AVI BioPharma Reports Initial Efficacy Data On AVI-4658

AVI BioPharma has presented initial efficacy data from the ongoing phase 1b/2 clinical trial 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.

The company claims that analysis of the post treatment biopsies found that patients in the 2 and 4mg/kg drug-treatment cohorts (3 of 3 in total) showed correctly spliced mRNA for dystrophin. One of these patients, in the 2mg/kg cohort, showed robust expression of dystrophin protein by western blot and immunofluorescent analysis.

No RNA or protein expression signal was detected in patients from the 0.5mg/kg or 1.0mg/kg cohorts after completing treatment. Restoration of functional dystrophin expression is considered critical for successful treatment of DMD.

Treatment with AVI-4658 in the three patients in the 2.0 and 4.0mg/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.

Francesco Muntoni, professor of Pediatric Neurology and head of the Dubowitz Neuromuscular Centre and the lead investigator of trial, said: “I am encouraged by the evidence of accurate skipping of exon 51 in three treated patients. These results suggest that we are on the right path towards developing a drug that could play a role in the treatment of DMD.

“The fact that one patient at the 2mg/kg dose showed significant expression of dystrophin protein leads us to expect greater levels of dystrophin expression following treatment with the higher doses of 10.0 mg/kg and 20.0 mg/kg of AVI-4658, which are currently underway in the trial.”