eteplirsen

(redirected from AVI-4658)

eteplirsen

A proprietary agent in clinical trials for managing Duchenne muscular dystrophy, a condition characterised by defective dystrophin—a key cytoplasmic protein that links muscle fibre cytoskeleton to extracellular matrix through the cell membrane.

Mechanism
Eteplirsen is a splice-switching oligomer that skips exon 51 of the dystrophin gene-DMD, resulting in the production of a shorter, but still functional, dystrophin.
References in periodicals archive ?
The "antisense" drug, known as AVI-4658, is a synthetic form of the genetic chemical RNA.
In this clinical trial of 19 patients, study participants aged five to 15 at Great Ormond Street Hospital and the Royal Victoria Infirmary, Newcastle, were given weekly doses of the drug, AVI-4658. The drug had already been tested for safety and efficacy by the MDEX Consortium and AVI Biopharma in an earlier phase of the study.
Top-line biopsy data showed the generation of muscle fibers with the protein dystrophin of more than 50% of normal in a patient suffering from Duchenne muscle dystrophy (DMD), after being given the drug, AVI-4658. Lack of the protein causes the condition, which weakens the muscle and eventually leads to paralysis.
"All eight patients in the 10 and 20 mg/kg cohorts treated with AVI-4658 showed generation of new dystrophin-positive muscle fibers," the company said in a statement.
The company is currently conducting a dose-finding clinical trial evaluating the systemic delivery of its lead drug candidate, AVI-4658. This ongoing Phase 1b/2 open label clinical trial is assessing the safety, tolerability, pharmacokinetics and exploratory efficacy of AVI-4658 in ambulatory DMD boys aged between five and 15 who have an error in the gene coding for dystrophin that could be treated by skipping exon 51.
AVI-4658, another drug being developed by AVI for DMD, received European orphan drug designation in 2008, and also potentially may receive up to 10 years of marketing exclusivity if approved in the EU.
23 December 2009 - US biopharmaceutical company AVI BioPharma Inc (NASDAQ: AVII) reported yesterday initial efficacy data from the ongoing Phase Ib/II study of AVI-4658 for the systemic treatment of patients with Duchenne muscular dystrophy (DMD).
Patients in the first four (of six) cohorts completing 12 weeks of treatment with different doses of AVI-4658 (0.5, 1.0, 2.0 or 4.0 mg/kg) have had their muscles biopsied.
Treatment with AVI-4658 in the three patients in the 2.0 and 4.0 mg/kg cohorts led to accurate skipping of exon 51, which is believed to be necessary to restore the mRNA reading frame for functional dystrophin expression in patients with this class of mutations.
Study 28 is a Phase Ib/II open label, dose-ranging clinical trial assessing the safety, tolerability, pharmacokinetics and exploratory efficacy of AVI-4658 in ambulatory DMD boys between the ages of 5 and 15 years of age who have an error in the gene coding for dystrophin that could be treated by skipping exon 51.
Data from patients dosed to date demonstrate that AVI-4658 continues to be generally very well tolerated.