As recognition of fatty liver disease and non-alcoholic steatohepatitis (NASH) as a true global health crisis rises the need to collect, curate, and share relevant information in a timely fashion grows as well. The GLI NASH News is intended to meet that need and facilitate collaboration across the emerging NASH Community on a monthly basis.
We appreciate your feedback and content contributions. Please contact nash@globalliver.org
GLOBAL LIVER INSTITUTE
GLI Perspective
GLI CEO Donna R. Cryer, JD participated as faculty in the 4th Paris NASH Summit July 5-6, 2018, presenting on the Science & Art of Patient-Engaged Clinical Trial Design. Mrs. Cryer deconstructed the meaning of “patient-engaged”, the characteristics of patient-engaged trials, and provided a framework for more expansive thinking about how to partner with patients and patient advocates in research rather than interact and view them as subjects or even participants. Evolving patient roles across clinical research include:
- De-risking the market – improving the climate for investment in liver therapies
- Focusing the portfolio – matching patient-defined needs with scientific opportunities and regulatory endpoints
- Refining the protocol – providing insights to assess patient burden and barriers to participation
- Targeting recruitment – leveraging social media and peer mentoring to support enrollment and retention
- Aligning with regulators – collaborating on patient reported outcomes measures and patient-focused drug development meetings
- Collecting Real World Evidence – defining, generating, and share data to inform post-approval assessments of the value of therapies beyond the clinical trial setting
GLI and 1st International NASH Day
The Global Liver Institute participated as lead advocacy organization partner in the inaugural International NASH Awareness Day including a WebTV interview with Dr. Arun Sanyal on the future of NASH. http://youtu.be/vDt5kHXgWEk
GLI Advocacy Facebook Group
GLI recently launched its Liver Health Advocates Facebook group! This platform is being used as an online space for you and your peers to discuss your advocacy needs, share your experiences, and connect with each other. We encourage you to invite your fellow liver patients, support networks, and others who help advocate for liver health!
NASH Council
Want to be a member?
Members have the benefit of accessing the secure NASH Council portal with Workgroup meeting minutes, other members’ contact information, and will have the opportunity to participate in our all member council meeting in June.
Physicians Committee For Responsible Medicine
The Physicians Committee is comprised of over 12,000 physicians who work to change the way physicians treat chronic diseases. Through prevention, this organization empowers patients to take control of their own health and healthcare.
Recently, this organization launched the Nutrition Study for Weight Loss and Metabolism that seeks to find the effects of an intervention diet on postprandial metabolism, i.e., after lunch or dinner. This randomized, controlled trial aims to determine whether weight reduction resulting from a plant-based dietary intervention is caused, in part, by altered postprandial metabolism. Using a low-fat, plant-based diet for 16 weeks, the study will measure changes in postprandial metabolism and insulin sensitivity.
Recruitment is now open until August. For more detailed information about this study or to become a participant visit PhysiciansCommittee.org/study.
The Liver Forum
The Liver Forum, a member of the NASH Council and leading convener in the NASH clinical development/regulatory space, reports numerous NASH activities in June and early July. GLI was excited to cross paths with Liver Forum executives in numerous NASH policy and planning events around the world including at the GLI NASH Council annual meeting where Liver Forum Project Manager Katherine Greene participated in a panel discussion, and at a Congressional briefing conducted with GLI and with NASH thought leaders as part of International NASH Day.
University of Michigan NAFLD Program
The University of Michigan NAFLD Clinic continued to promote NAFLD/NASH awareness with a focus on optimization of diet and exercise during the recent Digestive Disease Week (DDW). As part of this conference, Michigan NAFLD Clinic leadership held two sessions on the role of diet and exercise in the treatment of NAFLD and NASH. During these presentations, speakers reviewed the evidence in support of healthy eating and increased physical activity as the first line treatment. From a diet perspective, the benefits of a carbohydrate controlled or Mediterranean-based diet were highlighted in addition to minimization of high fructose corn syrup and red or processed meats. Regarding physical activity, targeted exercise goals of at least 150 minutes per week of moderate or 75 minutes of vigorous intensity exercise were outlined in addition to minimizing overall sedentary activity such as sitting time. Presentations concluded with summary points on methods to help implement these lifestyle interventions in real world clinical practice including assessing gaps in patient knowledge, objectively evaluating and tracking diet and exercise, and using pre-existing tools and interventions such as referral to nutritionists and programs targeted towards patients with diabetes and metabolic syndrome.
University of Michigan (UM) NAFLD Clinic recently launched a Multidisciplinary Obesity Clinical and Research Conference in conjunction with endocrinology, cardiology, nutrition, bariatric surgery and bariatric endoscopy. This quarterly conference provides a forum for presentation of complex obesity-related patient care cases in addition to discussion of ongoing obesity-related research topics. In this setting, clinicians are able to obtain real-time input from experts across multiple specialties to facilitate patient care. From a research perspective, investigators can solicit feedback about obesity-related research proposals. This collaborative also facilitates cross-disciplinary scientific inquiries.
Industry
Madrigal Pharmaceuticals
On May 31, 2018, Madrigal Pharmaceuticals announced that its phase 2b clinical trial testing MGL-3196 was statistically significant in reducing liver fat and improving NASH conditions in patients after 36 weeks. At week 12, some patients had already experienced a statistically significant reduction of liver fat, equal to or more than 30%, as well as “39% NASH resolution.” This oral drug is taken once-daily and is a liver-directed thyroid hormone receptor, β-selective agonist Trial. The “thyroid hormone, through activation of its beta receptor, plays a central role in controlling lipid metabolism”; thus drugs like MGL-3196 can effectively respond to excess fat proliferation in the liver.
Galectin Therapeutics Phase 3 of GR-MD-02 Clinical Trials
Galectin Therapeutics Inc. is proceeding with Phase 3 of their GR-MD-02 clinical trial program, with guidance from the US Food and Drug Administration. Researchers aim to further investigate the effects of the galectin-3 inhibitor GR-MD-02 in NASH cirrhosis. GR-MD-02 is a complex carbohydrate that targets galectin-3, a critical protein in the progression of fatty liver disease and liver fibrosis. Phase 3 of the program follows encouraging results from Phase 2b of their NASH-CX trial. Data from Phase 2b yielded statistically significant effects for treatment of hepatocyte ballooning and reducing development of new esophageal varices. Researchers will be examining changes in hepatic venous pressure gradient (HVPG) or progression of esophageal varices (enlarged veins) during Phase 3 of the study. Details regarding timing and costs will be announced later this month.
Find out more details about this study here.
Regulatory
Food and Drug Administration (FDA)
On June 12, FDA commissioner Scott Gottlieb, M.D. announced plans for the FDA to amplify the patient voice in the drug development process. The FDA would like to skillfully blend “patient experience data and other relevant information from patients and caregivers” with FDA professionals and scientists. Gottlieb believes that as the nature of drug development becomes more targeted, the process requires a more patient-focused approach as well. Patient insight is a necessary step in both “medical product development and regulatory decision-making.” A guidance document on Patient-Focused Drug Development (PFDD) is open for review and revisions from the public.
Department of Health and Human Services (HHS)
On June 4, 2018, HHS Deputy Secretary Eric Hargan commented on “Time to Deliver,” a report from the World Health Organization Independent High-level Commission on Noncommunicable Diseases (NCD). Hargan discussed the critical need for improvement in the NCD burden on a global scale. Global public health activity demands a mutually-beneficial relationship between the public and private sectors. Commenting on the value of education in NCD prevention, Hargan said both public health and education sectors can effectively impact the information disseminated to young people worldwide
NASH is an example of a NCD that can be prevented and/or resolved by lifestyle modifications, suggesting that national and local governments as well as private enterprises should promote healthy choices among their constituents and employees. Healthy lifestyles are a key component of combating several NCD’s worldwide. Proper management of NASH may potentially be attributed to productive coalitions among public institutions and private sector organizations. For instance, in the U.S., partnerships between private fitness organizations and federally-subsidized insurance plans may diminish the effects of NASH among populations.
Clinical Trials
Research & Studies
Charité – Universitätsmedizin Berlin Radiological Technology Testing
A team of researchers and physicians from Charité – Universitätsmedizin Berlin announced their success in testing a new radiological technology used to assess overweight adolescents with NASH. This technology, referred to as ‘time harmonic elastography’ (THE), is a noninvasive, ultrasound-based measurement in evaluating liver fibrosis. The study consisted of 67 overweight adolescents diagnosed with NAFLD. These patients were positioned on a trolley, which produces vibration waves capable of penetrating tissue depths of obese patients. The waves were then measured, providing information on the liver stiffness per individual. The team’s findings exhibited accuracy in distinguishing between levels of fibrosis severity (mild, moderate and advanced fibrosis). More testing needs to be done using THE, but should future studies produce similar results, researchers are optimistic that this technology could help reduce the need for invasive liver biopsies, and assist in long term monitoring of patients and their treatment outcomes.
Official results of the study can be found here.
For Your Calendar
Aug 15-17: NASHP’s 2018 National Health Policy Conference, Jacksonville, Florida.
Sept 21-22: GLI’s Advanced Advocacy Academy
Oct 22-24: 2nd NASH Summit. Frankfurt, Germany
Nov 9-13: The Liver Meeting 2018. San Francisco, CA
Further Reading
Intercept’s Obeticholic Acid Therapy and NASH
Galectin-3 inhibitor improves hepatic ballooning in NASH