In Interviews, PWS Caregivers Find DCCR Helps to Ease Troubling Behaviors
In interviews, most caregivers of people with Prader-Willi syndrome (PWS) reported an easing in patients’ behavioral symptoms after 13 or more weeks of treatment with diazoxide choline controlled release (DCCR) tablets in a Phase 3 trial or its ongoing extension study.
Interviews were given to 48 caregivers of enrolled patients after the 13-week main trial concluded and failed to meet its main goal. Subsequent analyses suggested that the COVID-19 pandemic, which erupted during the trial, affected its outcomes, and the interviews help to establish “a more complete view of therapeutic impact,” researchers wrote.
These preliminary findings were presented in the poster “Application of a semi-automated framework to characterize individual experiences with DCCR in Prader-Willi syndrome (PWS) – A Preliminary Analysis,” at the Pediatric Academic Societies 2021 Virtual Annual Meeting, running in two parts from April 30 to June 4.
Developed by Soleno Therapeutics, DCCR is designed to suppress the release of two appetite-stimulating proteins in the brain — neuropeptide Y and agouti-related protein — which are believed to drive hyperphagia. DCCR is given daily and is an extended release version of diazoxide, an approved medication for low blood sugar.
Soleno submitted an updated analysis from its DESTINY PWS Phase 3 clinical trial (NCT03440814) to the U.S. Food and Drug Administration (FDA) in February, showing that DCCR helped to curb hyperphagia (excessive hunger) and ease behavioral symptoms in PWS patients.
That analysis focused on data covering its 127 patients, collected before COVID-19 was declared a national emergency in the U.S.
Previous top-line trial data, released in June 2020, found the treatment failed to meet the study’s main goal of significantly reducing hyperphagia, assessed through a caregiver questionnaire. Results also showed no significant benefits over a placebo on caregiver-reported clinical improvements.
Differences between pre-pandemic and overall trial data led investigators to suspect that COVID-19 had a direct and significant impact on top-line study results.
FDA officials, however, decided that an additional trial would be required to support a future request that DCCR tablets be approved for PWS, despite the opposition of advocacy groups concerned at the delay a new clinical study would bring.
The DESTINY PWS open-label extension (NCT03714373) is ongoing at clinical sites across the U.S. and the U.K. Its main goal is to assess the long-term safety of DCCR tablets, with all participants receiving the therapy for up to three years.
Caregiver interviews were part of its newly presented outcomes data. Casimir, a rare disease research organization, conducted the interviews at different trial times, and after at least 13 weeks (over three months) of the treatment’s use.
A total of 39 behavior patterns, belonging to seven major domains — food-seeking, mealtime, daily life, school and public behaviors; family dynamics, and somatics (physical symptoms) — were identified. The most commonly reported behaviors were linked with food-seeking (100%), mealtime (98%), and daily life (98%).
Nearly half (48%) of those interviewed reported a positive change in at least 50% of these behavioral symptoms with DCCR treatment. Improvements in 25% or more of the symptoms were reported by 71% of the 48 caregivers. Most (83%) reported beneficial changes in one or more behaviors, with 6% reporting more than one negative change.
“In complex disorders like PWS, it is important for clinical research to capture variation in individual patient experiences, to form a more complete view of therapeutic impact. Using such a framework, it was shown that participants in the DCCR Phase 3 program experienced several positive behavioral outcomes associated with treatment,” the scientists wrote.
“These important data provide critical insights into the long-term behavioral responses to DCCR in PWS, and support a more complete view of this promising investigational drug’s therapeutic benefits,” Anish Bhatnagar, MD, Soleno’s CEO, said in a press release.
“The growing body of clinical evidence continues to indicate that DCCR has the potential to address the significant need for a safe and effective treatment for individuals with PWS,” Bhatnagar added.
Interview outcomes were analyzed by Folia Health using a combination of natural language processing (NLP) techniques and qualitative analysis. NLP uses artificial intelligence so that computers are able to read, understand and derive meaning from human language.
“It is exciting to see the utilization of natural language processing for the first time to determine caregiver sentiment in patients with PWS. NLP and other artificial intelligence techniques are the future of qualitative data analysis and can be particularly useful in rare-disease research,” said Deepan Singh, MD, at the Maimonides Medical Center in New York.
“Behavioral abnormalities in PWS are heterogenous and very difficult to treat. I am encouraged by DCCR’s potential to impact these intractable problematic behaviors in individuals with PWS,” Singh said.