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Medical Network

Fall, 2020

New Drugs for Juvenile Myositis Symposium

Dr. Heaton

Summary by Cure JM’s Chief Scientific Officer, Andrew Heaton, PhD.

The Cure JM Foundation and the Cure JM Center of Excellence at Duke University co-hosted a virtual symposium, New Drugs for Juvenile Myositis, on October 17, 2020. The core mission of the foundation is to foster research that leads to better treatments and ultimately a cure for Juvenile Myositis (JM). As JM is a rare pediatric auto-immune disease it suffers from a paucity of drugs that have a specific label claim. To date, the treatment of JM has relied on the use of off-label drugs as part of consensus treatment protocols. The consensus treatment protocols are based on years of different treatments and concomitant research by the global pediatric rheumatology community. The diligent research into JM has helped uncover genetic markers that are linked to a JM predisposition and the definition and delineation of different disease phenotypes. The complexity of the drivers of JM has hindered the development of validated in vitro and in vivo models of the disease. The drugs used to treat JM are therefore largely based on the migration of drugs prescribed for other indications. As the JM research community uncovers more data on the underlying pathogenesis and etiology of the disease, the process of migrating drugs is being significantly improved.

The symposium’s focus was on drugs that are either in clinical studies for JM, or there are increasingly compelling data sets to suggest their utility in treating JM. The symposium was structured to define: different druggable targets in JM, up to date examples of drugs in JM clinical trials, and drugs that may enter JM clinical trials within the next few years.

The initial focus of the symposium was a broad discussion on JM presented by Jeffrey Dvergsten, MD, of Duke University’s Children’s Health Center. Dr. Dvegsten’s elegant and detailed presentation set the scene for the symposium, detailing the current understanding of JM pathogenesis, the role of the innate and adaptive immune systems in pathogeneses, the rationale for the current consensus treatments and finally, the exciting future of new potential drug targets and the underlying science behind these new targets.

One of the key drivers of JM is the interferon signal transduction. While Dr. Dvergsten’s presentation covered this aspect of the disease and its potential as a drug target for JM, the importance of the interferon signal mechanism was highlighted in a more detailed presentation by John O’Shea, MD, of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) at the National Institutes of Health (NIH). Dr. O’Shea, gave an elegant and detailed description of this highly complex signal transduction mechanism, detailing the number of different points on the pathway that are currently being targeted or are potential targets for future discovery programs.

Following Dr. O’Shea, Hanna Kim, MD, MS, of NIAMS at the NIH, presented data on the JAK inhibitor, baractitinib, a class of drug that targets the interferon pathway. While Dr. Kim’s study was only on four patients, the data presented demonstrated considerable promise for JAK drugs in JM. Dr. Kim presented data on the four patients that had an early and sustained decrease in physician and patient global activity score and a notable improvement in strength and skin activity. Significantly, Dr. Kim reported that patients were able to decrease other immunosuppressive medications. The JM community is eagerly anticipating the next larger trial of baracitinb in JM patients.

Another target within the interferon pathway is the SOCS1. This suppressor of cytokine signaling data was presented by Charlly Kao, PhD, of the Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP). Dr. Kao presented some encouraging early-stage data on kinase inhibitory region peptide mimetic. The initial work on this peptide mimetic came out of the University of Florida. Dr. Kao presented their detailed background data comprising significant resolution of skin lesions in an in vivo lupus-prone mouse model. Dr. Kao also presented further compelling data in a novel imiquinoid induced murine psoriasis model, as well as equine uveitis model. CHOP plans to take this exciting drug from animal models into the clinic.

The symposium shifted focus from interferon pathway targets to drug treatments. The first presentation was from Rodolfo Curiel, MD, FACP, FACR, of Medical Faculty Associates at The George Washington University. Dr. Curiel is studying the human fusion protein abatacept in Juvenile Dermatomyositis (JDM) patients. Dr. Curiel detailed the mechanism of action of abatacept, and the compelling data that has already been acquired on this drug in Adult Dermatomyositis (DM). The data in Adult DM included significant improvement in core set measures at three and six months, patient global activity, and extramuscular global activity. Dr. Curiel detailed the inclusion and exclusion criteria for the JDM clinical trial, highlighting that the trial requires only one more patient to enroll to finalize the study and allow for a full data analysis in JDM.

Calcinosis is often associated with JDM and has been associated with worse physical function. Adam Schiffenbauer, MD, of the National Institute of Environmental Health Sciences at the NIH, presented data on a trial of sodium thiosulfate in JDM patients with calcinosis. Dr. Schiffenbauer detailed the issues around assessing and quantifying calcinosis, a requirement to quantify the effect of a drug targeting calcinosis. Further discussion compared and contrasted a number of drugs that have been used to treat calcinosis in JDM patients, setting the scene for the comparative advantage of the sodium thiosulfate trial. Dr. Schiffenbauer detailed the multiple mechanisms by which sodium thiosulfate could work and detailed the inclusion and exclusion criteria for the trial. Like the abatacept trial, the current trial has not completed enrollment, which is required to lock the data sets and complete the analyses to determine the efficacy of sodium thiosulfate in JDM patients with calcinosis.

Corticosteroids are a class of drug that underpin many of the consensus treatment protocols for JDM. Eric Hoffman, PhD, Vice President of Research, ReveraGen, gave a finely detailed history on the steroid replacement he has been taking through clinical trials. The drug ReveraGen is developing, vamorolone, is a potential significant replacement for the standard of care steroids used to treat JDM. Dr. Hoffman detailed that standard of care steroids have two mechanisms of action: transactivation and transrepression. The former leads to an array of unwanted side effects and the latter to the efficacy of steroids. Vamorolone has been demonstrated to have significantly less transactivation while retaining similar levels of transrepression, which is ideal for a steroid replacement. Dr. Hoffman detailed the in vitro and in vivo work that supported the switching of the transactivation. Vamorolone is currently in a licensure trial for Duchenne’s Muscular Dystrophy and is expected to get approval later in 2021. The ReveraGen, Duke and Cure JM team are now looking at how to start a clinical trial of this exciting drug in a JDM cohort of patients.

The final presentation for the day was on a novel drug, lenabasum, which targets the endocannabinoid system. Quin Dinh, MD, Vice President, Head of Medical Affairs, Corbus Pharmaceuticals, gave an elegant, detailed discussion on the cannabinoid system, including validation of activating the CB2 receptor, that is expressed in activated immune cells. The discussion detailed the extensive use of well-engineered models including CB1 and CB2 knock-out mouse models. These models validated that CB2 modulates inflammation and fibrosis. Dr. Dinh detailed the exciting results to date in several studies in adults of lenabasum, including its significant reduction of skin disease in patients that were refractory to other immunosuppressive agents.

The symposium wrapped up with a thought-provoking talk by Kaveh Ardalan, MD, of Duke University’s Duke Children’s Health Center. Dr. Ardalan discussed looking beyond traditional biomarkers of success in a clinical trial. He emphasized treating the whole patient and underlined that the mental health of patients and their families are very valid determinants of the success of a clinical trial.

You can watch the full symposium:

For more information on the trials currently enrolling patients, click here.
If you have further questions, please email .


Nutrition and Exercise

Each month, Cure JM hosts a virtual Town Hall on important healthcare topics. This Town Hall covers common questions caregivers have about nutrition and exercise. It was presented by Brian Feldman, MD, MSc, FRCPC and Julie Shevlin, MS, RDN.

Dr. Feldman is a Professor of Pediatrics, Medicine, Health Policy Management & Evaluation, Dalla Lana School of Public Health at the University of Toronto. Julie Shevlin, MS, RDN, is a pediatric registered dietician nutritionist and a mother to a daughter diagnosed with JDM in 2009.

This issue is brought to you with the support of:

Bristol Myers Squibb logo
CSI Pharmacy Clinical Specialty Infusions, LLC
Pharmaceutical Companies of Johnson & Johnson

Cure JM welcomes your input, questions and experiences. Please email to share your input.