How an international public/private partnership led to the first therapy for Duchenne muscular dystrophy

By Dr Eric Hoffman, Professor, Department of Pharmaceutical Sciences, Binghamton University, and co-founder of ReveraGen, which developed vamorolone

The Medicines and Healthcare products Regulatory Agency (MHRA) approving vamorolone (Agamree), the first drug for all people with Duchenne muscular dystrophy (DMD), was a momentous occasion. It follows last year’s approval by the European Medicines Agency (EMA) and Food and Drug Administration (FDA) in the US. It makes it the first pharmacological intervention to receive full approval for DMD populations in the UK, US and EU.

The innovative partnership behind its development

Vamorolone was developed utilising an innovative public and private participation model with central governments, non-profit foundations and commercial stage research and development organisations working in co-ordination to advance the development programme from discovery through clinical trials all the way to drug approval.

Patient-focused foundations including the Muscular Dystrophy Association (US), Parent Project Muscular Dystrophy foundation (US), Joining Jack (UK), Duchenne Research Fund (UK), and Duchenne UK (UK), under venture philanthropy models (shared risk, shared benefit) provided financial support for specific development activities. Further investments in the form of licensing and milestone payments by Actelion, Idorsia, and Santhera provided key additional resources to complete the vamorolone development programme.

The US Department of Defense through the Congressionally Directed Medical Research Programs (CDMRP) funded research for early drug discovery, clinical outcomes research, and natural history studies by the Co-operative International Neuromuscular Research Group.

The National Institutes of Health helped de-risk the non-clinical programme by completing robust confirmatory efficacy studies and implementing an improved synthetic process for drug manufacturing (National Center for Advancing Translational Sciences – TRND programme) and supported clinical trials (National Institute of Neurological Disorders and Stroke – SBIR programme). The European Commission provided a Horizons 2020 grant for the clinical trial programme through Newcastle University in the UK.

Leveraging infrastructure

The overall vamorolone programme leveraged infrastructure for drug development and clinical trials in DMD, with extensive peer review and feedback at each step of the development pipeline. A broad swath of the international stakeholders and the academic research community has been intimately involved with bringing vamorolone to approval.

“The vamorolone development program underwent extensive de-risking, through peer review by both governmental and non-profit foundation advisory boards,” said Dr. Michela Guglieri, Professor of neuromuscular disorders and Consultant Neurologist at Newcastle University, and principal investigator on the EC Horizons 2020 award, “this, coupled with extensive stake-holder involvement in design and implementation of the clinical trials likely led to the robust efficacy and safety data observed”.

Vamorolone received Priority Innovative Medicine designation from the MHRA in 2019, and five UK academic medicine sites had critical involvement in the vamorolone clinical trials (Newcastle [Dr. Volker Straub], Glasgow [Dr. Iain Horrocks], Leeds [Dr. Anne-Marie Childs], London [Dr. Giovanni Baranello], Liverpool [Dr. Stefan Spinty]).

“The Cooperative International Neuromuscular Research Group (CINRG) and the Therapeutic Research in Neuromuscular Disorders Solutions (TRiNDS) coordinating center brought extensive disease-specific expertise to the clinical trial programme,” said Dr. Paula Clemens, Professor of Neurology at the University of Pittsburgh, and Study Chair of the Phase 2a and Phase 2b clinical trials.

“Without the extensive outcomes research and collaborative structure of the CINRG group, obtaining the robust data from the vamorolone trials would likely not have been possible,” Dr. Clemens noted.

A key aspect of de-risking of the vamorolone programme was de-risking in the early pre-clinical space. “One reason for the program’s success is robust foundational preclinical in vitro, and in vivo data using well-standardized outcome measures that our laboratories have developed over the last two decades in collaboration with the international TREAT-NMD network,” said Dr. Kanneboyina Nagaraju co-founder of ReveraGen, and Dean of the School of Pharmacy and Pharmaceutical Sciences, Binghamton University – State University of New York.

“The Foundation to Eradicate Duchenne has been a participant in the vamorolone project since the beginning, and I am delighted to see vamorolone be approved,” said Joel Wood, President, and Chief Executive of the foundation.

“Children’s National Hospital was the initial home for early vamorolone research, and ReveraGen the first spin-off company,” said Mark Batshaw, M.D., distinguished investigator in the Center for Genetic Medicine Research at Children’s National, “the approval underscores the importance of supporting clinicians and researchers who are developing solutions to advance healthcare for children.”

Supporting Duchenne non-profits  

We are delighted that proceeds from the future sales of vamorolone will be shared with over a dozen non-profit foundations, continuing the shared risk – shared benefit agreements between ReveraGen and these foundations.

Significant portions of the proceeds from sales-based milestone payments and dividends that are anticipated to be coming to ReveraGen as a result of licensing the product will be distributed to non-profits based on sales of vamorolone.

Published on 16 January 2024

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