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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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The approval process for new drugs

When you’re suffering from a fatal (orphan) disease for which there is no cure, such as Duchenne muscular dystrophy, each year, month, day, hour and second that separates you from a potential treatment is VITAL.

Nowadays, in an era when science and technology are advancing at the speed of light, new forms of treatment for Duchenne muscular dystrophy, about to be approved to represent real hope. However, these new forms of treatment must go through an approval process that takes between 2 and four years before becoming available to patients.

When rare diseases are involved, patients should be involved in this process so that it occurs as quickly as possible and that the medication is reimbursed by all provinces across Canada.

Here is a brief overview of the process.




The patient can access treatment before the end of the process through a special access program, but the treatment is not reimbursed.

In Canada, Health Canada is responsible for authorizing the use of a drug. What follows is the process that pharmaceutical companies sponsoring the development of a new drug must adhere to:

Step 1> The developer of the drug submits an application to Health Canada in order to obtain permission to conduct clinical trials in Canada.

Step 2> If the review of clinical trials shows that the drug has a potential therapeutic value that surpasses the risks associated with taking the drug, the pharmaceutical company may choose to submit a New Drug Submission to the HPFB (Health Products and Food Branch) of Health Canada.

Step 3> Submission of a “New drug submission” to the Branch, who performs a thorough review of the information submitted.

Step 4> If findings reveal that the benefits outweigh the risks, the Branch issues a Notice of Compliance and a Drug Identification Number (DIN) which allows the company to market the drug in Canada.



(After obtaining the “DIN” marketing number)

Let’s now look at how things work in the provinces and territories. First, it’s worth mentioning that each province and territory in Canada has a drug reimbursement system of its own.

Process for QUÉBEC

TIMELINE: ONE YEAR (approximately)


One can make an exception request that provides for reimbursement of treatment on an individual basis.

In Québec, this process is governed by the INESSS (National Institute of excellence in health and social services).

Step 5> The pharmaceutical company files an application with the Institute (INESSS). Applications for registration of drugs are analyzed by INESSS professionals and by the Standing Scientific Committee. This application can be filed only after obtaining the (DIN).

Step 6> INESSS publishes a Notice to the Minister, that contains recommendations relating to the products evaluated by its department, and explains the reasons for product acceptance or rejection, in accordance with governing legislation.

Step 7> The RAMQ updates the list of insured drugs. The last update took place on February 8, 2016.




In the other provinces and territories, the process is governed by the Common Drug Review Program (CDR) and the Pan-Canadian Drug Purchasing Alliance – PCDPA

TIMELINE: 1 YEAR + … (slightly longer than in Québec)

Step 5> Submission to the CDR. Submissions are necessary for public reimbursement in Canada with any new drug. The CDR submissions affect all provincial reimbursement programs (except Quebec).

Step 6> The CDR conducts a rigorous and objective evaluation of the clinical and economic evidence, and makes recommendations to federal, provincial and territorial government public drug insurance plans, except Québec which administers its own review process (INESSS).

Step 7> After the drug review, the CDEC (Canadian Drug Expert Committee) may recommend the inclusion of a drug in the participating drug plans.

Step 8> The participating drug plans then make a final decision on the refund policy for this drug: each province and territory (except Quebec) chooses to reimburse patients or not for the drug.


CRISPR-cas9 … Genetic engineering offers real hope of advancement

The year 2015 ended with the announcement of great news for the DMD community. Indeed, the scientific community has been voicing much enthusiasm at the discovery of a genetic engineering technique that will eventually help us with a wide array of things, such as protecting certain endangered species, stopping malaria and curing diseases!

Genetic “cut and paste”

The event is of such scientific importance that Science magazine awarded the title of a scientific breakthrough of the year to the genetic engineering technology referred to as CRISPR/cas9. La Presse + published an interesting and informative article on the subject in its January 17, 2016, edition.

Derived from a bacterial defence mechanism, a new gene suppression and insertion technique is spreading like wildfire in laboratories everywhere. Thanks to its high targeting accuracy, CRISPR-cas9 is by far the most effective technique to correct DNA defects. It’s described as a “molecular kit” of sorts, a clever and complex toolkit that enables us to perform “cut and paste” operations in the DNA of living things.

This technology works as follows:

  • The CRISPR component – a type of gene sequence found naturally in certain organisms, including viruses – can recognize a specific genome sequence, that is to say, go to the place where lies the defect responsible for the disease.
  • The Cas9 component acts as a pair of scissors and can “cut” in the DNA at a specific location, i.e., where action must be taken.
  • From here, one can either choose to remove a genetic mutation or insert a fix for the faulty gene.
  • Using its normal DNA repair mechanisms, the cell will then naturally reattach the strands.

The latest results obtained in mice demonstrate the CRISPR method’s potential for correcting certain genetic abnormalities after birth.

An encouraging step in the fight against DMD

As we know, DMD is the result of an error in the “writing” of the gene responsible for producing dystrophin. In people suffering from Duchenne muscular dystrophy, the dystrophin gene has undergone a genetic mutation: the gene is badly written, the cellular machinery expected to read it cannot do it, and as a result, the protein is simply not produced.

Researchers have undertaken to use CRISPR/Cas9 to remove the mutated part of the gene. By erasing the illegible component blocking the genetic material’s decoding process and introducing a proper genetic sequence, researchers have restored the production of dystrophin, which is essential to the proper functioning of the muscle.

To spread their molecular kit in all of the body’s cells of the researchers found a way to put it on board of viruses that have a particular attraction to muscle cells. They then injected this mixture into diseased mice. After a few weeks, the muscles of these rodents began synthesizing dystrophin, a substance they were previously unable to produce…

Cautiously excited…

As exciting as the news of this extraordinary discovery is, we are still far from our common goal: it must be kept in mind that testing has only been performed on mice at this time, and researchers warn that the real challenge will be to transpose this in humans and potentially have to deal with an immune response from the patient.

That being said, it will be extremely interesting to see where it takes us!

A few relevant links: