How the VISION of DMD patients helped the development of a new steroid
Approval of AGAMREE®
The approval of AGAMREE®, (formerly known as vamorolone) on Monday 18 December by the European Medicines Agency for the treatment of Duchenne Muscular Dystrophy (DMD) represents a landmark event for the rare disease community. AGAMREE® is a novel designer steroid-like drug. The development has been driven by an academic and patient led venture philanthropy approach unlike the usual pharma development.
Patient funding was instrumental in passing this drug through the ‘valley of death’, early development and innovation phases. This exciting venture philanthropy model accelerated the development with access to funding, but importantly also the expertise, knowledge and energy of patient organisations.
Their involvement sheds light on what lessons can be learned, how clinical trials can be better designed and how data can be returned to patients, in addition to promoting access to patients and replicated to assist the development of future drugs or treatments for rare diseases. These activities supported the highly innovative team at ReveraGen Biopharma who drove the development work.
DMD is an early-onset incurable and ultimately fatal rare muscle wasting disease, predominantly affecting males. As this disease progresses, these boys will lose their ability to walk, self-feed, and breathe independently. DMD also leads to further serious medical problems, particularly relating to cardiac and respiratory failure which is currently the primary cause of death in Duchenne patients.
In Europe so far only one drug for Duchenne received conditional approval, but corticosteroids are widely recognized and used to increase muscle strength, delay disease progression and are part of the International Standards of Care. However, long-term use comes with severe side effects which can limit their use over time. These include deleterious effects on bone health and growth.
Duchenne Patient organisations
Patient foundations for DMD are world leaders. They are well established, highly organised and champion numerous research funding initiatives. These foundations provide advocacy, support and knowledge exchange that is invaluable to both patients and their family members impacted by this distressing disease.
It is their foresight and willingness to push frontiers and take financial risks that enabled the initial preclinical and early clinical phases of the development of AGAMREE to progress.
Patient foundation, by providing the funding was critical to ‘de-risk’ the early but essential activities. Patient groups identified that a steroid with fewer side effects was a huge benefit to the lives of their boys. It is their foresight and willingness to push frontiers and take financial risks that enabled the initial preclinical and early clinical phases of the development of AGAMREE® to progress. Significantly, in trials, treatment with AGAMREE® showed no restrictions of growth and no negative effects on bone metabolism.
World Duchenne Organization partner in Vision-DMD project
The venture philanthropy continued with the successful application to the EC Horizon 2020 Programme, New therapies for rare diseases, with the VISION-DMD project accessing €6 million euros towards the Phase 2 clinical studies. This funding leveraged further NIH grant funding and continued investment from patient groups. The funded studies were successfully conducted in Europe, Israel, the US and Australia, and continued patient group participation as World Duchenne Organization, a partner in the project, played a vital role in supporting the project activities and clinical trials.
Santhera are now taking AGAMREE forward and plan to make the drug available as soon as possible, with a first commercial launch planned early next year 2024 in Germany.
Supporting information
The VISION-DMD project advanced and accelerated the clinical development of the orphan drug vamorolone (also known as VBP15) for the treatment of Duchenne Muscular Dystrophy (DMD) through a series of Phase 2 clinical trials being conducted in Europe, the US, Canada, Israel and Australia, leading to drug registration. Availability of vamorolone may deliver a significant advance in the standard of care for all patients with DMD regardless of mutation.
AGAMREE® (Vamorolone) is an innovative first-generation dissociative steroid-like drug specifically designed to retain or improve the benefits of CS treatment in DMD whilst aiming to reduce side effects that currently restrict their use.
This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement number 667078. Patient Organisation funding is summarised here: Patient Group Funders (vision-dmd.info). the project was also supported by NIH funding.
About Duchenne Muscular Dystrophy (DMD)
DMD is a progressive and severe, rare genetic disease affecting approximately 1 in 3,500 to 5,000 male births. The natural history of the disease is devastating. The boys become progressively weaker during childhood. If they are not treated with steroids they losing independent ambulation around 10 years and death occurs by early adulthood often due to cardio-respiratory failure. The disease remains incurable, though long-term use of corticosteroids (CS), has increased life expectancy. Long-term use of steroids is part of the International Standards of Care, however these Standards are not everywhere implemented. In February 2017, Emflaza (Deflazacort) became the first steroid treatment for DMD to be approved by the Food and Drug Administration (FDA) in the US. In other countries CS are used off label. Concerns about the severe side effects of all CS may greatly restrict their prescription.
Venture Philantrophy Vision-DMD is a patient group and academic researcher driven project, with funding for drug development being focused on innovative venture philanthropy through patient group funding and public investment. The project wanted to be a model for affordable rare disease drug development.
The project also provided key research on innovative exploratory biomarkers and undertook novel MRI techniques to assess feasibility and clinical relevance.
The project consortium brought together leading international teams in the DMD field including Newcastle University’s John Walton Muscular Dystrophy Research Centre in the UK, the Cooperative International Neuromuscular Research Group (CINRG) based in the US and the European Research Infrastructure Consortia (ECRIN) based in France. The involvement of World Duchenne Organization (formerly UPPMD) based in The Netherlands, ensured DMD patient groups had input into the project. Reveragen Biopharma (UK/US), Ceratium Ltd (UK) and University Hospital Motol (Czech) completed the project consortium.
For more information: [email protected]
Press release Santhera: https://www.santhera.com/assets/files/press-releases/2023-12-18_EC-approval_e_finalx.pdf
