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.

Using small molecule drugs, Summit aimed to modulate, or 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.

In June 2018, we announced that PhaseOut DMD, our Phase 2 clinical trial of the utrophin modulator ezutromid, did not meet its primary and secondary endpoints. We have therefore made the difficult decision to discontinue development of ezutromid. Read the press release 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, has completed a Phase 2 clinical trial called PhaseOut DMD.

PhaseOut DMD

PhaseOut DMD wasa Phase 2 clinical trial designed to evaluate the safety and efficacy of ezutromid. PhaseOut DMD aimed to provide proof of concept, or evidence that ezutromid could modulate utrophin and lead to clinical benefit. PhaseOut DMD did not meet its primary of secondary endpoints. The clinical trial results provided no evidence that ezutromid was having a meaningful effect on slowing DMD progression. We therefore cannot support further development of ezutromid. We are now working with our clinical trial investigators to bring the PhaseOut DMD clinical trial and its associated extension phase to a close. Patients in PhaseOut DMD should contact their study doctors for more information.

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.

2. 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. Ezutromid has also completed a Phase 2 clinical trial, called PhaseOut DMD, which enrolled 40 patients. Throughout these trials, ezutromid has been generally well-tolerated. PhaseOut DMD did not meet its primary or secondary endpoints. Since it was determined that ezutromid did not have a meaningful effect on slowing DMD progression, its development has been discontinued. We are now working with our clinical trial investigators to bring the PhaseOut DMD clinical trial and its associated extension phase to a close. Patients in PhaseOut DMD should contact their study doctors for more information.

3. At what stage of development is ezutromid?

Ezutromid completed a Phase 2 clinical trial. The trial did not meet the primary or secondary endpoints, and ezutromid’s development has been discontinued.

4. My son is still in the trial - what should I do?

We are working with our clinical trial investigators to bring the trial and extension phase to a close, including any patients who have been enrolled into the additional cohort of the trial that was opened in March 2018. Patients in PhaseOut DMD should contact their study doctors for more information.

5. What endpoints were in the PhaseOut DMD trial?

The primary endpoint of the open‐label trial was changes from baseline in magnetic resonance 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.

6. Why did you need to collect biopsies?

Our aim was 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, looked at a muscle biopsy before administering ezutromid and another after taking ezutromid for a period of time.

7. Will I have access to my/my child's data?

Please view our data sharing policy here.

8. Where can I find more information about PhaseOut DMD?

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

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

As we have decided to discontinue the development of ezutromid, we cannot support any compassionate use.

Update on Ezutromid

After reviewing the top-line results of PhaseOut DMD, we have made the difficult decision to discontinue the development of ezutromid.

We recognize that this decision will be disappointing for the Duchenne community, but the data from PhaseOut DMD were clear that ezutromid, while well-tolerated, did not provide a benefit to patients with DMD.

These results are not what we had hoped for, and certainly not what we had expected based on the encouraging interim results from PhaseOut DMD. But, they provide a clear answer to the important scientific question of ezutromid’s effect in DMD. The results provided no evidence that ezutromid is having a meaningful effect on slowing DMD progression. We therefore cannot support further development of ezutromid. We are now working with our clinical trial investigators to bring the PhaseOut DMD clinical trial and associated extension phase to a close. Patients in PhaseOut DMD should contact their study doctors for more information.

We sincerely thank the patients, families and clinical trial sites who have been involved in all of our clinical trials of ezutromid. We plan to explore ways that the information gathered as part of PhaseOut DMD can be made available to support other research activities in DMD for the benefit of the entire community.

We are also grateful for the support that we’ve had from patient organizations worldwide in the development of ezutromid.

We believe that the future of Duchenne research is bright. There are numerous clinical trials and research studies taking place in this field, and there is hope on the horizon for all those living with DMD.

If you have further questions, please contact Michelle Avery, PhD, our Director of Patient Engagement, at michelle.avery@summitplc.com.

Sincerely,

Glyn Edwards, CEO of Summit