FDA approves DCCR, now Vykat XR, to ease hyperphagia in PWS
Soleno oral therapy expected to be available to US patients by next month
The U.S. Food and Drug Administration (FDA) has approved Soleno Therapeutics’ extended-release formulation of diazoxide choline (DCCR) for easing hyperphagia — marked by insatiable hunger — in Prader-Willi syndrome (PWS) patients ages 4 and older.
The newly authorized oral therapy will be marketed under the brand name Vykat XR. With this FDA approval, it becomes the first medication available in the U.S. to treat hyperphagia, a hallmark sign of PWS characterized by a feeling of insatiable hunger that drives food obsession, aggressive food seeking, and excessive weight gain, all beginning in childhood.
The therapy is expected to be available in the U.S. in April as oral capsules at three dose strengths: 25, 75, and 150 mg. The starting dose and target maintenance dosage are dependent on the patient’s body weight, according to its label.
“The approval of Vykat XR is a significant milestone for Soleno and, most importantly, for the PWS community who have had no options to treat the most disruptive aspect of this disease,” Anish Bhatnagar, MD, Soleno’s CEO, said in a company press release.
The decision comes about nine months after Soleno filed an application with the FDA seeking Vykat XR’s approval. That application was granted priority review, which typically shortens the review period to six months from the usual 10. Here, however, the FDA delayed its decision by three months to have time to review additional information later submitted by Soleno at the agency’s request.
Jennifer Miller, MD, a PWS expert at the University of Florida, called Vykat XR’s approval “an incredible achievement for the entire PWS community.” Miller served as a principal investigator in the therapy’s clinical development program.
“Families of people with PWS have been prisoners in their own homes because of the need to provide constant, eyes-on supervision 24/7 with access to food being completely restricted,” Miller said.
Extended-release formulation will allow all-day continued dosing
PWS is a rare, complex genetic disorder marked by several symptoms, ranging from poor growth and delayed motor skills to learning difficulties and behavioral challenges such as emotional outbursts.
Starting in childhood, patients also develop hyperphagia, which puts them at risk of obesity, high blood pressure, diabetes, and other conditions.
Taken once daily, Vykat XR activates ATP-sensitive potassium (KATP) channels, gate-like proteins that open and close in response to the amount of blood sugar, or glucose, present in the blood.
By keeping KATP channels open in a region of the brain called the hypothalamus, Vykat XR suppresses the release of two appetite-stimulating proteins that are believed to drive hyperphagia.
Its effects in the pancreas suppress the release of insulin, a hormone that helps glucose move from the bloodstream into cells. Blocking the release of insulin keeps more glucose in the blood, which increases the feeling of fullness and limits the buildup of excess fat in tissues.
As such, the therapy is expected to ease hyperphagia and associated complications.
The extended-release formulation was designed to allow the administration of Vykat XR to be done slowly in the body, over the course of a day. Starting in the stomach and continuing in the bowel, this formulation keeps the medication at steady levels in the blood with one daily dose taken by mouth.
The therapy had previously been granted orphan drug, breakthrough, and fast track designations in the U.S., as well as orphan drug status in the European Union. These designations are meant to accelerate a therapy’s clinical development and regulatory review. Orphan drug status also comes with a period of market exclusivity if a treatment is ultimately approved; in the U.S., that period is seven years.
Formerly DCCR, therapy was tested in DESTINY PWS trial, extension
The company’s regulatory application was mostly based on data from the placebo-controlled Phase 3 DESTINY PWS clinical trial (NCT03440814) and its open-label extension C602 study (NCT03714373).
The global DESTINY PWS study tested Vykat XR in 127 PWS patients, ages 4 and older. Data showed that the therapy was not superior to a placebo at reducing hyperphagia, but further analyses pointed to the COVID-19 pandemic as a potential influencing factor.
Most trial participants chose to continue on Vykat XR in the trial’s extension C602 study, in which one year of treatment was shown to significantly reduce hyperphagia and behavioral symptoms.
The therapy’s efficacy was established during C602’s four-month withdrawal period, when patients switching from Vykat XR to a placebo experienced worsening hyperphagia and put on weight relative to those continuing Vykat XR treatment.
The most commonly reported adverse events with Vykat XR were excessive hair growth, swelling, higher than normal levels of blood sugar (glucose), and rash.
This groundbreaking achievement marks a pivotal moment in the journey to provide life-changing therapies for those affected by PWS.
The FDA approval was welcomed by the Foundation for Prader-Willi Research (FPWR), which had awarded funding to support the therapy’s clinical development.
“This groundbreaking achievement marks a pivotal moment in the journey to provide life-changing therapies for those affected by PWS, and we are proud to have been a part of it,” the FPWR stated in a blog post.
The foundation will be celebrating the news with the PWS community at several locations across the U.S. over the coming month. The first event has been slated for April 19 in Omaha, Nebraska.
The developer will be providing a patient support program called Soleno One to people with PWS who are prescribed the medication. Assistance will be offered regarding insurance coverage and financial support, prescription assistance, and educational resources. Per the company, its Vykat XR copay program may help reduce out-of-pocket costs to $0 for some commercially insured patients.
Bhatnagar offered thanks to all who played a role in the therapy’s development.
“We are deeply grateful to the many individuals with PWS, their caregivers and clinical sites who participated in our trials, the advocacy groups, including FPWR and [Prader-Willi Syndrome Association USA], the advocates who have tirelessly supported the approval of Vykat XR, the FDA for a collaborative review process, and our employees who have been committed to delivering Vykat XR to those with PWS,” Bhatnagar said.
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