Soleno Therapeutics has secured FDA approval for Vykat XR, marking a historic milestone as the first drug specifically approved to treat the insatiable hunger (hyperphagia) associated with Prader-Willi syndrome. The approval, announced on Wednesday, covers both adults and children aged four years and older.
Prader-Willi syndrome is a rare genetic disorder affecting an estimated 10,000 to 20,000 people in the United States. While the condition causes multiple cognitive and behavioral symptoms, the most debilitating is an unrelenting hunger that can lead to extreme obesity, metabolic complications, and even death if not carefully managed.
A Breakthrough for a Complex Disorder
Prior to this approval, Prader-Willi syndrome has been primarily managed through supportive care and human growth hormone to improve muscle mass and reduce body fat. Some physicians have prescribed the anti-seizure medication topiramate off-label to help control appetite, but no treatments specifically targeting hyperphagia had received regulatory approval.
The approval represents a significant advancement in addressing one of the most challenging aspects of the disorder. Caregivers often resort to installing locks or alarms to prevent patients from accessing food or engaging in dangerous binge eating behaviors.
"This approval addresses a critical unmet need for patients with Prader-Willi syndrome," said a spokesperson from Soleno Therapeutics. "Hyperphagia is often the most burdensome symptom for patients and their families, significantly impacting quality of life and long-term health outcomes."
An Unconventional Path to Approval
Vykat XR's journey to FDA approval followed an unusual trajectory. The drug, formerly known as DCCR, is an extended-release formulation of diazoxide, a molecule already used to treat low blood sugar. Despite failing to meet the primary endpoint in a Phase 3 trial five years ago, Soleno made a compelling case that the COVID-19 pandemic had significantly skewed the results.
The company presented evidence showing marked differences in data collected before and after March 1, 2020, and highlighted meaningful improvements in secondary outcome measures. Working collaboratively with the FDA, Soleno designed an innovative solution: adding a new component to the study where patients were randomized to either continue or discontinue Vykat treatment, then measuring hyperphagia levels over time.
This approach proved successful in September 2023, providing the efficacy data needed for the approval application. The FDA's decision acknowledges both the significant unmet need in Prader-Willi syndrome and the challenges of conducting clinical trials in rare disease populations.
Scientific Challenges and Regulatory Flexibility
The approval of Vykat XR reflects a growing recognition that rare diseases may require more flexible regulatory approaches. A 2023 editorial in the International Journal of Molecular Sciences called for greater flexibility in reviewing Prader-Willi treatments, noting that the FDA has made similar accommodations for conditions like ALS and Alzheimer's disease.
"All of these factors apply to [Prader-Willi]," the authors wrote, arguing that regulatory rigidity was causing the agency to overlook benefits that, while not primary study endpoints, were still "significant" for patients.
The scientific complexity of Prader-Willi syndrome has historically hampered drug development efforts. The condition involves multiple symptoms and complex genetics that remain incompletely understood. Since the approval of human growth hormone 25 years ago, every drug that reached Phase 3 testing had either failed or been rejected by regulators until now.
Market Impact and Future Outlook
Soleno's market value has surged past $2 billion in anticipation of this approval, despite some investor uncertainty following a delayed decision in November. Analysts at Stifel estimate the market opportunity for Vykat XR could exceed $1.5 billion annually, citing hyperphagia as the "biggest burden" for Prader-Willi patients and noting "significant patient and physician enthusiasm/awareness" for the drug.
The company has not yet disclosed Vykat XR's list price, which will be a critical factor in determining patient access. Given the chronic nature of Prader-Willi syndrome and the lack of alternative treatments, pricing and insurance coverage will significantly impact the drug's adoption and Soleno's commercial success.
This approval may also stimulate further research into Prader-Willi syndrome and other rare genetic disorders with complex manifestations. The FDA's willingness to consider alternative trial designs and endpoints could provide a blueprint for future drug development programs targeting conditions with limited treatment options.
