Development Program for DCCR in PWS
In a Phase 2 study of DCCR in individuals with genetically-confirmed PWS, the administration of DCCR resulted in significant reductions in hyperphagia and fat mass, increases in lean body mass, and reductions in aggressive, threatening, and destructive behaviors.
Based on these data, Soleno initiated DESTINY PWS, a 13-week randomized, double-blind placebo-controlled Phase 3 study in 127 individuals with a genetically confirmed diagnosis of PWS aged four years and older with hyperphagia in the U.S. and U.K.
While DESTINY PWS did not show a statistically significant change in hyperphagia in the DCCR group compared to the placebo group, the DCCR group showed nominally significant:
- decreases in fat mass
- overall improvement in the PWS as rated by the Investigator
- improvements in hyperphagia in those with more severe hyperphagia at baseline.
Data generated prior to the onset of the COVID-19 pandemic showed improvements in the DCCR group compared to the placebo group in hyperphagia, overall PWS rated by the Investigator and the Caregiver, body fat mass, and in several PWS-associated behavioral endpoints including aggressive behaviors, anxiety, compulsivity and rigidity/irritability.
More than 95% of patients who completed DESTINY PWS went on to receive DCCR in the open-label extension period of Study C602.
For a more complete summary of safety and efficacy results, view C601 publication
“These results further emphasize the potential for DCCR to be a meaningful treatment that improves multiple key symptoms of PWS, which has significant implications for patients and families struggling to manage this devastating disease.”
Dr. Eric Felner
Emory University School of Medicine
C602 Open-Label Extension Period
Participants who completed the DESTINY PWS study enrolled in an open-label extension period. Participants who continued in the study have completed at least 2 years of DCCR administration.
An interim analysis was conducted after all eligible participants received open-label DCCR for at least 1 year and showed:
- Statistically significant decreases from baseline hyperphagia score
- Larger average decreases in hyperphagia in those who had more severe hyperphagia at baseline
- Statistically significant decreases from baseline in scores for aggressive behavior, anxiety, compulsivity, and irritability / rigidity
- Mean overall decreases in disease severity ratings by the Investigator and the caregiver
- Statistically significant decreases in mean HOMA-IR levels, a measure of insulin resistance.
For a summary of interim safety results, view long term safety poster (pdf)
C610 Comparison to Natural History
PATH for PWS is a natural history study being conducted by the Foundation for Prader-Willi Research (FPWR). The purpose of the study is to characterize the natural history of PWS with respect to hyperphagia and other behaviors. A cohort from PATH for PWS with similar disease profiles as individuals enrolled in DESTINY PWS were selected and compared to the results from DESTINY PWS and C602.
Compared to PATH for PWS, participants who were administered DCCR showed:
- Significant improvements in hyperphagia
- Significant reductions in a range of PWS-related behaviors, including aggressive behaviors, anxiety, compulsivity, and rigidity/irritability.
Safety
DCCR showed no new safety signals compared to use of diazoxide to treat very rare genetic conditions characterized by hypoglycemia due to hyperinsulinism, collectively estimated at 100,000 person-years (i.e., estimated number of patients who have used diazoxide multiplied by the average duration of use) globally.
The majority of adverse events experienced were mild (grade 1), with no grade 4 or higher events. The most common treatment emergent adverse events (TEAEs) were hypertrichosis (excess hair growth), peripheral edema, and hyperglycemia.
To see details of the safety of DCCR from the C602 interim analysis view long term safety poster, view long term safety poster (pdf)
Leadership in genetic profiling
Research in genetic profiling at Soleno has also deepened understanding of the genetic factors associated with the response to treatment with KATP channel activators in PWS that may also allow identification of individuals with other rare genetic disorders who may benefit from treatment with DCCR.
“PWS is a spectrum disorder, with symptoms varying in severity and occurrence. However, what is consistent within this community is the desperate need for effective therapeutic options to address the most burdensome aspects of this disorder, including hyperphagia and behavioral issues.”
Neil M. Cowen, PhD, MBA
Senior Vice President of Drug Development
Developing novel therapeutics for the treatment of rare diseases