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Soleno Therapeutics Prader-Willi Therapy Fails in Phase 3 Study

June 9, 2020

Soleno Therapeutics said top line results showed its experimental diazoxide choline controlled release tablets failed to meet the primary endpoints in a phase 3 study in Prader-Willi syndrome.

Photo: Anish Bhatnagar, CEO of Soleno Therapeutics

Prader-Willi syndrome (PSW) in characterized by hyperphagia, a chronic feeling of insatiable hunger that severely diminishes the quality of life for PWS patients and their families. Additional characteristics of PWS include behavioral problems, cognitive disabilities, low muscle tone, short stature (when not treated with growth hormone), the accumulation of excess body fat, developmental delays, and incomplete sexual development. Hyperphagia can lead to significant stomach rupture, obesity, diabetes, and cardiovascular disease. It can also lead to accidental death as a result of choking, or food seeking behavior. There are currently no approved therapies to treat the hyperphagia/appetite, metabolic, cognitive function, or behavioral aspects of the disorder.

Diazoxide choline controlled-release tablet (DCCR) is a novel, proprietary extended-release, crystalline salt formulation of diazoxide, which is administered once-daily. The parent molecule, diazoxide, has been used for decades in thousands of patients in a few rare diseases in neonates, infants, children, and adults, but has not been approved for use in Prader-Willi syndrome. Diazoxide choline has received Orphan Drug designation for the treatment of PWS in the United States and European Union, and Fast Track designation in the United States.

The phase 3 Destiny PWS /C601 study failed to meet its primary endpoint of change from baseline in hyperphagia. The change was measured by the total score of a Hyperphagia Questionnaire for Clinical Trials. An improvement in HQ-CT is represented by a decrease in the score. The mean change from baseline for DCCR was -5.94 and for placebo was -4.27. Soleno, however, said in a prespecified subgroup of subjects with more severe hyperphagia, the mean change from baseline for DCCR was -9.67 and for placebo was -4.26.  

Significant changes were observed in two of three key secondary endpoints from baseline to week 13 in subjects receiving DCCR as compared to placebo. This includes improvement in Clinical Global Impression of Improvement score as assessed by the investigator and in reduction of measured body fat mass.

A total of 115 subjects were enrolled into C602, an ongoing open-label, safety extension study of DCCR in PWS patients completing C601, and more than 90 percent of them are continuing to be treated at this time. An interim analysis of subjects who have completed three months of treatment on C602 shows continuing improvements in hyperphagia.

DCCR subjects from C601 at six months of treatment demonstrated a reduction in hyperphagia score of -11.7 (-48 percent) and placebo subjects from C601 who switched to DCCR showed a similar change following three months of treatment in C602.

Behaviors related to PWS are measured using a PWS Profile Questionnaire, which consists of caregiver responses to questions in six domains: aggressive behaviors, anxiety, rigidity-irritability, compulsivity, depression, and disordered thinking. Improvements in most domains were seen in C601 with DCCR treatment. In subjects from C601 treated with DCCR, each domain showed further improvement in C602. Placebo subjects from C601 who switched to DCCR showed a similar change following three months of treatment in C602.

“While we are disappointed to have not achieved statistical significance on the study’s primary endpoint, we are excited by the results observed in those subjects with severe hyperphagia, as well as the changes in body composition and behavioral endpoints,” said Anish Bhatnagar, CEO of Soleno Therapeutics. “Based on these data, we will continue treatment of patients in C602. We are continuing to evaluate the data from C601 and C602 and plan to meet with regulatory authorities to determine next steps.

Author: Rare Daily Staff

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