By Marcin Miszkowski
Now we have knocked on the door and entered 2023, this is an opportunity to look back and reflect on some of the crucial research that emerged in 2022 to better understand and treat PWS. Fundraising to support research is critical to continue the exciting work that has been happening behind the scenes in an attempt to ease some of the complexities that make up the syndrome. As the world reels from COVID-19, 2023 will see new challenges facing researchers, medical professionals, fundraisers and donors.
The year began with news that the FDA called for an additional trial of Soleno’s diazoxide choline controlled release (DCCR) tablets, before considering approval for PWS treatment. The department stated that there may be the possibility of using people already enrolled in the DESTINY PWS Phase 3 trial, which would “significantly reduce the time and cost to obtain the necessary data,” said Soleno’s MD, Anish Bhatnagar. In May, data was released showing that DCCR safely led to reductions in excessive hunger and disease-related behaviours. The positive news that DCCR has the potential to be an effective tool in managing hyperphagia came as encouraging news to the PWS community. The initial DESTINY trial did not provide conclusive results that DCCR was effective at reducing the impact of hyperphagia.
However, additional analysis suggested that COVID-19 had a significant impact on the trial and an open extension was granted to continue testing, yielding positive results.
DCCR works by inhibiting appetite-stimulating proteins from the brain, which are thought to drive hyperphagia. DCCRs use during the trial greatly reduced the hyperphagia compared to the control group that received a placebo. Caregiver questionnaires further advocated its use by indicating a reduction in anxiety, aggression, compulsion and a number of other PWS symptoms. These findings have been passed to the FDA for further consideration in approving DCCR for use in people with PWS. Most recently, a study as part of the DESTINY Phase 3 Trial has started, looking at the effectiveness of the drug by withdrawing the treatment in a random selection of patients. Soleno, the manufacturer, believes the study will produce positive results to support a new drug application as part of the approval process with the FDA. Read more about the latest trial here.
Supporting PWS research is crucial to allow existing trials to continue and new ones to gain the traction needed to have data produced and submitted for approval from the FDA and other drug agencies around the world. In January, Radius Health announced details of its Cannabinol-based RAD011 program, and in July, details were published of the first person being assigned to the dosing group of the pivotal Phase 2/3 SCOUT 015 trial, which would test the efficacy of RAD011. The news was met with much excitement from members of the PWS community. Ongoing recruitment across the US and other international sites is critical to the development of RAD011, which if approved, has the potential to have significant positive impacts on managing hyperphagia. We await results and news from the trial which is due to end in 2024. Further information is available at this link.
In less positive news, Saniona, the maker of Tesomet, announced in April that it had to pause the Phase 2b trial due to funding. The organisation announced that it had to reprioritise and restructure its organisation, leading to a reduction of the workforce by approximately 30%. At present, there is no news to suggest that trials will continue, which is disappointing news as initial indications suggested that Tesomet had the potential to be administered as a partial treatment for PWS. Tesomet works by preventing the brain from reabsorbing certain neurotransmitters: serotonin, dopamine and noradrenaline. By preventing this reabsorption, the levels of these neurotransmitters in the brain remains high and as a consequence, reduces food cravings, appetite and increases calorie burn. Click here for details and a link to Saniona’s website.
There is much to be said about the importance and significance of drug trials in developing treatments not just for PWS, but a wide range of other conditions and diseases. It is important to remember that without additional research being conducted into the causes, impacts and traits of conditions such as PWS, drug trials would lack the evidence to develop therapies. Throughout the year, a wealth of research papers have emerged that look at and shed light into the intricacies of PWS to allow pharmaceutical developers, caregivers and the general public a better understanding of PWS. In May and July, further evidence emerged of the importance of starting Growth Hormone (GH) early and how GH positively impacts those with PWS. This latest evidence adds to existing data that starting treatment of GH before 1 year old encourages improved development of physical, metabolic and cognitive characteristics in people with PWS.
The encouraging news that Liraglutide was showing to reduce the need for excessive eating was another positive indication of the progress of PWS research during 2022. Understanding of the syndrome has also deepened through the development and implementation of the Prader-WIlli Anxiety and Distress Questionnaire (PADQ). The PADQ is an assessment tool used to measure anxiety and distress in people with PWS, asking questions that revolve around some of the unique anxieties of PWS, such as diet management and routine. This caregiver administered questionnaire provides data for researchers and pharmaceutical manufacturers by sharing observations of anxiety and distress over a period of time. The PADQ has proved to be consistent and reliable in measuring anxiety and distress on either side of drug trials to provide secondary outcomes useful in treatment development.
As 2023 gains momentum, there seems to be a sense of optimism as researchers continue to find and develop treatments for PWS. There is positive data coming from drug trials, a deepening understanding of how the syndrome develops and new strategies to help manage and understand the distress that comes about with the syndrome. Ensuring this research continues is made possible by fundraisers and groups of volunteers who facilitate and manage websites, organise charity events, write blogs and generally advocate for this incredible community.