Written by Pavan Reddy (Biomedical Engineer) and Pragati Ekamalli (B.Pharm)
Reviewed and Fact Checked by Vikas Londhe M.Pharm (Pharmacology)
Introduction
The U.S. Food and Drug Administration (FDA) have recently approved VykaT XR (diazoxide choline extended-release) for the treatment of hyperphagia an insatiable hunger and food-seeking behaviour—in patients with Prader-Willi Syndrome (PWS). This marks a significant milestone in addressing one of the most challenging and life-threatening aspects of PWS.
Understanding Prader-Willi Syndrome and Hyperphagia
Prader-Willi Syndrome is a rare genetic disorder characterized by hypotonia, developmental delays, behavioural challenges, and endocrine abnormalities. One of the most debilitating symptoms is hyperphagia, an extreme and unrelenting hunger that can lead to severe obesity, diabetes, and life-threatening complications if not carefully managed.
Hyperphagia in Prader-Willi Syndrome (PWS) is a hallmark symptom and one of the most challenging aspects of the condition to manage.
Hyperphagia refers to an abnormally increased appetite for and consumption of food. In PWS, this goes beyond typical overeating — it’s a compulsive drive to eat that often leads to life-threatening obesity if not carefully managed.
Prader-Willi Syndrome is a complex genetic disorder caused by the loss of function of specific genes on chromosome 15 (most often from the paternal side). One of the primary areas affected is the hypothalamus, the brain region responsible for regulating hunger and satiety.
Because of this hypothalamic dysfunction:
Individuals with PWS don’t receive normal signals of fullness.
Ghrelin, the “hunger hormone,” is often found at abnormally high levels.
This creates a constant feeling of hunger, regardless of how much food is consumed.
PWS-related eating behaviour typically progresses in stages:
Infancy – Poor muscle tone (hypotonia) and feeding difficulties, often requiring tube feeding.
Early Childhood (2–4 years) – Weight gain begins without an apparent increase in food intake.
Later Childhood – An insatiable appetite emerges; the drive to eat intensifies, often leading to food-seeking behaviors, hoarding, and even food theft.
Until now, treatment options for hyperphagia have been limited tostrict dietary supervision, behavioural therapy, and growth hormone therapy (which help with some symptoms but do not directly address hyperphagia).
VykaT XR offers the first FDA-approved pharmacological treatment specifically targeting this symptom.
What is VykaT XR (Diazoxide Choline)?
Diazoxide choline is a salt form of diazoxide, a medication that has been around for decades, primarily used to treat conditions like hypoglycemia (low blood sugar) due to its ability to inhibit insulin secretion and hypertension (high blood pressure). The choline salt form is designed to potentially improve the bioavailability and tolerability of diazoxide, especially in oral formulations.
VykaT XR is an extended-release formulation of diazoxide choline, a modified version of diazoxide.
Key Benefits of VykaT XR
Reduces excessive hunger by acting on brain pathways involved in appetite regulation.
Extended-release formulation allows for once-daily dosing, improving compliance.
Potential to improve quality of life by reducing food-related anxiety and obsessive behaviors.
Clinical Trials and Efficacy
The approval of VykaT XR was based on data from Phase 3 clinical trials demonstrating its effectiveness in reducing hyperphagia symptoms. Key findings included
The C602-RWP (Randomized Withdrawal Period) was a phase of the C602 clinical study evaluating the efficacy and safety of Diazoxide Choline Extended-Release (DCCR) tablets for treating Prader-Willi Syndrome (PWS). This phase was specifically assessed the impact of discontinuing DCCR on hyperphagia-related behaviors in individuals with PWS.
Study design includes 77 individual participants with PWS who had previously been enrolled in the C602 open-label extension study and had received DCCR treatment for two to four years. Participants were randomized in a 1:1 ratio to either continue DCCR treatment or switch to a placebo for duration of 16 weeks. Primary Endpoint include Change from baseline in hyperphagia-related behaviors, measured using the Hyperphagia Questionnaire for Clinical Trials (HQ-CT).
Key Findings of the trial in hyperphagia Assessment at week 16, participants who switched to placebo showed a significant worsening in hyperphagia-related behaviors, with an increase of 5.0 points in the HQ-CT total score compared to those who continued DCCR treatment
Secondary endpoints, including the Clinical Global Impression of Severity (CGI-S) and Clinical Global Impression of Improvement (CGI-I), indicated trends toward worsening conditions in the placebo group compared to the DCCR group.
DCCR was generally well-tolerated, with no new or unexpected safety signals reported during the randomized withdrawal period.
These results suggest that continuous treatment with DCCR may be beneficial in managing hyperphagia in individuals with PWS, and discontinuation could lead to a significant worsening of symptoms. Based on these findings, Soleno Therapeutics planned to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA).
Implications for Patients and Families
For individuals with PWS and their caregivers, VykaT XR offers new hope in managing a symptom that has long been a major source of distress. Many caregivers view VykaT XR as a long-awaited option that addresses one of the most difficult aspects of PWS.
Patient advocacy groups Prader-Willi Syndrome Association USA have shared cautiously optimistic statements, emphasizing the potential impact on family dynamics, independence, and safety. However Community discussions indicate concerns about insurance coverage, cost, and provider awareness.
Conclusion
The FDA’s approval of VykaT XR represents a groundbreaking advancement in the treatment of Prader-Willi Syndrome. While ongoing research will further define its long-term benefits and safety profile, this therapy provides a much-needed tool in managing hyperphagia a symptom that profoundly impacts the lives of those with PWS.
Patients and healthcare providers are encouraged to discuss VykaT XR as part of a comprehensive PWS management plan, which should continue to include nutritional support, behavioural interventions, and endocrine care.
For now, VykaT XR stands as a landmark therapy, offering new possibilities for individuals and families affected by Prader-Willi Syndrome.
References
- US FDA approval of VykaT XR, Soleno Therapeutics, 26 March 2025, available from https://investors.soleno.life/static-files/9e8f0f73-ea3b-47fe-8c8e-fbd276a31333
- Soleno therapeutics announces U.S. FDA approval of VykaT XR to treat hyperphagia in Prader-Willi Syndrome, Soleno Therapeutics, 26 March 2025, available from https://investors.soleno.life/news-releases/news-release-details/soleno-therapeutics-announces-us-fda-approval-vykattm-xr-treat
- Driscoll DJ, Miller JL, Cassidy SB. Prader-Willi Syndrome. 1998 Oct 6 [Updated 2024 Dec 5]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1330/
4. Prader-Willi Syndrome, Foundation for Prader Willi Research, available from https://www.fpwr.org/what-is-prader-willi-syndrome#definition
- Rahman QFA, Jufri NF, Hamid A. Hyperphagia in Prader-Willi syndrome with obesity: From development to pharmacological treatment. Intractable Rare Dis Res. 2023 Feb; 12(1):5-12. Doi: 10.5582/irdr.2022.01127. PMID: 36873672; PMCID: PMC9976092.
- S.A. Bellis, I. Kuhn, S. Adams, L. Mullarkey, A. Holland, The consequences of hyperphagia in people with Prader-Willi Syndrome: A systematic review of studies of morbidity and mortality, European Journal of Medical Genetics, Volume 65, Issue 1, 2022,104379, https://doi.org/10.1016/j.ejmg.2021.104379
- Holsen LM, Zarcone JR, Brooks WM, Butler MG, Thompson TI, Ahluwalia JS, Nollen NL, Savage CR. Neural mechanisms underlying hyperphagia in Prader-Willi syndrome. Obesity (Silver Spring). 2006 Jun;14(6):1028-37. Doi: 10.1038/oby.2006.118. PMID: 16861608; PMCID: PMC1535344
- Miller JL, Gevers E, Bridges N, et al, Diazoxide Choline Extended-Release Tablet in People With Prader-Willi Syndrome: A Double-Blind, Placebo-Controlled Trial. J Clin Endocrinol Metab. 2023 Jun 16;108(7):1676-1685. Doi: 10.1210/clinem/dgad014. PMID: 36639249; PMCID: PMC10271219.
9. Vykat XR FDA Approval History, Drugs.com, available from https://www.drugs.com/history/vykat-xr.html
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