About Utrophin

Utrophin is a naturally occurring protein that is functionally and structurally similar to dystrophin. Utrophin is produced during the early stages of muscle fibre development but is switched off in maturing muscle fibres, at which point dystrophin is produced to perform the same functional role. When a muscle fibre is damaged, utrophin is also produced during the early stages of the repair mechanism.

We aim to modulate, or change, how utrophin is produced in boys and men with DMD. Our utrophin modulation approach aims to use small molecule drugs to maintain the production of utrophin to compensate for the absence of dystrophin in boys and men with DMD and so protect healthy muscle function. A significant advantage of utrophin modulation is that it is independent of the underlying genetic fault and therefore has the potential to treat all patients with DMD. We also believe it could be complementary to other DMD treatment approaches.

View our recent webinar on utrophin, PhaseOut DMD and our work in muscle biomarkers here.

about
Depiction of the role of utrophin and dystrophin in normal muscle and DMD fibres and the potential role of utrophin modulation in DMD fibres.

Clinical Trials

Clinical trials are a part of a carefully planned and legally required process to move from the identification of a potential new drug in the laboratory to being available on the market. Clinical trials mark the beginning of testing a product candidate in humans and are only conducted after undertaking appropriate experiments in the laboratory to determine if such a candidate is suitable for testing in humans for the disease being studied.

There are several steps to the clinical trial process, called “phases.” Each phase is designed to answer specific questions that help the researchers decide whether or not the product candidate should continue in development.

Phase 1

Phase 1 is the first step, and the primary goal of this phase is to determine the safety of the medication being tested. Phase 1 is usually conducted in a small group of healthy volunteers, but can also include patients with the disease for which the product candidate is being tested.

Phase 2

If Phase 1 trials are successful, the product candidate moves to Phase 2. Phase 2 trials are designed to evaluate the efficacy of a product candidate in the patients with the disease for which the product candidate is being tested. In addition, the Phase 2 trial will continue to assess the safety of the product candidate. These trials are often slightly larger than Phase 1 trials.

Phase 3

If the Phase 2 trials are successful, the product candidate moves to Phase 3. The objective of Phase 3 is to confirm the efficacy and safety findings of Phase 2 in an even larger group of patients with the disease for which the product candidate is being tested. If there is a standard of care treatment for the disease being studied, the new product candidate will often be compared to the efficacy and safety of that standard of care treatment. Regulatory agencies use the findings from all of these phases to decide whether the product candidate should be approved for use in a specific disease indication outside of clinical trials.

Our lead utrophin modulator candidate, ezutromid, is currently being evaluated in the following clinical trial:
– PhaseOut DMD

PhaseOut DMD

PhaseOut DMD is a Phase 2 clinical trial designed to evaluate the safety and efficacy of ezutromid. PhaseOut DMD aims to provide proof of concept, or evidence that ezutromid could modulate utrophin and lead to clinical benefit.

This will be evaluated though a range of measures including looking at the amount of fat that infiltrates into muscle using a technique called magnetic resonance imaging (MRI), as well as measuring utrophin protein and muscle fibre regeneration in muscle biopsies. The 48-week open-label trial has completed enrolment of 40 boys ranging in age from their fifth to their tenth birthdays at sites in the UK and in the US.

Endpoints

The primary endpoint of the trial is the change from baseline in magnetic resonance imaging parameters related to fat infiltration and inflammation of the leg muscles.

Additional endpoints include measuring utrophin protein and muscle fibre regeneration levels from muscle biopsies, safety and pharmacokinetic measures and exploratory functional measures including the six-minute walk test, North Star Ambulatory Assessment and patient reported outcomes.

  • Mechanism

    • Utrophin protein
    • Muscle fibre regeneration
  • Muscle Health

    • Magnetic Resonance Imaging (MRI) primary endpoint
    • Serum markers
  • Function

    • Six minute walk distance
    • North Star Ambulatory Assessment

Clinical Trial Sites

uk-map
  • Birmingham, UK

    Birmingham Heartlands Hospital
  • Bristol, UK

    Bristol Children's Hospital
  • Cambridge, UK

    Addenbrooke’s Hospital
  • Liverpool, UK

    Alder Hey Children’s Hospital
  • London, UK

    Great Ormond Street Hospital
  • Manchester, UK

    Manchester Royal Infirmary
  • Newcastle, UK

    Newcastle University Medical Center
Web
  • Aurora, CO, US

    Children's Hospital of Colorado
  • Orlando, FL, US

    Nemours Children's Hospital
  • Boston, MA, US

    Boston Children's Hospital
  • Cincinnati, OH, US

    Cincinnati Children's Hospital
  • Los Angeles, CA, US

    UCLA-David Geffen School of Medicine
  • Portland, OR, US

    Oregon Health Sciences University
  • Philadelphia, PA, US

    Children's Hospital of Philadelphia
  • Nashville, TN, US

    Vanderbilt University
  • Salt Lake City, UT, US

    University of Utah Hospitals and Clinics
FAQs

1. What is utrophin?

Utrophin is a naturally occurring protein that is functionally and structurally similar to dystrophin. Utrophin is produced during the early stages of muscle fibre development and then gradually switched off in maturing muscle fibres as dystrophin production steadily increases to perform the same functional role. When a muscle fibre is damaged, utrophin is produced during the stages of the repair. Our utrophin modulation approach aims to use small molecule drugs to maintain the production of utrophin to compensate for the absence of dystrophin in DMD patients and so protect healthy muscle function.

2. The lead utrophin modulator is ezutromid. What is this and how does it work?

Ezutromid is a small molecule investigational drug that is administered orally. We believe ezutromid could maintain muscle health by keeping production of utrophin switched on to substitute for dystrophin (in mature muscle fibres).

3. How many clinical trials has ezutromid completed and what have you found in these trials?

Ezutromid has completed Phase 1 clinical trials in healthy adult volunteers, for a total of about 100 people, and Phase 1 clinical trials in patients with DMD, for a total of 22 individual patients. Throughout these trials, ezutromid has been generally well-tolerated. Thus far, the most frequent adverse event is pale stools caused by the unabsorbed product candidate. We have also found that ezutromid is best absorbed by patients on a balanced diet of fats, carbohydrates and proteins, who take a small glass of full fat milk with ezutromid. With this regimen, we believe that all patients who are administered ezutromid may be able to sustain utrophin protein expression and that could lead to clinical benefit.

4. At what stage of development is ezutromid ? Where will its clinical trials take place?

Ezutromid is being tested in a Phase 2 clinical trial called PhaseOut DMD. The trial is taking place in the UK and in the US.

5. How long will the PhaseOut DMD trial last?

PhaseOut DMD is a 48-week trial. Patients enrolled in the trial have the option to participate in an extension phase once the 48 week treatment phase has completed. The extension phase is expected to last until ezutromid either receives marketing approval in the relevant country or its development is discontinued.

6. Who will be able to participate in the PhaseOut DMD trial?

PhaseOut DMD trial has completed enrolment of 40 boys at sites in the UK and US.

7. Are there any restrictions on the dystrophin mutation in your trials?

There is no restriction on mutation type, as utrophin modulation has the potential to treat all patients with DMD, regardless of the underlying mutation to dystrophin. There are though other inclusion and exclusion criteria that a patient will need to meet in order to participate in the clinical trial.

8. What endpoints are in the PhaseOut DMD trial?

The primary endpoint of the open‐label trial is the change from baseline in magnetic resonance imaging parameters related to fat infiltration and inflammation of the leg muscles. Additional endpoints include utrophin protein and muscle fibre regeneration measurements from muscle biopsies, safety and pharmacokinetic measures and exploratory functional measures including the six‐minute walk test, North Star Ambulatory Assessment and patient reported outcomes.

9. Why do you need to collect biopsies?

Our aim is to show that ezutromid treatment changes where utrophin is located in a patient’s muscles and also changes the amount of regenerating muscle. In order to study that, we need to look at a muscle biopsy before administering ezutromid and another after taking ezutromid for a period of time.

10. How will you know if ezutromid works?

We are looking at many different endpoints to examine the efficacy of ezutromid. Each one of those efficacy endpoints could signal that ezutromid is having a positive effect on patients, but we would need to see consistent data on that endpoint within the trial population to determine if the effect is related to treatment with ezutromid. From there, we would likely need to conduct a larger, placebo-controlled clinical trial to confirm our findings. If we believe the data support a regulatory filing for ezutromid, we would then present them to the regulatory authorities, which would decide if there is enough evidence of safety and efficacy for approval.

11. Why should I consider participating in future clinical trials?

While no personal benefit can ever be guaranteed by participation in a clinical trial, there are other potential benefits, including allowing you to play an active role in your healthcare and helping others by contributing to the better understanding of DMD.

12. How can I get involved in a clinical trial?

To get involved in any DMD clinical trials, start by expressing your interest in participating in a trial with the physician who coordinates your or your son’s DMD care and ensure you are in the DMD registry in your country (see http://www.treat‐nmd.eu/dmd/patient‐registries/dmd/ for reference). Once a clinical trial site is open for recruitment, you can contact the sites directly to ask about enrolling in the trial.

13. Where can I find more information about your clinical trials?

More information about the trial is available on www.clinicaltrialsregister.eu and www.clinicaltrials.gov.

14. Is it possible to get access to ezutromid under compassionate use?

At this time, we do not provide access to ezutromid outside our clinical trials. Ezutromid is an experimental drug, and we are focused on finding out as quickly as possible whether treatment with ezutromid may provide clinical benefit for patients with DMD. We believe this will be achieved through evaluating its potential efficacy and safety in well-designed, controlled clinical trials.

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Contacts:

Michelle Avery
e: michelle.avery@summitplc.com
t: +1 617 225 4455

UK/European families:
t: +44 (0)1235 443939