New Phase of DCCR Trial May Support Regulatory Approval Request

Analyses revealed impacts of COVID-19, leading FDA to review additional data

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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A new phase of an open-label extension trial of DCCR for Prader-Willi Syndrome could support its application for regulatory approval.

A randomized withdrawal period in the ongoing open-label extension trial of DCCR (diazoxide choline extended-release tablets) for people with Prader-Willi syndrome (PWS) has been initiated to generate more data about the investigational treatment’s effectiveness.

The study, called C602 (NCT03714373), is evaluating the safety and effectiveness of daily DCCR in about 105 patients, all of whom are receiving the treatment and had participated in the placebo-controlled DESTINY PWS Phase 3 trial (NCT03440814).

In the withdrawal phase, participants will be randomly assigned to either continue receiving treatment or switch to a placebo for four months.

“Initiation of the randomized withdrawal period of Study C602 represents a significant milestone for our late-stage DCCR development program,” Anish Bhatnagar, MD, CEO at Soleno Therapeutics, said in a press release.

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Data are likely to support a new drug application (NDA) for regulatory approval of DCCR in the U.S, according to Soleno.

The U.S. Food and Drug Administration (FDA) had previously stated that, based on data from DESTINY, additional clinical testing would be required to support such an application, but that a new study could include DESTINY/C602 participants in order to to save time and costs. The agency later acknowledged data from a randomized withdrawal phase of C602 had the potential to serve this purpose and support an NDA application.

“As we announced previously, following interactions with the U.S. Food and Drug Administration, we have alignment that data from this portion of Study C602 have the potential to support the submission of a New Drug Application,” Bhatnagar said.

DCCR acts by blocking the release of two appetite-stimulating proteins in the brain — neuropeptide Y and agouti-related protein. These proteins are thought to drive hyperphagia, or excessive hunger, one of the main symptoms of PWS.

The treatment holds an orphan drug designation in the U.S. and Europe, as well as fast track status in the U.S., both of which aim to accelerate DCCR’s clinical development.

DESTINY evaluated DCCR’s ability to ease hyperphagia against a placebo over 13 weeks in 127 PWS patients, ages 4 and up. It failed to meet this main trial goal, however.

But further analyses revealed potential impacts of the COVID-19 pandemic on the trial, as using pre-pandemic data only showed DCCR helped curb excessive hunger and ease behavioral symptoms in patients.

In response, the FDA agreed to review additional data from DESTINY and C602 to see if they were sufficient to support an NDA, although it indicated more clinical testing would be necessary.

Collective data demonstrated DCCR led to significant reductions in hyperphagia compared with a matched group of untreated patients in the PATH for PWS natural history study (NCT03718416), with effects sustained for up to a year.

DCCR also led to caregiver-perceived improvements across several behavior domains, as well as in body composition, metabolic, and hormonal markers.

The withdrawal period of C602 will involve about 80 patients already enrolled in C602 at 17 sites in the U.S. and five in the U.K.

Usually, a randomized withdrawal phase includes only patients who were deemed treatment responders during the initial open-label extension trial. The goal is to evaluate how long it takes, if at all, for symptoms to begin flaring again. When they do, the participant will typically resume treatment.

The design of DCCR’s withdrawal phase has not been posted on the trial webpage. Soleno previously noted that top-line data for this part of the trial are expected in the first quarter of 2023.