The Story of the Foundation to Eradicate Duchenne


Media Release
October 17th, 2019

Vamorolone Designated Promising Innovative Medicine (PIM) for treatment in Duchenne muscular dystrophy

Rockville, MD

In the UK the Early Access to Medicines Scheme (EAMS) is a regulatory path by the MRHA that aims to give patients with life threatening or seriously debilitating conditions access to medicines that do not yet have a marketing authorization when there is a clear unmet medical need.  The initial step in this process is Promising Innovative Medicine (PIM) designation.

 

Co-founders of Duchenne UK Alex Johnson and Emily Crossley said, “We are delighted that MHRA has given PIM status to Vamorolone as a treatment for Duchenne Muscular Dystrophy. A PIM designation is the first step of a process that could allow patients earlier access to a new medicine. This is part of the Early Access to Medicines Scheme which Duchenne UK and Joining Jack lobbied for in 2014. We are pleased to see that the scheme may be used for Vamorolone.”

 

UK foundations that have aided the development of vamorolone for DMD include Joining Jack, Duchenne Children’s Trust, ActionDuchenne, Alex’s Wish Foundation, and Duchenne Research Fund.

 

Vamorolone is a first-in-class drug that targets multiple biochemical pathways in DMD patient muscle simultaneously, and in initial open label studies has shown improvements of patient muscle function.  A pivotal trial that may lead to drug approval is currently enrolling patients age 4 to 7 years at 6 sites in the United Kingdom (Newcastle University, Royal Hospital for Children [Glasgow], Alder Hey Children’s Hospital [Liverpool], Leeds Teaching Hospital Trust, Great Ormond Street Institute of Child Health [London] and University Hospitals Birmingham). Information on the currently recruiting vamorolone clinical trial with contact information for UK recruitment sites can be found at clinicaltrials.gov.

 

About the UK Early Access to Medicines Scheme (EAMS)

The UK’s industry-sponsored EAMS aims to give patients with life threatening or seriously debilitating conditions access to medicines that do not yet have a marketing authorization when there is a clear unmet medical need. The EAMS is a two-step process:

Step I is the Designation as a Promising Innovation Medicine (PIM). The PIM designation is an early indication that a medicinal product is a promising candidate for EAMS and gives reassurance that its clinical development is on track by having an early review of its data by the medicines regulator.

Step II is the Scientific Opinion by the Medicines and Healthcare products Regulatory Agency (MHRA, UK regulatory agency). The Scientific Opinion describes the benefits and risks of the medicine and supports the prescriber and patient to make a decision on using the medicine before its license is approved.


Media Release
October 5th, 2019

Top-line data of 18-month vamorolone treatment of Duchenne muscular dystrophy patients shows continued improvement of symptoms with reduction in corticosteroid safety concerns

Rockville, MD  –

A late-breaking presentation at the 24th International Annual Congress of the World Muscle Society (WMS) in Copenhagen, Denmark reported top-line data from 18-month treatment of Duchenne muscular dystrophy (DMD) patients (VBP15-LTE trial).  The data was presented by Dr. Eric Hoffman, CEO of ReveraGen.

Vamorolone is a first-in-class steroidal anti-inflammatory in development as treatment for DMD to substitute for corticosteroids (prednisone, deflazacort) that are currently recommended.  48 DMD patients treated for 6 months over a broad dose range (0.25 to 6.0 mg/kg/day) showed dose-related improvements in multiple gross motor outcomes (Hoffman et al. 2019).  Upon exiting the 6-month trial, nearly all patients and their physicians chose to continue vamorolone treatment.  45 boys enrolled in a 2-year long-term extension study (VBP15-LTE; NCT03038399), and all dose escalated to 2.0 or 6.0 mg/kg/day of vamorolone.

At the WMS presentation, Dr. Hoffman reported motor function data from 23 patients treated with 2.0 or 6.0 mg/kg/day vamorolone for at least 18 months compared to matching steroid-naïve patients from the Duchenne Natural History Study (DNHS) conducted by the Cooperative International Neuromuscular Research Group (CINRG) (McDonald et al. 2018).  Vamorolone treatment significantly improved the velocity of 10-meter run/walk (p=0.005), and 4-stair climb (p=0.036) relative to historical controls.  Time to stand from supine showed significant improvements within the vamorolone-treated patients from baseline to 18-months (log seconds p=0.007; velocity p=0.017), but comparison to CINRG DNHS steroid-naïve patients did not reach significance (p=0.08).  In addition, motor function outcomes of vamorolone-treated DMD boys were compared to age-matched prednisone-treated CINRG clinical trial patients (Escolar et al. 2011). Both groups (vamorolone and prednisone) showed similar improvements in these gross motor outcomes.

Vamorolone-treated DMD boys showed normal growth rates, and less physician-reported weight gain and Cushingoid features compared to published studies of prednisone and deflazacort (Griggs et al. 2016).  The molecular and clinical data suggest that vamorolone is a dissociative steroidal drug that maintains efficacy and has a lower level of the adverse effects that are seen with the currently recommended corticosteroids for the treatment of DMD.

“Our findings suggest that vamorolone results in improvement in DMD patient function, similar to that of corticosteroids, but with less side effects, including no stunting of the growth of DMD children”, said Dr. Hoffman.  DMD patients show poor compliance with corticosteroid treatment, even though it is standard of care, and this is primarily due to intolerable side effects (Cowen et al. 2019).  “The poor growth of DMD boys after taking corticosteroids is of concern to patients and families, and the lack of this growth failure with vamorolone treatment is an objective outcome of improved safety”, said Dr. Paula Clemens, Study Chair, Professor of Neurology at the University of Pittsburgh.

The vamorolone studies were carried out by the Cooperative International Neuromuscular Research Group (CINRG), an international collaborative of expert pediatric neuromuscular research centers, with studies coordinated by TRiNDS LLC and ReveraGen BioPharma.

 

Media contacts:

Eric Hoffman.  Email: eric.hoffman@reveragen.com

 

NOTES:

About Duchenne muscular dystrophy

Duchenne muscular dystrophy is a rare genetic disease that predominantly affects young boys.  Loss of the large protein, dystrophin, in muscle leads to persistent damage to muscle.  DMD is a progressive disease, with gradual loss of muscle and weakness over 20 years leading to loss of walking abilities, and shortened lifespan.

About ReveraGen BioPharma

ReveraGen was founded in 2008 to develop first-in-class dissociative steroidal drugs for Duchenne muscular dystrophy and other chronic inflammatory disorders.  The development of ReveraGen’s lead compound, vamorolone, has been supported through partnerships with foundations worldwide, including Muscular Dystrophy Association USA, Parent Project Muscular Dystrophy, Foundation to Eradicate Duchenne, Save Our Sons, JoiningJack, Action Duchenne, CureDuchenne, Ryan’s Quest, Alex’s Wish, DuchenneUK, Pietro’s Fight, Michael’s Cause, and Duchenne Research Fund.  ReveraGen has also received generous support from the US Department of Defense CDMRP, National Institutes of Health (NCATS, NINDS, NIAMS), and European Commission (Horizons 2020).  www.reveragen.com

About vamorolone

Vamorolone (previously VBP15) binds to the same cellular receptors as traditional glucocorticoid drugs, but unlike these, does not enable dimerization of the drug/receptor complexes.  This leads to a separation (dissociation) of anti-inflammatory benefit from safety concerns.  In published Phase I studies in healthy adult volunteers, vamorolone showed reduction or loss of most side effects of glucocorticoids, as measured by blood biomarkers over a 2-week treatment period.  Vamorolone has been granted Orphan Drug status by both FDA and EMA, and received Fast Track designation by the FDA.

About the Cooperative International Neuromuscular Research Group (CINRG)

CINRG was founded in 2000 as an international academic clinical trial network, with a focus on pediatric neuromuscular disease.  CINRG has enrolled over 1,500 patients into clinical research studies.  Recent studies include the CINRG Duchenne Natural History Study (DNHS) with 440 DMD patients and over 100 healthy peers followed by expert neuromuscular physicians in 20 sites in 10 countries.  See www.cinrgresearch.org www.trinds.com


 

What is Duchenne Muscular Dystrophy?

What is Duchenne Muscular Dystrophy?

Duchenne Muscular Dystrophy is a relentless, cruel disease.  It is the world’s #1 lethal childhood genetic disorder.  The Foundation to Eradicate Duchenne (FED) exists to fund scientific research for treatments for today’s generation of boys and young men who suffer from Duchenne.

FED is a small group of families with sons who have Duchenne.  We are focused on leveraging the dollars we raise to the most aggressive research that is within reach of our sons.  This is an important distinction from other organizations in the neuromuscular community, with whom we do our best to work cohesively.  We are supporting clinical trials on drugs that have already crossed the threshold from theoretical and speculative.

Founded in 2001, the FED has raised many millions of dollars, and much progress has been made.  Duchenne was once a hopeless disorder that had a predictable trajectory – one that typically took away lives in teenage years or the early twenties. Today, it is difficult to establish an expected life expectancy based on strides that have been made.  But there are desperate needs to push Duchenne-specific therapies out of the scientific pipeline and into the marketplace.  We are, in three words: not there yet.

Amazing progress has been made, but we feel anguish for the dreams that are unfulfilled, for the lives that are cut far too short.  Our sons suffer in silence.