CAMBRIDGE, MA -- (Marketwired) -- 04/05/13 -- Sarepta Therapeutics, Inc. (NASDAQ: SRPT), a developer of innovative RNA-based therapeutics, today announced updated data from Study 202, a Phase IIb open-label extension study of eteplirsen in patients with Duchenne muscular dystrophy (DMD). Results at 74 weeks showed a continued stabilization of walking ability in eteplirsen-treated patients evaluable on the 6-minute walk test (6MWT). As previously reported, Study 202 met its primary endpoint of increased novel dystrophin as assessed by muscle biopsy at week 48 and is now in the long-term extension phase in which patients continue to be followed for safety and clinical outcomes. Eteplirsen is Sarepta's lead exon-skipping compound in development for the treatment of patients with DMD who have a genotype amenable to skipping of exon 51.

After 74 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 65.2 meters (p ≤ 0.004) when compared to the placebo/delayed-treatment cohort (n=4). The eteplirsen-treated patients in the mITT population demonstrated less than a 5 percent decline (13.4 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 74, the period in which meaningful levels of dystrophin were likely produced, with a less than 10 meter decline over this timeframe.

"We are encouraged to see a continued stabilization of walking ability in patients treated with eteplirsen for nearly one and a half years," said Chris Garabedian, president and chief executive officer of Sarepta Therapeutics. "These data are particularly compelling when viewed in the context of published natural history studies, which showed substantial declines on the 6-minute walk test over this timeframe in a similar ambulatory DMD population. These results continue to support the potential of eteplirsen to be a major advance in the treatment of DMD in altering the course of this progressive and irreversible disease."

Through 74 weeks, eteplirsen was well tolerated and there were no clinically significant treatment-related adverse events, serious adverse events, hospitalizations or discontinuations. As previously reported at 62 weeks, one patient had a transient elevation of urine protein on a laboratory urine dipstick test, which resolved and resulted in no clinical symptoms. The patient continued treatment without interruption and remained free of proteinuria through week 74.

Across both the eteplirsen (mITT) and placebo/delayed-treatment cohorts, there is evidence of continued stabilization on clinical laboratory tests, echocardiogram, pulmonary function tests and 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 (mITT) versus Placebo/Delayed-Treatment to Week 74*

*All analyses are based on a Mixed Model Repeated Measures test.

Jerry R. Mendell, M.D., Director of the Centers for Gene Therapy and Muscular Dystrophy atNationwide Children's Hospital and principal investigator of the Phase IIb study, will present these data in an oral presentation at the Muscular Dystrophy Association Scientific Conference on Tuesday, April 23 at 4:05 p.m. EDT in Washington, D.C. Dr. Mendell's presentation will be posted on the Sarepta website in the "Events & Presentations" section after the session is completed.

Oct 03, 2012 (Marketwire via COMTEX) --Sarepta Therapeutics (NASDAQ: SRPT), a developer of innovative RNA-based therapeutics, today announced that treatment with its lead exon-skipping compound, eteplirsen, met the primary efficacy endpoint, increase in novel dystrophin, and achieved a significant clinical benefit on the primary clinical outcome, the 6-minute walk test (6MWT) over the placebo/delayed treatment cohort in a Phase IIb extension trial in Duchenne muscular dystrophy (DMD) patients. 

Eteplirsen administered once weekly at either 30 mg/kg or 50 mg/kg for 48 weeks (n=8) resulted in a statistically significant increase (p≤0.001) in dystrophin-positive fibers to 47.0% of normal. The placebo/delayed treatment cohort, which had received 24 weeks of eteplirsen at either 30 mg/kg or 50 mg/kg following 24 weeks of placebo (n=4), also showed a statistically significant increase in dystrophin-positive fibers to 38.3% of normal (p≤0.009).

"These data represent a significant milestone and a defining moment of progress and hope for patients with DMD and their families, as well as for those of us in the scientific community who have been pursuing potential treatments for this devastating and deadly disease for decades," said Jerry Mendell, M.D., Director of the Centers for Gene Therapy and Muscular Dystrophy at Nationwide Children's Hospital and principal investigator of the Phase IIb study. Dr. Mendell added, "By addressing the underlying cause of DMD, eteplirsen has demonstrated unparalleled effects on enabling dystrophin production and slowing the progression of the disease as measured by the 6-minute walk test, with no treatment associated adverse events. While eteplirsen is targeted to DMD patients with a specific genetic mutation, I think the implications for all DMD patients with related genetic mutations are clearly evident." 

Eteplirsen administered once weekly at 50 mg/kg over 48 weeks resulted in an 89.4 meter benefit compared to patients who received placebo for 24 weeks followed by 24 weeks of treatment with eteplirsen in the open-label extension. In the predefined prospective analysis of the study's intent-to-treat (ITT) population on the primary clinical outcome measure, the change in 6MWT distance from baseline, eteplirsen-treated patients who received 50 mg/kg of the drug weekly (n=4) demonstrated an increase of 21.0 meters in distance walked from baseline (mean=396.0 meters), while patients who received placebo/delayed-eteplirsen treatment (n=4) showed a decline of 68.4 meters from baseline (mean=394.5 meters), for a statistically significant treatment benefit of 89.4 meters over 48 weeks (p=0.016, using ANCOVA for ranked data). There was no statistically significant difference between the cohort of patients who received 30 mg/kg weekly of eteplirsen and the placebo/delayed treatment cohort.

"We are extremely excited about these data, as they demonstrate that longer-term treatment with eteplirsen is translating to continued and unprecedented increases in both dystrophin production and clinical benefit across various subgroups of DMD patients involved in this study," said Chris Garabedian, President and CEO of Sarepta Therapeutics. "On a broader scale, these results signify the promise and tremendous potential of our RNA-based technology to impact and modulate disease at the genetic level, which may lead to first-ever opportunities to target serious and life-threatening rare conditions at the origin of disease." 

The safety profile of eteplirsen was evaluated across all subjects through 48 weeks and there were no treatment-related adverse events, no serious adverse events, and no discontinuations. Furthermore, no clinically significant treatment-related changes were detected on any safety laboratory parameters, including several biomarkers for renal function.

Summary of Dystrophin: Eteplirsen-Treated Patients in All Dose Groups through Week 48*

* Values based on Immunofluorescence using anti-dystrophin antibody MANDYS106

Modified Intent-to-Treat (mITT)

The 6MWT results were further analyzed using the mITT population which excluded two patients who were randomized to the 30 mg/kg weekly eteplirsen cohort who showed signs of rapid disease progression within weeks after enrollment and were unable to perform measures of ambulation beyond 24 weeks. This mITT population consisted of 10 patients (4 eteplirsen-treated patients receiving 50 mg/kg weekly, 2 eteplirsen-treated patients receiving 30 mg/kg weekly, and 4 placebo/delayed-treatment patients).

Summary of 6MWT: Eteplirsen versus Placebo/Delayed-Treatment to Week 48*

*Note: Analysis based on Mixed Model Repeated Measures test

Summary of Additional Sub-Group Analyses at Week 48*

 * Note: Analysis based on Mixed Model Repeated Measures test

An abstract describing the results from this Phase IIb extension study has been accepted as part of the World Muscle Society (WMS) Congress's Late-Breaking Science program in Perth, Australia during October 9 to October 13, 2012. Principal investigator, Jerry R. Mendell, M.D. of Nationwide Children's Hospital, will present the data via an oral presentation of the abstract titled, "Results at 48 Weeks of a Phase IIb Extension Study of the Exon-Skipping Drug Eteplirsen in Patients with Duchenne muscular dystrophy (DMD)." Dr. Mendell will present on October 13 at 4:00 p.m. WST UTC +8 hours/4:00 a.m. EDT. Dr. Mendell's presentation will be posted on the Sarepta website in the "Events & Presentations" section after the session is completed. In addition, Sarepta is sponsoring an educational symposium at WMS chaired by Professor Steve Wilton, PhD, Head of the Molecular Genetic Therapy Group and Director of Translational Research and Development, Australian Neuromuscular Research Institute at the University of Western Australia. Professor Wilton is a long-time collaborator of Sarepta's whose groundbreaking research has extended the use of antisense oligomers to DMD.

About Study 201 and Study 202 (Phase IIb Eteplirsen Study)

Study 4658-US-201 was conducted at Nationwide Children's Hospital in Columbus, Ohio. Twelve boys meeting the inclusion criteria being between 7 and 13 years of age with appropriate deletions of the dystrophin gene that confirm eligibility for treatment with an exon-51 skipping drug, received double-blind IV infusions of placebo (n=4), 30 mg/kg of eteplirsen (n=4), or 50 mg/kg of eteplirsen once weekly for 24 weeks (n=4). Muscle biopsies for evaluation of dystrophin were obtained at baseline for all subjects, and after 12 weeks for patients in the 50 mg/kg cohort and after 24 weeks for patients in the 30 mg/kg cohort. Two placebo patients were randomized to the 30 mg/kg cohort and two placebo patients were randomized to the 50 mg/kg cohort. This study design allowed Sarepta to investigate the relationship of dose and duration of eteplirsen treatment on the production of dystrophin over the course of the 24-week study.

Study 4658-US-202 is the extension study to 201 and continues to assess the long-term safety and efficacy of open-label eteplirsen. The four placebo patients were rolled over to open-label eteplirsen at week 24, with six patients on 30 mgs/kg, and six patients on 50 mgs/kg. Third biopsies occurred at 48 weeks in the original study 201 treated patients, and at 24 weeks, the same time point, in the original placebo patients. 6MWT was performed at 32 weeks, 36 weeks, 48 weeks and will continue to be performed every 12 weeks going forward.

BOTHELL, WA, Apr 02, 2012 (MARKETWIRE via COMTEX) --AVI BioPharma, Inc. (NASDAQ: AVII), a developer of RNA-based therapeutics, today announced that treatment with eteplirsen met the primary efficacy endpoint in a randomized, double-blind, placebo-controlled Phase IIb study in boys with Duchenne muscular dystrophy (DMD). Eteplirsen administered once weekly at 30mg/kg over 24 weeks resulted in a statistically significant (p ≤ 0.002) increase in novel dystrophin (22.5% dystrophin-positive fibers as a percentage of normal) compared to no increase in the placebo group.

"This study represents a major advance in the field of DMD research as the results indicate that eteplirsen is producing consistent levels of dystrophin, which is the essential protein that these patients need," said Jerry Mendell, M.D., Director of the Centers for Gene Therapy and Muscular Dystrophy at Nationwide Children's Hospital and principal investigator of the Phase IIb study. Dr. Mendell added, "We anticipate that these levels of dystrophin could lead to significant clinical benefit if maintained over a longer course of treatment."

In the study, a shorter duration of eteplirsen treatment, 12 weeks, did not show a significant increase in novel dystrophin (0.79% dystrophin-positive fibers as a percentage of normal; p-value NS), despite administration of the drug at a higher dose (50mg/kg once weekly). This finding suggests that a longer duration of dosing is required before meaningful levels of dystrophin are produced. There were no significant improvements in clinical outcomes in the treated groups compared to placebo. Performance on the 6-minute walk test and other outcome measures were generally stable across most of the patients, including the placebo patients, suggesting that a longer period of observation will be required to demonstrate clinical effects of eteplirsen versus a placebo control.

Eteplirsen was well tolerated at both dose levels through 24 weeks of treatment. There were no treatment-related adverse events, no serious adverse events, and no treatment discontinuations related to eteplirsen. Furthermore, no treatment related changes were detected on any safety laboratory parameters, including several biomarkers for renal function.

"We are very encouraged by the results of this first placebo-controlled study investigating exon-skipping technology in DMD," said Chris Garabedian, President and CEO of AVI BioPharma. "Eteplirsen represents the first drug candidate for DMD to demonstrate the production of novel dystrophin in a robust and consistent manner and these study results support advancing eteplirsen into a pivotal study."