Portrait of Duchenne – Ataluren a promising treatment for DMD

Ellen Welch, PhD

Group leader biology at PTC Therapeutics, South Plainfield, New Jersey, USA


In this fourth interview of our series “Portrait of Duchenne”, La Force DMD talks with Ellen Welch, Ph.D., Group leader biology at PTC Therapeutics. She has been working on a treatment for DMD called ataluren (Translarna™). She earned her Ph.D. at the University of Massachusetts Medical School, where she worked on nonsense mutations and how they affect gene expression. 


Already approved and reimbursed in Europe

Ataluren is a treatment for Duchenne muscular dystrophy (DMD) that has been approved for use in Europe and even reimbursed in the UK. It is currently under the FDA review for marketing approval in the USA. Unfortunately, PTC Therapeutics has not filed an application to market ataluren in Canada. We met the PTC Therapeutics team to gather information to understand how exactly this treatment works. New clinical trials are opening for children with DMD. We hope this treatment will be available soon for the Canadian DMD community.


A treatment for nonsense mutation

Ataluren is the first treatment to address an underlying cause of DMD: a nonsense mutation. The nonsense mutation occurs about 13% of the DMD population. As you probably know, DMD is a rare, progressive genetic disorder. Children born with DMD do not produce enough dystrophin, an important structural component of muscle, causing muscle cells to break down and die. Some cases of DMD are caused by nonsense mutations, which are errors in the genetic code that prematurely stop the production of dystrophin.

Our goal, with this interview, is to help you understand key information about the nonsense mutation and how the treatment works.


In the video, Dr. Ellen Welch answers our questions about nonsense mutation and ataluren


What is a nonsense mutation?

So I think what you first have to understand is that all the genetic information in the cells is encoded in DNA. You make a copy of DNA into RNA (ribonucleic acid) and then RNA is the template that the cell uses in order to make a protein. So when you have a nonsense mutation in a gene – so if you took the DMD gene, for instance, and you get a point mutation in DMD – when that DNA is copied into RNA, that point mutation can now be part of the RNA that becomes what’s called a premature stop codon. So this is what Anakin has: he has a premature stop. So what does that mean? It means when the cell uses this piece of RNA to make a protein, that it cannot make a full-length protein because it has this premature stop signal. It’s got a signal in the cell that says stop making the protein. And that signal is in the wrong place.


How does ataluren help the production of dystrophin?

And what dystrophin does is it links the membrane of the muscle to the inside of the cell – acts as like a shock absorber – so when you walk, your muscle cells don’t break open. So when you only have one part of dystrophin, it can’t make that link. So if you can read through the premature stop, now you can trick, what ataluren does, it tricks the cell and says don’t stop there, keep going. And then you can make the full-length protein, so now you can link the inside and the outside of the cell together, and that helps to stabilize the muscle. So what we know from what ataluren does is, when you translate – encounter the premature stop codon – the cell machinery is able to insert another amino acid, one of the building blocks for a protein, there. So when it inserts that building block, then it can go on and make the rest of the protein normally. You just have to get through that one hurdle, but that hurdle is a component of the cellular machinery that’s very highly regulated. Because it’s important for the cell, when it really comes to the normal stop signal, to stop. Otherwise, you’ll make these weird proteins and the cell could be very toxic. So, you have to overcome this sort of desire of the cell to stop there. So, ataluren does overcome that. It doesn’t restore it to a wild-type level, but we think it restores it enough to stabilize the disease, and that’s what we’ve shown in our clinical trials to date. So, it just tricks the cell a little bit to make a full-length protein.


How do you envision the future for people with DMD?

I think it’s very optimistic. I think that there are a lot of companies who are making drugs for DMD now. I think there’s ataluren for the read-through population. I think there’s exon skipping that’s coming. Other people are working on things that, other proteins that you can up-regulate to replace dystrophin like utrophin. They’re doing that. So, I think there’s a lot of, there’s a nucleus of people that are basically working from many different directions to identify treatments for DMD. So, I think it’s pretty optimistic, even for kids now. I think it will just get better. But I think I’m fairly optimistic.


Actions to help access to ataluren in Canada

There are a couple of things that you can do right now to help us promote access to ataluren in Canada. Here are three actions that you take right now that will help the DMD community:

1- Be aware of your genetic profile. If you don’t have it, ask your doctor.

2- Get in touch with us. E-mail us, follow-us. We’ll be documenting government approval processes

3- Spread the word. Share our content, share pertinent information, and tell your stories.


Up next:

Our next portrait: Joanne Donovan, Chief Medical Officer and Senior Vice President, Clinical Development, Catabasis Pharmaceuticals

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We thank the PTC Therapeutics team, who received us with open arms to conduct a series of interviews.

We thank Allain Lagadic and Daniel Cooper


PTC Therapeutics

Ataluren (Translarna™)

ACT DMD Clinical Trial of Translarna™ (ataluren)



Portrait of Duchenne – Utrophin Modulator

Michelle Avery, PhD

Director, Investor Relations at Summit Therapeutics plc

In this second interview of our series “Portrait of Duchenne,” La Fondation La Force talks with Michelle Avery, the Director of Investor Relations for Summit Therapeutics plc. She also heads patient relations and public relations. Michelle Avery answers our question about utrophin modulators – a potential disease-modifying approach to treat all patients with DMD.

Our journey at La Fondation La Force travels the road of discovery with families, researchers, pharmaceutical companies and more. Our mission is finding the best new experimental treatments and the most promising research for children and adults with Duchenne muscular dystrophy (DMD). In November 2016, we went to the 14th Action Duchenne International Conference in London, UK, to meet with the international DMD community on your behalf.  We hope this series of interviews will bring hope and inspiration to Canadian families.

What is utrophin?

The human body naturally produces utrophin, a protein, when muscle first forms or when it’s repairing. As muscle matures, dystrophin replaces utrophin. However, in people with DMD, dystrophin does not function properly. Utrophin is functionally and structurally similar to dystrophin.

In the video, Michelle Avery answers our questions about utrophin modulators


  • Utrophin modulation is:

R: Utrophin is a protein very similar to dystrophin. Utrophin is present when a muscle is first forming or when it’s repairing. But then, for whatever reason, it’s turned off, and dystrophin comes in to take its place. Now, this is still in place in the boys with DMD… They have a lot of utrophin being made, as the muscles are repairing, but they also have the signal to turn it off. So what we’re trying to do is keep that utrophin turned on. As the muscles mature, they can have utrophin instead of dystrophin.

  • Where will this treatment be available first?

R: Right now, our development program… we’re considering a global program… Regulatory-wise, the U.S. usually comes along first and more rapidly than other countries, but we have a collaboration with Sarepta Therapeutics for Europe… They’re going to do a great job… They’ve had a lot of experience in DMD so far, so we’re excited to use their expertise, and they will be taking over in Europe and potentially in Latin America as well. There are some countries in Latin America where they have that option to sell our drug.

  • Can utrophin replace dystrophin?

R: We believe that utrophin can replace dystrophin, and this is based on a lot of work that we’ve done in mice, where we’ve seen that these mice can look much like “normal” when they have utrophin in the place of dystrophin. Utrophin itself is just a little bit smaller than the dystrophin, and it is missing a couple of different bonding. What we know from studies with patients with Becker’s is that if they’re missing the part of dystrophin that is missing in utrophin, these patients seem to do pretty well. So that’s encouraging that you don’t necessarily need all of the parts of dystrophin to have a more normal muscle function.

  • How do you see the future for the DMD community?

R: It’s very exciting work. We’re hoping this is, like, the first trial that lets us know whether or not this has a chance to work in patients, and we’re hopeful… It seems like it makes sense from a scientific perspective.


Clinical trial information updated: PhaseOut DMD

PhaseOut DMD is a Phase II clinical trial evaluating ezutromid, a utrophin modulator, in patients with DMD. This 48-week, open-label study is ongoing in the U.K. and USA. The study plans to enrol approximately 40 patients by mid-2017.

In addition to PhaseOut DMD, Summit Therapeutics plc plans to conduct a randomized, placebo-controlled trial specifically designed to support accelerated and conditional approvals for ezutromid in the USA and Europe. If PhaseOut DMD yields positive interim data, planning of this trial would begin after the 24-week data are reported.

For more information about the PhaseOut DMD clinical trial of ezutromid: Utrophin Trials   –  Clinical trials

For more information about utrophin, you  can also read our previous article: Utrophin production might be a good option for people with DMD

More about Summit PLC Therapeutics

Summit plc is e a clinical-stage drug discovery and development company advancing innovative therapies to significantly advance the current standard of treatment for serious unmet medical needs. Their strategy focuses on two therapy areas: Duchenne muscular dystrophy, a fatal genetic muscle-wasting disease, and the infectious disease caused by the bacteria C. difficile.


Up next:

Our next portrait: Exon Skipping with Georges Dickson

To receive the next interview in our series “Portrait of Duchenne,” please subscribe to our newsletter.



We thank the Action Duchenne UK team, who received us with open arms and gave us access to all key speakers at their conference. Because of their generosity, we can spread this hopeful information to the Canadian DMD community.


To know more about the Action Duchenne conference:


Special Thanks to Daniel K Cooper and Allain Lagadic

  • 2018 September  > Summit Therapeutics ends development of ezutromid therapy for DMD after trial failure. Read more here. 
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Utrophin production might be a good option for people with DMD

Utrophin could potentially replace dystrophin. In people with Duchenne muscular dystrophy (DMD), dystrophin does not function properly. Numerous media outlets have recently reported many exciting developments in the search for new treatments for Duchenne muscular dystrophy (DMD). Science, medicine, and technology are uniting to create significant results. This article is the first in a new series to shed light on promising, experimental treatment options. This first article will feature utrophin production.

What is utrophin?

The human body naturally produces utrophin, a protein, when a muscle is first forming or when a muscle is repairingAs a muscle matures, dystrophin replaces utrophin. However, in people with Duchenne muscular dystrophy (DMD), dystrophin does not function properly.

Utrophin is functionally and structurally similar to dystrophin. Preclinical trials that have stimulated sustained utrophin production have shown that it could potentially replace dystrophin in people with Duchenne muscular dystrophy (DMD). The replacement of dysfunctional dystrophin with functional utrophin might have a highly positive impact on muscle performance.

Summit Therapeutics believes that utrophin may slow or even stop the progression of DMD.

More information: PPMD  –  Wikipedia  – NCBI

What is ezutromid?

Ezutromid is an utrophin modulator.

It is an orally administered, small molecule, experimental drug, in development by Summit Therapeutics.

More information

How does it work?

Ezutromid stimulates the body to sustain production of utrophin.

This experimental therapy has the potential to work in people with all genetic profiles of Duchenne muscular dystrophy (DMD). Given that it doesn’t depend on a specific genetic profile, this treatment may be suitable for 100% of people with DMD.

Clinical Trial

Summit Therapeutics just announced that the first patients have been enrolled into trial sites in the US into PhaseOut DMD. Summit Therapeutics will be making updates about additional US sites and contact details to the clinicaltrials.gov record (https://clinicaltrials.gov/ct2/show/NCT02858362). As a reminder, PhaseOut DMD is a 48-week, open-label (meaning all participants receive ezutromid) Phase 2 trial, is ongoing in the UK and the US. Enrolment of approximately 40 patients continues, and they expect to complete trial enrolment in the second quarter of 2017.

For more information about PhaseOut DMD clinical trial of ezutromid: Utrophin Trials   –  Clinical trials

What’s the regulatory status of ezutromid?

Ezutromid is an experimental drug candidate in Phase 2 clinical trialThe U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have granted Orphan Drug designation to ezutromid. Orphan drugs receive a number of benefits, including additional regulatory support and a period of market exclusivity after marketing approval. In addition, the FDA has granted ezutromid both Fast Track and Rare Pediatric Disease designations.

Recently, Summit Therapeutics Plc applied to the MHRA and FDA regulatory authorities to proceed with the planned extension of PhaseOut DMD for patients currently enrolled in the trial. The extension phase is expected to last until ezutromid either receives marketing approval in relevant countries or its development is discontinued.

In addition to PhaseOut DMD, they plan to conduct a randomised, placebo-controlled trial designed with the potential to support accelerated and conditional approvals for ezutromid in the US and Europe. It is anticipated that this trial would start after positive interim data from PhaseOut DMD.

Summit to Extend Ongoing PhaseOut DMD Clinical Trial of Ezutromid in Patients with DMD: Press Release 

How is ezutromid administered?

Ezutromid is given orally, as a liquid.

Muscular Dystrophy News

A word from the manufacturer

“The Rare Pediatric Disease designation builds upon the Fast Track and Orphan Drug designations, which the FDA has already awarded to ezutromid, recognizing a significant unmet medical need in the treatment of DMD,” says Glyn Edwards, Chief Executive Officer of Summit.

“We plan to leverage these regulatory advantages in the continued clinical development of ezutromid, which is currently in Phase 2 clinical trial called PhaseOut DMD, to bring ezutromid to patients in need as quickly as possible.”

For more information about ezutromid click here


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New treatments for Duchenne muscular dystrophy: a stalled process

Initial Duchenne muscular dystrophy diagnoses usually come about around age 4 or 5 years, mostly in young boys. Duchenne muscular dystrophy often referred to as “DMD”, is the most severe form of muscular dystrophy.

It is a degenerative disease that gradually weakens every muscle in the body, and that inevitably leads to premature death when afflicted kids reach their twenties. The corticosteroid-type treatments currently available – used for anti-inflammatory purposes – can prolong certain muscle functions; however, the side effects of these products are devastating in the long run!

A difficult approval process for effective treatments

For the first time in the history of Duchenne muscular dystrophy, innovative treatments that directly address the genetic causes of the disease are currently undergoing the FDA (Food and Drug Administration) approval process in the United States: Ataluren (PTC Therapeutic), Eteplirsen (Sarepta Therapeutics) and Drisapersen (BioMarin).

Ataluren is used in cases where on children happen to have a so-called “nonsense” genetic mutation, while the action of the other two, eteplirsen and drisapersen, has to do with the “exon skipping” principle.

Earlier this year, Sarepta Therapeutics, the pharmaceutical company developing Eteplirsen, was informed that there would be a delay in the process; the most recent news is that the matter is to be re-evaluated by a committee. Less than a month ago, it was PTC Therapeutics’ turn to be told, much to their surprise, that certain elements of information were missing, despite the fact that its drug, Ataluren, had been approved in Europe (May 2014 – read more).

Undue delays for children who have no time to wait

The FDA’s decisions influence those of all other jurisdictions. Failure to get approval for these pioneering treatments could have the effect of discouraging other pharmaceutical companies from developing alternative treatments for Duchenne muscular dystrophy. Worthy of mention is the fact that, although the data is currently deemed insufficient by the authorities, clinical trials have clearly demonstrated the positive effects of these treatments on children, with very few side effects.

These delays sometimes cause pharmaceutical companies to lose significant value in the stock market, which is unfortunate. But even worse are the years of life the kids lose due to a blocked approval process that prevents them get the treatment they need.

In fact, the community has but one choice, and that is to take action… Otherwise, no treatment!

Knowledge before action!

Of course, we do not at present have all the answers: Team La Force’s mission is to develop expertise in the field and broadcast to the Canadian Duchenne Muscular Dystrophy community any relevant information pertaining to access to treatment.

We’ve given ourselves the mandate to inform the DMD community because we believe that disseminating knowledge is a great way to change things. With this in mind, we are announcing with great pleasure that La Force will be attending the FDA-AdComm conference to be held in Washington in late April. Our goal is to acquire as much knowledge as we can about the North American treatment approval processes and keep you informed.

What should you do as a parent of a child afflicted with Duchenne muscular dystrophy?

If your child is suffering from DMD, we suggest you do the following:

  1. In consultation with competent medical personnel, determine your child’s specific genetic condition, find out the exact reason why he/she is afflicted with DMD; it will guide you as to what treatments, existing or in development, are appropriate to his/her situation;
  2. Learn about these treatments and work to get access to them: it’s a good idea to consult with us, because, with time we’ve learned a lot on the subject matter;
  3. Communicate with the people around you and share the information in order to raise awareness about the disease, about the availability of new treatments and about the long and laborious approval processes;
  4. Follow us on the web and on social networks in order to stay abreast of developments and benefit from the support of the DMD community.

Link about New treatments for Duchenne muscular dystrophy


Sarepta Therapeutics

Eteplirsen – The Facts About Eteplirsen – Uptick Analyst – FDA Approval Status – FDA: Please accept Sarepta’s New Drug Application (NDA) for Eteplirsen



Drisapersen – FDA Approval Status (Drisapersen (Kyndrisa) – FDA Decision on Drisapersen for Duchenne Muscular Dystrophy


PTC Therapeutics

Fierce Biotech – PTC: With no evidence of Duchenne MD efficacy, FDA barred regulators’ doors to ataluren

Results from Phase 3 ACT DMD Clinical Trial of Translarna™ (ataluren) – Ataluren at Health Canada – Recommandation pour le remboursement NICE (UK)


FDA Draft Guidance on Duchenne

The Wall Street Journal