On behalf of our Research and Clinical Trials Committee, Tony Holland, President Emeritus, shares reflections on recent progress and ongoing challenges in the development of treatments for hyperphagia in people with Prader-Willi syndrome.
In March 2025, the USA Food and Drug Administration (FDA) approved Vykat XR for the treatment of hyperphagia (increased eating behaviour) in people with Prader-Willi syndrome (PWS). This was the first treatment to be approved for this indication and the first new medical treatment to be approved for PWS since growth hormone over 20 years ago. This was an important milestone following what had been a large complex multicentered clinical trial undertaken by Soleno Therapeutics. Currently, people with PWS are being prescribed this medication in the USA, so further observations are being undertaken to monitor side effects and to establish its risks and benefits in real-life settings. The annual cost of this treatment in the USA varies with dosage but has been estimated to be an average of $466,200. An application for approval in Europe has been filed with the European Medicines Agency, with the potential for additional applications being filed globally. In the meantime, those participants with PWS outside of the USA who were in the trial are being offered the chance to continue the medication on a named patient basis.
There are other trials for the treatment of hyperphagia for people with PWS that have been undertaken, are being undertaken, are planned or under consideration. Some trials of specific treatments have ended because there has been little indication of benefit or because of serious side-effects. In the general population the use of what are called GLP-1 agonists for the treatment of diabetes mellitus and/or obesity, initially administered by injection and more recently available as a tablet, has taken off dramatically with many positive reports of significant weight loss due to reductions in food intake. But there are also concerns about side-effects and concerns about how to prevent weight gain weigh when the medication is discontinued. Experience with their use in people with PWS is limited and remains largely anecdotal with mixed reports. There are also concerns about the potential adverse impact of GLP-1 medications causing delayed gastric emptying, a phenomenon already observed in people with PWS. A recent workshop, supported by Foundation for Prader-Willi Research (FPWR) and IPWSO, has led to recommendations on how best to generate evidence regarding the safety and effectiveness of GLP-1 medications in people with PWS.
The IPWSO Research and Clinical Trials Committee monitors progress of these various trials. For families and people with PWS, treatments for hyperphagia and other aspects of the characteristic PWS features, such as anxiousness and emotional outbursts, are a priority. Effective treatments for hyperphagia also have the potential to result in improvements in other behaviours associated with the PWS phenotype. So where are we at this point in time? Having achieved approval from the FDA for one treatment for hyperphagia is undoubtedly an important milestone, as it establishes the principle that the severity of hyperphagia can be modified. We need to better understand, however, why some people with PWS respond to this specific treatment and while others do not, and to determine what we can expect from such a treatment in real-world settings where food is readily available. To what extent will food access need to be controlled? As trials of different treatments report their findings, will medications with different modes of action, or medications in combination, have similar, better, or complimentary effects? Much work remains to be done.
In a paper prepared jointly by IPWSO and FPWR, to be published shortly, we are proposing improvements in trial designs to facilitate and streamline the trial process to support more studies for this rare and complex condition. As we learn more about Vykat XR and as other treatments become available, the final hurdle will be that of cost and availability. IPWSO, National PWS Associations, and FPWR will need to help make the case for cost benefit in each country. Health systems and resources allocated to rare conditions vary considerably across the globe. Whether treatments are funded by insurance schemes or by the State, it is not going to be easy to implement changes to make treatments accessible to all persons with PWS. This is, however, a time to be optimistic.