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New trial for a ‘molecular band-aid’ to help DMD hearts and lungs

By September 13, 2017September 14th, 2017Homepage News, Research News

Several DMD organizations recently teamed up to fund a Phase 2 clinical trial of a new therapy for Duchenne muscular dystrophy (DMD) – Carmeseal-MD. Carmeseal-MD targets cardiac and respiratory function, the #1 causes of death in boys with DMD. This will be the first trial in boys with DMD. The support for this trial from Charley’s Fund, Team Joseph, Harrison’s Fund, Hope for Gus, JB’s Keys to DMD, Little Hercules, and Michael’s Cause builds on a long history of patient community support for this potential new treatment starting in 2012 with funds from additional organizations including Coalition Duchenne, Ryan’s Quest, and Save our Sons.

We sat down with Dr. John Jefferies, the Principal Investigator for the trial at Cincinnati Children’s Hospital, for a quick Q+A on what’s encouraging about this line of research, what the patient community should know about the trial, and potential next steps.

Q: First of all, let’s talk about something notable here: A lot of times DMD news focuses on exon skipping, gene therapy, gene editing – therapies that target the dystrophin gene itself. Carmeseal-MD doesn’t focus on dystrophin, but it is still critically important to boys and young men with DMD. Why?

Great question. While the replacement of missing or dysfunctional dystrophin with full length and fully functional dystrophin remains the holy grail for the treatment of boys and young men with DMD, I believe that there are nearer-term improvements that can be made in their care. This applies especially to cardiac and respiratory dysfunction, which are the two leading causes of death. Carmeseal-MD is appealing in this regard due to its strong preclinical data and the fact that it can potentially be approved in a shorter time frame than other therapies, so even older boys and young men could still benefit. Lastly, this is a therapy that should apply to all boys with DMD regardless of mutation, an important point in light of the limitations of other late stage therapies.

Q: Tell us more about how Carmeseal-MD works. Why is a drug that ‘seals membranes’ useful in DMD?

It has been known since the mid-1970s that dystrophin is an important membrane protein and that mutations in dystrophin lead to membrane instability and even tears linked to inflow of harmful calcium. Too much calcium in the cell at the wrong time leads to destructive actions in the cell and ultimately cell death (necrosis) followed by fibrosis. Carmeseal-MD has been shown to seal these instabilities and tears, to restore proper calcium balance, and to improve muscle function of damaged hearts and diaphragms.

Q: So what kind of effect do you hope to see if Carmeseal-MD is safe and effective in boys with DMD? What do we know about it from the testing done so far, in both preclinical models and in humans with other conditions?

First of all, Carmeseal-MD has actually already been tested intravenously in more than 2,500 individuals in unrelated diseases with results that give us confidence it will have a strong safety profile when treating boys and young men with Duchenne. And that testing was also done at much higher doses than we’ll be using in Duchenne (where we will also be using a subcutaneous treatment). In fact, two boys outside the United States have actually already been taking the drug through an expanded access program for some time now – one for fifteen months – with no adverse events. So we fully expect Carmeseal-MD to be safe when administered to treat DMD.

Meanwhile, what we have seen through animal testing is that Carmeseal-MD has positive effects on heart and lung function and on skeletal limb muscle. We see these effects in terms of function (e.g., muscle strength) and in terms of reduction of fibrosis. We saw these effects in multiple animal models and a number of laboratories, both corporate and academic. So it is our hope that we will see Carmeseal-MD have positive impact on both heart and lung dysfunction and perhaps also skeletal muscle strength, especially when administered early.

Q: What is the goal for this trial specifically?

With this specific study – the first trial in Duchenne – our goal is to get enough confirmation of Carmeseal-MD’s safety and efficacy in patients to support conducting a larger trial for approval in the US and Europe. At this stage, showing safety is the primary goal – seeing an efficacy signal would be a welcome if not expected addition. This said, it would be fantastic if we see a dramatic biological signal that Carmeseal-MD improves muscle functions in these boys – for example, in respiratory or cardiac function.

Importantly, however, information gained in this trial may also help us confirm that we have the right study design and make tweaks for the next trial. Finally, our hope is this will help raise funds and support for the larger study (which has already been reviewed and approved by the FDA!).

Q: What is the timeline to results that we should have in mind?

We hope that recruitment will start by first quarter 2018. A total of eight non-ambulatory boys and young men will be enrolled. Testing will go on in each boy for 1 year, with quarterly study visits. We hope to announce full results once all boys have completed 12 months of treatment, which will probably be in the second half of 2019. But where we can, with the help of our nonprofit partners, we will share interim updates to keep the community posted.

Q: We also want to set expectations appropriately. This is not a situation where we expect that we’ll go straight from this trial to approval, right? If this study is successful, what needs to happen next to keep it moving toward FDA approval?

Yes, setting expectations is important, especially in this case, since this is the first trial of Carmeseal-MD in DMD. This is a small trial with a very specific purpose. We hope that with this smaller trial we can generate enough data to convince investors and corporate partners to fund a larger trial for approval, maybe with 100+ patients in a prospective, randomized design. That would take us to approval with two trials, already a big success!

Q: If boys want to participate in this study, what should they do? Or if they live outside the U.S. and want to pursue the expanded access program, where do they find information?

For information regarding participation in the study, please contact Cincinnati Children’s Hospital at

Carmeseal-MD is available outside of the United States through Phrixus’s Expanded Access Program and Ethicor Pharma Ltd., a distributor. For more information, please visit or contact!