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27 MAR 2013
The clock is ticking for Sarepta Therapeutics , a multitude of biotech investors and the boys who suffer from Duchenne muscular dystrophy.
Armed with promising Phase IIb data from a small study of eteplirsen involving only 12 patients with the lethal disease, Sarepta CEO Chris Garabedian is completing one of the most closely-watched high wire acts in the industry. At a time most companies would be focused solely on organizing a pivotal late-stage study, there’s intense speculation that the biotech will shoot for an accelerated approval with the data in hand. And it all comes down to their sit-down with the FDA to review mid-stage data.
Eteplirsen, also called AVI-4658, is an experimental drug, currently in clinical trials. It is designed for treatment of some mutations which cause Duchenne muscular dystrophy (DMD), a genetic degenerative muscle disease. Eteplirsen is a product of Sarepta Therapeutics Inc.
The drug is a Morpholino antisense oligomer which triggers excision of exon 51 during pre-mRNA splicing of the dystrophin RNA transcript. Skipping exon 51 changes the downstream reading frame of dystrophin; giving eteplirsen to a healthy person would result in production of dystrophin mRNA which would not code for functional dystrophin protein but, for DMD patients with particular frameshifting mutations, giving eteplirsen can restore the reading frame of the dystrophin mRNA and result in production of functional (though internally-truncated) dystrophin. Eteplirsen is given by intravenous infusion for systemic treatment of DMD.
Several clinical trials have been conducted to test eteplirsen, one in the UK involving local injection to the foot, one in the UK involving systemic injection at low doses and one in the USA at higher systemic doses that progressed to a rollover extension study.
- “Exon Skipping Quantification by qRT-PCR in Duchenne Muscular Dystrophy Patients Treated with the Antisense Oligomer Eteplirsen”. Hum Gene Ther Methods. 17 Oct 2012.
- “Morpholinos and Their Peptide Conjugates: Therapeutic Promise and Challenge for Duchenne Muscular Dystrophy.”. Biochim Biophys Acta. 1798 (12): 2296–303. 17 Feb 2010.
- Gary Roper/Manager Clinical Research Governance Organisation, Imperial College London. “Safety and Efficacy Study of Antisense Oligonucleotides in Duchenne Muscular Dystrophy”. ClinicalTrials.gov. US Government, NIH. Retrieved 30 October 2012.
- Lancet Neurol. 8 (10): 918–28. 25 Aug 2009.
- Professor Francesco Muntoni, University College of London Institute of Child Health. “Dose-Ranging Study of AVI-4658 to Induce Dystrophin Expression in Selected Duchenne Muscular Dystrophy (DMD) Patients”. ClinicalTrials.gov. US Government, NIH. Retrieved 30 October 2012.
- “Exon skipping and dystrophin restoration in patients with Duchenne muscular dystrophy after systemic phosphorodiamidate morpholino oligomer treatment: an open-label, phase 2, dose-escalation study.”. Lancet. 378 (9791): 595–605. 23 Jul 2011.
- Sarepta Therapeutics. “Efficacy Study of AVI-4658 to Induce Dystrophin Expression in Selected Duchenne Muscular Dystrophy Patients”. ClinicalTrials.gov. US Government, NIH. Retrieved 30 October 2012.
- Sarepta Therapeutics. “Efficacy, Safety, and Tolerability Rollover Study of Eteplirsen in Subjects With Duchenne Muscular Dystrophy”. ClinicalTrials.gov. US Government, NIH. Retrieved 30 October 2012.