Running for Research Supports Trial of DCCR in Early-phase PWS

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by Lindsey Shapiro PhD |

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Soleno Therapeutics has announced that its diazoxide choline controlled release (DCCR) tablets will be evaluated in a clinical trial for people with early-phase Prader-Willi Syndrome (PWS), which will be funded by Running for Research – Prader-Willi Syndrome, an ongoing fundraiser to benefit PWS research operated by the University of Florida.

DCCR will be evaluated in approximately 40 PWS patients who do not yet have hyperphagia, or excessive hunger — a hallmark PWS symptom. The trial will be conducted at four institutions: the University of Florida, University of Louisville, University of Minnesota, and Nationwide Children’s Hospital in Columbus, Ohio.

“This study will evaluate the impact of DCCR on patients with PWS before they develop hyperphagia and evaluate its potential to slow or prevent progression of PWS,” Jennifer L. Miller, MD, a University of Florida professor and the study’s principal investigator, said in a press release.

The trial will evaluate the effects of DCCR on body composition, insulin resistance, appetite, sleep, and other metabolic parameters. No placebo will be given, so potential participants who do not want to be on an investigational therapy will serve as the control group.

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For both groups, the study will involve three in-person visits over the first year, and then annual visits thereafter. The dose of DCCR will be increased slowly to the maximum dose (4 mg/kg per day) that was shown to be clinically effective in previous trials.

“We are excited to further evaluate this promising product candidate in the clinic through this study,” Miller added.

Hyperphagia usually emerges in childhood, eventually leading to obesity and other health complications, like type 2 diabetes, in people with PWS.

“Patients with PWS progress through several nutritional phases before they reach Nutritional Phase 3, characterized by hyperphagia, as well as other behavioral issues and significant metabolic abnormalities,” Miller said.

DCCR is a once-daily oral therapy designed to block the release of neuropeptide Y and agouti-related protein, two appetite-stimulating proteins in the brain that are thought to drive hyperphagia.

Soleno hopes that early treatment with DCCR in PWS patients could prevent hyperphagia from emerging.

Previous trials have evaluated DCCR in PWS patients with hyperphagia.

Data from an open-label Phase 1/2 trial (NCT02034071) showed that DCCR treatment led to sustained decreases in hyperphagia, body fat, and aggressive and violent behaviors in PWS patients compared with a placebo.

The Phase 3 DESTINY PWS trial (NCT03440814), however, failed to meet its primary goal of easing hyperphagia, leading the U.S. Food and Drug Administration (FDA) to request an additional clinical trial prior to regulatory approval.

A later analysis revealed that the COVID-19 pandemic may have significantly influenced the results of the trial, prompting the FDA to agree to review additional data from DESTINY PWS and its open-label extension study (NCT03714373), called C602, which is testing the one-year efficacy of DCCR for up to three years.

Initial results from C602 indicated that the treatment lessened hyperphagia and behavioral symptoms, in addition to improving hormonal and metabolic profiles.

The FDA also recently agreed that while it awaits more data, any new clinical trials can include current DESTINY participants to reduce time and cost. Soleno noted that it has since submitted a proposal to the FDA for a study involving C602 participants.

“We believe the data generated to date from the ongoing clinical program suggest the potential of DCCR as a treatment option for early phase PWS patients,” said Anish Bhatnagar, MD, Soleno’s CEO. “Soleno is pleased to provide DCCR for this study to evaluate DCCR in pre-hyperphagic patients to test this hypothesis. We are grateful for the support from Dr. Miller, [Running for Research] and the entire PWS community as we continue the development of DCCR for PWS.”

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This year’s Running for Research campaign has raised more than $643,000 for PWS research.

“Running for Research – Prader-Willi Syndrome was founded for the purpose of funding important scientific research,” said Kelly Shad Guillou, the fundraiser’s co-founder.

“We have vastly exceeded our funding goal for this clinical trial, more than quadrupling our original target,” she added. “This is by far the largest amount we have raised to date on behalf of any specific research project. We are thrilled with our success and believe it is indicative, in large part, of the high level of enthusiasm from the PWS community for DCCR and this study.”