Sarepta Therapeutics is focused on developing first-in-class RNA-based therapeutics to improve and save the lives of people affected by serious and life-threatening rare and infectious diseases. Our diverse pipeline includes eteplirsen, our lead program for Duchenne muscular dystrophy, as well as potential treatments for some of the world's most lethal infectious diseases. We aim to build a leading, independent biopharmaceutical company dedicated to translating RNA-based science into transformational therapies for patients who face significant unmet medical needs.
|Sarepta Therapeutics Announces Eteplirsen Demonstrates a Continued Benefit on Walking Test Through 84 Weeks in Phase IIb Study in Duchenne Muscular Dystrophy|
After 84 weeks, patients in the 30 mg/kg and 50 mg/kg dose cohorts who were able to perform the 6MWT (modified Intent-to-Treat or mITT population; n=6) showed a statistically significant treatment benefit of 46.4 meters (p≤0.045) when compared to the placebo/delayed-treatment cohort (n=4). The eteplirsen-treated patients in the mITT population demonstrated less than a 6 percent decline (20.5 meters) from baseline in walking ability. After experiencing a substantial decline earlier in the study, the placebo/delayed-treatment cohort also demonstrated stabilization in walking ability from Week 36 through 84, the period from which meaningful levels of dystrophin were likely produced, with an increase of 3.3 meters over this timeframe. These analyses were based on the maximum 6MWT score when the test was performed on two consecutive days.
"We now have demonstrated stability of walking for over a year and a half in the original eteplirsen treatment cohort in boys who are now 11 years old on average, an age when many DMD boys have lost the ability to walk," said
Through 84 weeks, eteplirsen was well tolerated and there were no clinically significant treatment-related adverse events, no serious adverse events, hospitalizations or discontinuations.
One boy in the placebo/delayed-treatment cohort was not able to perform the 6MWT at the Week 84 clinic visit due to a physical injury unrelated to treatment, and therefore had no 6MWT data captured at the Week 84 time point. The boy has recovered from the injury, continues to be ambulatory and is expected to be evaluated on the 6MWT at future clinic visits.
Across all patients in the eteplirsen and placebo/delayed-treatment cohorts (Intent-to-Treat or ITT population), there is evidence of continued stabilization on clinical laboratory tests, echocardiograms, pulmonary function tests and measures of muscle strength.
Summary of Additional 6MWT Analyses
Patients performed two 6MWT evaluations on consecutive days at time points coinciding with a muscle biopsy procedure at baseline and Weeks 12, 24 and 48. All other evaluations were a single 6MWT. The pre-specified primary analysis included the maximum distance walked at those clinic visits where repeated tests were taken. Other analyses of the repeated 6MWT results assessed mean, minimum, and Day 1 (first measure) scores. Results from these additional 6MWT analyses confirm the robust treatment effect observed in the primary analysis.
Summary of 6MWT: Eteplirsen versus Placebo/Delayed-Treatment to Week 84*
* All 6MWT analyses are based on a Mixed Model Repeated Measures test.
Mr. Garabedian will present these data today at the
About the Phase IIb Eteplirsen Program (Studies 201 and 202)
Study 201 was a randomized, double-blind, placebo-controlled clinical study conducted at
At Week 25, all patients rolled over to Study 202, a long-term open-label extension study, and placebo-treated patients initiated eteplirsen treatment at 30 mg/kg (n=2) or 50 mg/kg (n=2).
The primary efficacy endpoint in Study 201 and Study 202 was the increase in novel dystrophin as assessed by muscle biopsy at Weeks 12 and 24 and at Week 48, respectively. The primary clinical endpoint was the 6MWT, a well-accepted measure of ambulation and clinical function in DMD. Long-term follow up in Study 202 continues to evaluate safety and clinical outcomes including the 6MWT.
About the 6-Minute Walk Test (6MWT)
The 6-minute walk test (6MWT) was developed as an integrated assessment of cardiac, respiratory, circulatory, and muscular capacity (
About the Statistical Methodology and the Modified Intent-to-Treat (mITT) Population
The Mixed Model Repeated Measures (MMRM) test was used for all statistical analyses of the 6MWT results. Baseline 6MWT scores and duration since DMD diagnosis were included as covariates.
The mITT population used in the 6MWT analyses consisted of 10 of the 12 enrolled patients, including 4 patients in the 50 mg/kg cohort, 2 patients in the 30 mg/kg cohort and 4 patients in the placebo/delayed-treatment cohort. Two patients in the 30 mg/kg cohort showed rapid disease progression upon enrollment and lost ambulation by Week 24, and thus were excluded.
All other data including safety, echocardiogram, pulmonary function tests, muscle strength measures and non-ambulatory functional tests were analyzed for all 12 patients.
About Duchenne Muscular Dystrophy
DMD is an X-linked rare degenerative neuromuscular disorder causing severe progressive muscle loss and premature death. One of the most common fatal genetic disorders, DMD affects approximately one in every 3,500 boys worldwide. A devastating and incurable muscle-wasting disease, DMD is associated with specific errors in the gene that codes for dystrophin, a protein that plays a key structural role in muscle fiber function. Progressive muscle weakness in the lower limbs spreads to the arms, neck and other areas. Eventually, increasing difficulty in breathing due to respiratory muscle dysfunction requires ventilation support, and cardiac dysfunction can lead to heart failure. The condition is universally fatal, and death usually occurs before the age of 30.
About Sarepta's Proprietary Exon-Skipping Platform Technology
Eteplirsen is Sarepta's lead drug candidate and is designed to address the underlying cause of DMD by enabling the production of a functional dystrophin protein. Data from clinical studies of eteplirsen in DMD patients have demonstrated a broadly favorable safety and tolerability profile and restoration of dystrophin protein expression.
Eteplirsen uses Sarepta's novel phosphorodiamidate morpholino oligomer (PMO)-based chemistry and proprietary exon-skipping technology to skip exon 51 of the dystrophin gene enabling the repair of specific genetic mutations that affect approximately 13 percent of the total DMD population. By skipping exon 51, eteplirsen may restore the gene's ability to make a shorter, but still functional, form of dystrophin from messenger RNA, or mRNA. Promoting the synthesis of a truncated dystrophin protein is intended to stabilize or significantly slow the disease process and prolong and improve the quality of life for patients with DMD.
Sarepta is also developing other PMO-based exon-skipping drug candidates intended to treat additional patients with DMD.
Forward-Looking Statements and Information
This press release contains forward-looking statements. These forward-looking statements generally can be identified by use of words such as "believes or belief," "anticipates," "plans," "expects," "will," "intends," "potential," "possible," "advance" and similar expressions. These forward-looking statements include statements about the development of eteplirsen and its efficacy, potency and utility as a potential treatment for DMD and the potential for the creation of novel dystrophin to lead to significant clinical benefit over a longer course of treatment.
Each forward-looking statement contained in this press release 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, among others: subsequent clinical trials may fail to demonstrate the safety and efficacy of eteplirsen or replicate results; treatment of patients with DMD using eteplirsen over a longer duration may not lead to significant clinical benefit; any of Sarepta's drug candidates, including eteplirsen, may fail in development, may not receive required regulatory approvals (including Subpart H accelerated approval), or may not become commercially viable due to delays or other reasons; and those identified under the heading "Risk Factors" in Sarepta's Annual Report on Form 10-K for the full year ended
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