An Update for the Duchenne Community


We are sharing the following update from Sarepta Therapeutics.


Sarepta Therapeutics is updating the Duchenne community regarding recent changes to the Phase III confirmatory clinical study, ESSENCE (Study 4045-301), as posted on [Identifier: NCT02500381]

ESSENCE will serve as a confirmatory study for eteplirsen if it is granted accelerated approval. Post-marketing confirmatory studies are a requirement for drugs that are granted accelerated approval in order to verify the clinical benefit of the drug.

Additionally, we believe that data generated from the ESSENCE study will serve as a foundation to the advancement of our future DMD development programs and to demonstrating the potential safety and efficacy of SRP-4045 and SRP-4053 in boys with mutations amenable to skipping exons 45 and 53, respectively.

We acknowledge the community’s concerns regarding a 96 week placebo-controlled trial and hope to provide clarity regarding recent changes to the clinical study design in this communication.

Why is Sarepta conducting a placebo-controlled trial?

In addition to fulfilling confirmatory study requirements for eteplirsen, we believe that following FDA guidance will provide the most efficient pathway to approval for SRP-4045 and SRP-4053.

Why has the trial been extended from 48 weeks to 96 weeks?

The primary endpoint for the ESSENCE study is 6MWT. Data reported from Sarepta’s “201/202” study revealed that a statistically significant divergence (or separation) in 6MWT between patients on eteplirsen vs. patients in the external control who were not receiving eteplirsen, was not demonstrated at 48 weeks of treatment.

As stated in the FDA draft guidance: “efficacy studies of 18 to 24 months’ duration may substantially increase statistical power, while only modestly increasing overall development time.” We believe that extending this trial to 96 weeks will increase the likelihood of meeting the primary endpoint and generating data that may lead to broader access across the Duchenne populations amenable to these investigational candidates.

What is an interim analysis and what are the implications?

An interim analysis provides an opportunity to look at data at a pre-defined point in time. Sarepta has included a planned interim analysis of the 6MWT in the ESSENCE study when 75% of the study population have reached 48 weeks of participation in the study. A Data Safety Monitoring Board (DSMB) will review these interim data collected and make a recommendation based on their findings. At that point, the study may:

• continue as planned

• be stopped early due to positive efficacy results

If the trial is stopped early due to positive efficacy results, patients in the treatment arm will continue to receive investigational treatment and those in the placebo arm of the study will roll over onto active investigational treatment with either SRP-4045 or SRP-4053. It is important to point out that if the study is stopped early due to positive results, this potentially would be a shorter time period than a standard 48 week study where you would not look at the data until every patient had completed the 48 week time point.

Why has the age range changed from 7-16 years to 7-13 years?

Studies can fail if they are not designed appropriately. We need to use the most current understanding of this complex disease to ensure the data are interpretable.

Based on our review of Duchenne natural history data, some young men over the age of 13 who walk further than 300 meters on a 6MWT seem to behave differently than what is typically observed in the progression of the disease. Because of the less predictable disease course in such patients, they could introduce variability that would make it harder to see a difference between the patients receiving treatment and the patients receiving placebo and thus could jeopardize the overall results of the study. By studying a homogenous (or, very similar) population of patients, we believe there is an increased chance that the primary endpoint of the study will be met.

When will the study start enrolling?

We will work with participating trial sites and patient advocacy organizations to notify the patient community when sites are open for enrollment. You may also check [Identifier: NCT02500381] for the most up-to-date information on the enrollment status of study sites.

What can the community do?

Stay informed by keeping in touch with your doctor and other members of the community. Sarepta will be working with ESSENCE investigators, study staff, and advocacy organizations to expedite enrollment of the study and to provide updates as they become available.

Genetic testing is always required to determine eligibility for investigational exon-skipping drugs targeted to specific mutations. We recommend that patients and families who have general questions about genetic testing or genetic test results contact their physician or a genetic counselor.

Sarepta remains committed to the Duchenne community and thanks Duchenne patients and families, clinical investigators, and advocacy organizations for your support of and participation in the clinical trial process. Kindly submit your questions regarding the ESSENCE study via email to

Forward Looking-Statements:

This patient community update contains various forward-looking statements regarding regulatory, clinical and other Sarepta matters. Each forward-looking statement contained in this update is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statement. Applicable risks and uncertainties include those identified under the heading “Risk Factors” in Sarepta’s Quarterly Report on Form 10-Q for the Quarter ended March 1, 2016 ( 10q_20160331.htm) and Annual Report on Form 10-K for the year ending December 31, 2015 ( and other documents filed by Sarepta with the Securities and Exchange Commission.

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