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Return of Results: Destiny-PWS by Soleno Therapeutics [2020 CONFERENCE VIDEO]

In this video, promising results from the Phase 3 clinical trial of DCCR are described by the CEO of Soleno Therapeutics and researcher Dr. Jennifer Miller.

In this hour-long video, the CEO of Soleno Therapeutics and researcher Dr. Jennifer Miller go into detail on the design and results of the DCCR phase 3 clinical trial. The session also covers next steps for making the drug available to treat PWS, discussed by Larry Bauer, who worked in the rare diseases program at the FDA. The session includes questions from the audience and answers from panelists at the 2020 Virtual PWS Family Conference.

Click below to watch the video. If you're short on time, scroll down for timestamps to find the portions you're most interested in.


Presentation Summary With Timestamps

0:30 Susan Hedstrom introduces Anish Bhatnagar, CEO of Soleno Therapeutics.

  • Diazoxide Choline Extended Release (DCCR) in PWS is a study called the DESTINY PWS study. 

1:46 Natural History Study: Post Prandial Insulin

  • Insulin increases dramatically in PWS patients, especially after eating. 
  • DCCR is a tablet form of extended release diazoxide choline, which isn’t approved for PWS. Taken once a day, it can help maintain stable levels in the body.
  • Diazoxide is only indicated for hyperinsulinism. Hard to dose because there are problems with dose uniformity.

5:30 How does DCCR work in the body?

  • DCCR acts on a channel called the ATP dependent potassium channel, or KTP channel. 
  • In the hypothalamus: it reduces the levels of neuropeptides that drive hunger and food seeking, resulting in improved food related behaviors.
  • In the vagal nerve, it inhibits neurons that result in lower insulin levels, improved insulin sensitivity, increased satiety and reduced appetite.
  • In fat tissue, it reduces the disposition of new fat and increased use of fat for energy, reducing fat mass.
  • In the pancreas, it reduces post-meal insulin levels resulting in reduced deposition of fat, and improved insulin and leptin resistance.

6:29 DCCR: Early Phase Data

  • Prior to the first study of DCCR in PWS, there had been 5 Phase I studies and 2 Phase II studies.
  • The pilot study that was conducted in 13 PWS subjects ages 10-22, the results were a significant reduction in hyperphagia, loss of body fat, increased lean body mass and reductions in aggressive behaviors.
  • Soleno designed two separate studies: the C601 or DESTINY PWS Phase III study and the C602 open-label safety extension study.
  • The first study, C601, enrolled a total of 158 eligible participants, and they were randomized to receive the DCCR or the placebo. Out of the total, 115 participants are currently in the C602.
  • The enrolled participants had genetically confirmed PWS and moderate to severe hyperphagia. 

10:14 Dr. Jennifer Miller continues with presentation of the Results of Phase III Clinical Trial

  • The baseline characteristics of the participants were very similar across the two different randomized groups.
  • The primary endpoint was change in hyperphagia in week 13, but there was no statistical significance between the placebo and drug groups.

12:19 HQ-CT score: Primary Endpoint 

  • The higher hyperphagia score the patients had at baseline, the more response their bodies had to DCCR. 
  • The more significant change in hyperphagia scores, the more likely it is to have been on DCCR.
  • Out of the nine questions that indicate a higher HQ-CT score, the DCCR exceed placebo in responsiveness to reduce the score.

15:48 Key Secondary Endpoints

  • The CGI-I and CGI-C scores, as well as DXA scan were considered key secondary endpoints. 
  • The investigators’ CGI-I score and DXA data had statistically significant responses on DCCR vs placebo at the end of the study.
  • The CGI-C scores, scored by the caregiver, did not show any statistical significance, probably because the drug was slowly titrated.

19:53 Changes in Body Composition

  • In DXA data, there was a significant decline in fat mass in participants who received DCCR.

21:45 Hyperphagia in PWS

  • As children with PWS naturally move from nutritional phase 2a to 2b, and from 2b to 3, their leptin and insulin levels rise significantly and typically stay  .
  • On DCCR, the results show they had changes in Leptin and Adiponectin (another adipose-related hormone, which is cardioprotective)
  • The fasting insulin change from baseline decreased significantly, as well as HOMA-IR, a measurement of insulin resistance that takes into account blood sugars and insulin levels.
  • Ghrelin levels show improvements for participants who took DCCR  

24:33 Transition into C602

  • All subjects who had completed 13 weeks of open-label treatment were given the choice to continue participating in C602.
  • Participants who were given DCCR and continue on D602, continue to show improvements, including a decline in hyperphagia score.

26:13 Behavioral Changes from C601 baseline

  • Aggressive behaviors, anxiety, rigidity, irritability indicators all decreased in participants who received DCCR.

31:19 C601 Safety Data

  • Hypertrichosis, or increased body hair growth is a known side effect from DCCR, as well as lower leg edema and hyperglycemia or high blood sugar.
  • Participants who were on DCCR experienced more adverse events than the placebo population, and those with serious adverse events were indicated to discontinue taking the drug.
  • Most events were Grade 1 in severity, and there were no Grade 4 or higher events reported in this study.
  • There were no suspected unexpected serious adverse reactions (SUSARs) related to DCCR.

36:45 Q&A session moderated by Susan Hedstrom

41:50 Larry Bauer presents 

  • Having worked previously in the rare diseases program in the FDA, he worked with patient advocacy groups, and one of his goals was to get patients to be more engaged in the drug development process.

43:00 Overview of FDA drug review 

  • Drug development happens in different phases.
  • In the preclinical or exploratory phase, it’s studied in test tubes and animals.
  • Phase I is meant to determine safety and dose in healthy volunteers.
  • Phase II is when the drug is tested on patients with the disease under study. Safety is tested in small numbers of patients with the disease to get safety data.
  • In Phase III studies, it’s given to a larger number of patients to confirm its effectiveness, side effects and safety. 
  • Phase IV is called post marketing, where the drug is approved and available, and continues to be monitored for safety and side effects.

45:07 Overview of FDA drug review 

  • Drug submission to the FDA is the next step, where the process is handed to the FDA to make a decision on the drug approval.
  • There are teams of reviewers within the FDA who review the chemistry, manufacturing, non-clinical data and clinical data, and then they do their own statistical analysis and conduct a benefit/risk evaluation.
  • The process takes from 6 to 10 months, approximately.
  • Once a new drug application is submitted to the FDA and is under review, the only place for patients to contribute to the process is if there is an Advisory Committee meeting.
  • The FDA reviews all data submitted and considers the “totality of evidence” to decide whether to approve a new drug or not, considering the risks.

49:17 History of Patient Engagement 

  • Historically, the patient voice wasn’t included in the drug development process.
  • In the 1980s, AIDS activists demonstrated and got a seat at the table to give input into said process.
  • Patients and caregivers can give a broader perspective of symptoms and can help inform the study design and tolerable risks.

50:55 How to get involved 

  • Participate in the Global PWS Registry, which helps map out the natural history of PWS.
  • Participate in Clinical Studies
  • Help scientists, clinicians and drug developers understand what is important to you.
  • Educate others around you: family, friends, physicians, and community, while supporting other PWS families in your community.

52:18 How FPWR supports patients and caregivers

  • Dr. Theresa Strong, director of research at FPWR, is a member of the FDA Patient Engagement Collaborative, which provides input on patient engagement.
  • Interacting with the FDA through the Clinical Trial Consortium Workshop in July 2015, and the Critical Path Innovation Meeting (CPIM) which occurred in November of 2018. Both summaries of these events are on the FPWR website.
  • Other ways to interact with the FDA are through Patient Focused Drug Development meetings (PFDD) or by participating in advisory committees, if they are available. You can become a patient representative or go to an open public hearing where any patient can give their input.

55:26 Q&A session on this PWS research study with Susan Hedstrom; all presenters as panelists

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Topics: Research

Susan Hedstrom


Susan Hedstrom is the Executive Director for the Foundation for Prader-Willi Research. Passionate about finding treatments for PWS, Susan joined FPWR in 2009 shortly after her son, Jayden, was diagnosed with Prader-Willi Syndrome. Rather than accepting PWS as it has been defined, Susan has chosen to work with a team of pro-active and tireless individuals to accelerate PWS research in order to change the future of PWS. Inspired by her first FPWR conference and the team of researchers that were working to find answers for the syndrome, she joined the FPWR team in 2010 and led the development of the One SMALL Step walk program. Under Susan’s leadership, over $15 million has been raised for PWS related research.