FDA sees no need for DCCR advisory committee meeting
Review of Prader-Willi treatment continues, Soleno says
The U.S. Food and Drug Administration (FDA) has decided that an advisory committee meeting is not needed at this point in the review process of Soleno Therapeutics‘ application seeking approval of its extended-release formulation of diazoxide choline (DCCR) to treat Prader-Willi syndrome (PWS).
Soleno announced the regulatory update in a company press release. The FDA’s review division will continue to consider the need for a meeting during its ongoing review, the company said.
FDA advisory committees, made up of independent panels of scientific experts who don’t work for the agency, review data to help the FDA make regulatory decisions. During advisory committee meetings, a therapy’s developer typically presents clinical trial data and physicians and patients share their experiences. The committee then votes on several questions regarding evidence supporting the therapy’s safety and efficacy profile, providing advice to the FDA for its final decision. Committee opinions are non-binding.
A final decision on DDCR approval is expected by Dec. 27. The FDA granted priority review to the treatment’s application, shortening the decision-making process from 10 months to six months. DCCR has also been granted orphan drug, fast track, and breakthrough designations in the U.S., as well as orphan drug status in the European Union, for PWS. These designations are aimed at speeding a treatment’s clinical development and regulatory review.
PWS is a rare genetic disorder that occurs in approximately one in 15,000 live births, according to the Prader-Willi Syndrome Association USA. The condition is marked by symptoms including hyperphagia, an overwhelming and constant hunger; developmental delays; cognitive disabilities; and behavioral issues.
DCCR would be first hyperphagia therapy
A survey by the Foundation for Prader-Willi Research revealed that 96.5% of caregivers and parents ranked hyperphagia as either the most important or a very important symptom to be addressed by a new therapy. The increased appetite causes patients to obsess over food, leading to excessive eating, weight gain, and health problems like diabetes and cardiovascular disease.
DCCR would be the first approved therapy to treat these symptoms, according to Soleno.
The therapy is a once-daily extended-release tablet of diazoxide choline that’s designed to address hyperphagia and other symptoms of PWS. It works by activating specific gate-like proteins in the brain and pancreas, a mechanism thought to reduce appetite, increase feelings of satiety, and reduce fat buildup.
While the base compound, diazoxide, has been used for decades in some rare diseases, DCCR has been specially formulated for PWS, the company said.
The development program for DCCR includes five Phase 1 clinical trials in healthy volunteers; three Phase 2 trials, one specifically involving people with PWS; and two Phase 3 studies in patients.
Results from the placebo-controlled Phase 3 DESTINY PWS trial (NCT03440814), which involved 127 patients ages 4 and older, suggested that DCCR may help alleviate hyperphagia, aggressive behaviors, and other metabolic issues associated with PWS.
However, differences between the DCCR and placebo groups in terms of hyperphagia changes did not reach statistical significance, failing to meet the trial’s main goal. Some evidence suggested that results may have been influenced by the COVID-19 pandemic.
In response to the FDA’s request for more data, Soleno implemented a four-month withdrawal period in DESTINY’s open-label extension study C602 (NCT03714373), in which patients either switched to a placebo or continued their daily treatment with DCCR.
Results from this period showed that those who switched from DCCR to a placebo experienced worsening hyperphagia and weight gain, data that helps to support the regulatory application.
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