active ingredient, enabling once-daily dosing.
The exact way Vykat works to treat hyperphagia is unknown. But diazoxide choline activates potassium channels that play a central role in regulating various physiological processes. In Prader-Willi, these processes may contribute to increase in appetite and other manifestations of this disease, Soleno said in its annual report. Targeting potassium channels in the brain, pancreas, and fat tissue, offers the potential to reduce appetite and aggressive food seeking while also reducing the accumulation of excess body fat and the progression to insulin resistance.
Soleno’s drug failed its first pivotal test. In a 13-week, placebo-controlled Phase 3 study enrolling 127 patients, results released in 2020 showed the drug did not meet the goal of showing a statistically significant change in hyperphagia. But based on significant improvements on secondary goals, the company analyzed data collected from before the onset of the Covid-19 pandemic. This analysis showed statistical significance on the main goal and all secondary goals. Furthermore, the open-label extension study showed statistically significant reduction in hyperphagia scores and other measures of Prader-Willi compared to the natural history of the disease.
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With the agreement of the FDA, Soleno amended the study protocol to focus on patients in the open-label extension study. These 77 patients had received the study drug for an average of 3.3 years. Participants were randomly assigned to either continue receiving Vykat or be withdrawn from the study drug and switched to placebo. Results showed those switched to placebo experienced statistically significant worsening of hyperphagia compared to those who continued receiving Vykat. These results were the basis for the FDA submission.
Prader-Willi has been a tough area for drug research. Zafgen and Millendo Therapeutics stopped work on their respective Prader-Willi drugs following clinical trial setbacks. Levo Therapeutics developed a drug intended to increase levels of oxytocin, a hormone that regulates appetite. In 2022, the FDA rejected Levo’s drug and asked for another clinical trial. That program is now in late-stage clinical development under another company, Acadia Pharmaceuticals.
Aardvark Therapeutics, which raised $94 million from its IPO last month, is taking yet another approach to Prader-Willi. The company’s drug binds to TAS2 receptors in the gut to prompt secretion of hormones that suppress hunger. A Phase 3 test of Aardvark’s twice-daily pill is ongoing in patients who have hyperphagia associated with Prader-Willi; preliminary data are expected in 2026.
Soleno expects Vykat will launch in April. This drug, which is dosed according to patient weight, will be available in three dosage strengths. The product’s list price is $5.92 per mg. Based on the average weight of patients in the clinical trial, the annual cost works out to about $466,200. But Chief Commercial Officer Meredith Manning said the company expects initial uptake of the new drug will be driven by children and young adults who weigh less than the average weight in the clinical trial, which will result in a lower cost.
Manning said Soleno is speaking with payers to secure comprehensive coverage. Because Vykat is a rare disease product, she expects payers will require a prior authorization and genetic confirmation of the disease. Soleno also aims to bring Vykat to Prader-Willi patients in other markets. A European regulatory submission is planned for the second quarter of this year. Bhatnagar said a decision about whether to seek partners for commercialization outside of the U.S. will be made after that submission.
Based on an analysis of medical claims data, Soleno calculates there are about 12,000 Prader-Willi patients in the U.S. An estimated 10,000 of these patients are eligible for Vykat based on the product’s label. Though diazoxide is already available via Teva’s Proglycem, the Vykat label warns against substituting the lower-cost generic medication for the new Soleno product. Bhatnagar noted that there are differences in the drug properties and the way each medication works in the body.
“We get asked all the time, can someone use diazoxide oral suspension,” he said. “The answer — the FDA agrees with that — is no you cannot, because the pharmacokinetic profiles are very different.”
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