Rare metabolic disease that causes childhood obesity gets the first FDA-approved drug
Obesity has many drivers, but the underlying cause is genetic for patients with special rare metabolic diseases. These patients develop a feverish sense of hunger without being satisfied with any food. Continuous diet and food seeking behaviors lead families and caregivers to limit access to food by locking in refrigerators, pots and pans and even trash cans.
This rare disease, namely Prad Willie Syndrome, has been described in the medical literature for nearly 70 years. But even medical understanding of the disease has intensified, and until now, efforts to develop drugs to treat it are lacking. Soleno Therapeutics Drug vykat XR has received the first FDA approval from Prader-Willi. The regulatory decision announced late Wednesday covers treatment for excessive hunger (called Hyperphagia) in Prader-Willi patients aged 4 and older.
Prader-Willi, named after a Swiss doctor who described the disease in a 1956 paper, was caused by the lack of expression of certain genes that play a role in regulating hunger and fullness. Prader-Willi patients are at greater risk of cardiac metabolic problems and other complications, which are derived from obesity. Soreno, based in Redwood, California, estimates that between 300,000 and 400,000 people worldwide suffer from the disease. Signs of the disease usually start to show when patients are 7 or 8 years old, but can occur earlier, Sorenault CEO Anish Bhatnagar said on a conference call Wednesday night.
“Essentially, it’s your brain that tells you that despite eating, you’re still starving,” he said. “Papagia is a truly terrible condition that there is no approved treatment until today’s approval of Vykat XR.”
The main pharmaceutical ingredient of Vykat is choline dioxide. Nitroxide is a drug that is still used for more than 50 years to manage hypoglycemia caused by hyperinsulin. General Medicine, now sold by Teva Pharmaceutical as Proglycem, is to perform oral suspension three times a day. Soreno's drug is formulated as an extended release tablet, with a lower peak concentration in the blood than the introductory model. This property allows for the gradual release of the active ingredient to achieve once-daily dosing.
The exact method of Vykat can be used to treat magnification. However, choline dianitrogen oxidation activates potassium channels that play a central role in regulating various physiological processes. In Prader-Willi, these processes may help increase appetite and other manifestations of the disease, Soreno said in his annual report. Targeting potassium channels in the brain, pancreas and adipose tissue provides the potential to reduce appetite and eat actively, while also reducing the accumulation of excess body fat and progression of insulin resistance.
Soleno's drug failed its first critical test. In a 13-week placebo-controlled phase 3 study, 127 patients were recruited, and the 2020 release showed that the drug did not achieve the goal of showing statistically significant changes in magnification. However, based on significant improvements to secondary goals, the company analyzed data collected before the COVID-19 pandemic began. This analysis showed statistical significance for both the primary and all secondary objectives. Furthermore, open label extension studies showed statistically significant reductions in Padia scores and other Prader-willi compared to the natural history of the disease.
According to FDA's consent, Soleno modified the study protocol to focus on patients in the open-label extension study. These 77 patients received an average of 3.3 years of study medication. Participants were randomly assigned to continue receiving Vykat or withdrawn from the study drug and converted to placebo. The results showed that those who turned to placebo experienced statistically significant worsening compared to those who continued to receive Vykat. These results are the basis for the FDA submission.
Prader-Willi has been a difficult area of drug research. Zafgen and Millendo Therapeutics stopped their respective Prader-Willi drugs after a setback in clinical trials. Levo Therapeutics has developed a drug designed to increase levels of oxytocin, a hormone that regulates appetite. In 2022, the FDA rejected Levo's drug and asked for another clinical trial. The program is now in late-stage clinical development of another company, Acadia Pharmaceuticals.
Aardvark Therapeutics, which raised $94 million from the IPO last month, is taking another approach to Prader-Willi. The company's drugs bind to Tas2 receptors in the gut to promote hormone secretion that inhibits hunger. Grumpy patients associated with Prader-willi are undergoing a Phase 3 test of Aardvark two pills; preliminary data are expected to be conducted in 2026.
Soleno expects Vykat to be launched in April. The drug is dosed based on the patient's weight and can provide three dose intensity. The product is priced at $5.92 per milligram. The annual cost is about $466,200 based on the average weight of the patient in the clinical trial. But chief business officer Meredith Manning said the company expects the initial absorption of new drugs to be driven by children and young people who weigh less than the average weight of clinical trials, which will result in lower costs.
Manning said Sorenault is talking to the payer to ensure full coverage. Since Vykat is a rare disease product, she expects the payer to require prior authorization and genetic confirmation of the disease. Soleno also aims to bring Vykat to Prader-Willi patients in other markets. European regulatory submissions are planned in the second quarter of this year. Bhatnagar said that after submission, a decision will be made on whether to seek partners for commercialization outside the United States.
Based on an analysis of medical claims data, Sorenault calculated that there are approximately 12,000 Prader-Willi patients in the United States, with an estimated 10,000 of these patients eligible for Vykat based on the product’s label. Although dinitrogen oxides have been obtained through Teva's Proglycem, the Vykat tag warns against replacing lower-cost generics with new Soleno products. Bhatnagar points out that there are differences in the properties of drugs, how each drug works in the body.
“We're always asked that someone can use the oxynitride vent hanging,” he said. “The answer – the FDA agrees with that – you can't, because the pharmacokinetic profile is very different.”
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