Key Developments For AVI BioPharma, Inc.
AVI BioPharma, Inc. (AVII.O) (Consolidated Issue listed on NASDAQ Global Market)
AVI BioPharma, Inc. Updated Safety Data From Ongoing Systemic Trial Of AVI-4658
AVI BioPharma, Inc. announced an update on preliminary safety data from its ongoing systemic Phase 1b/2 clinical trial of exon skipping AVI-4658 in patients with Duchenne muscular dystrophy (DMD). The most recent data from the ongoing Phase 1b/2 trial at two MDEX sites in the UK demonstrate that AVI-4658 was well tolerated by DMD patients in a dose escalation study that is now up to the fifth cohort (10 mg/kg). Results from the 12 week dosing periods of the first four completed cohorts (0.5 mg/kg, 1.0 mg/kg, 2.0 mg/kg and 4.0 mg/kg) have been reviewed with data from the ongoing cohort 5 (10 mg/kg) and have demonstrated the drug to be well tolerated. There have been no safety issues identified, although one Serious Adverse Event was reported due to an anaesthetic-induced post-treatment biopsy procedure at 14 weeks, 2 weeks after last dose, causing nausea and vomiting. The maximum cumulative dose administered to date is 2797 mg and the maximum single dose is 300 mg with no signs of intolerance, in either case. Blood tests, including measures of coagulation, have remained satisfactory, with the elevated levels of muscle enzyme, creatine kinase tending to fall in most boys during treatment. Lung function, vital signs and examinations have also remained stable. In addition, no significant side effects from the treatment have been reported for any of the 16 boys treated to date.
AVI BioPharma, Inc. To Present Safety Update From Ongoing Systemic Trial Of AVI-4658
AVI BioPharma, Inc. announced that it will present updated preliminary safety data from its ongoing systemic Phase 1b/2 clinical trial of AVI-4658 in patients with Duchenne muscular dystrophy (DMD) at the 7th Annual Action Duchenne Conference taking place Oct. 23-24 in London, UK. Previously announced results from the ongoing Phase 1b/2 systemic trial have demonstrated that AVI-4658 has been well tolerated in patients with DMD in the first two completed cohorts (0.5 mg/kg and 1.0 mg/kg) and two ongoing cohorts (2.0 mg/kg and 4.0 mg/kg). There have been no drug-related safety issues identified. Data to be presented at the conference will include updated safety information from the four patients being dosed in the penultimate dose cohort (10 mg/kg). In each cohort, including the final cohort of 20 mg/kg, data for the clinical effects of the treatment will be collected for 26 weeks from first dose. The open label dose-finding clinical trial is evaluating the systemic delivery of AVI-4658 once per week for 12 weeks by slow intra-venous infusion. Although the study is primarily a safety trial, it includes measures of drug efficacy and pharmacokinetics and is being conducted in London, UK at the UCL Institute of Child Health / Great Ormond Street Hospital NHS Trust facilities and at the Royal Victoria Infirmary, Newcastle-Upon-Tyne, UK, which is the coordinating center for the European Treat Neuromuscular Diseases (Treat-NMD) initiative.
AVI BioPharma, Inc. Announces Exon Skipping Drug Prevents Muscle Wasting and Maintains Muscle Function in Severely Affected, Dystrophin Deficient
AVI BioPharma, Inc. announced that an exon skipping PPMO has demonstrated dramatic effects in the prevention and treatment of severely affected, dystrophin and utrophin-deficient mice, preventing severe deterioration of the treated animals and extending their lifespan. These findings support the promise of this therapeutic approach for the treatment of Duchenne muscular dystrophy (DMD). Studies and research have shown that the ability to skip certain exons in dystrophin pre-mRNA could circumvent these dystrophin gene errors and provide a potential treatment for DMD patients. The paper Prevention of Dystrophic Pathology in Severely Affected Dystrophin/Utrophin-deficient Mice by Morpholino-oligomer-mediated Exon-skipping details the successful exon skipping and treatment of utrophin/dystrophin double knockout (dKO) mice with a cell-penetrating peptide-conjugated phosphorodiamidate morpholino oligomers (PPMO) targeting exon 23 in dystrophin pre-mRNA. Videos show visual evidence of pronounced curving of the spine and dramatically reduced mobility as a result of deficiency of both dystrophin and utrophin proteins (dKO Mouse No Treatment/Supplementary Video S1). Treatment of affected mice from 10 days of age for six weeks with the mouse-specific PPMO at a dosage of 25 mg/kg/week resulted in a nearly complete skipping of exon 23 in all of the muscles examined except the heart.
AVI BioPharma, Inc. Announces Exon Skipping Therapy Shows Promise in Prevention or Delay of Heart Disease Associated With Duchenne Muscular Dystrophy
AVI BioPharma, Inc. announced the publication of research demonstrating the ability of a peptide-conjugated phosphorodiamidate morpholino oligomer (PPMO) therapy to prevent the onset of cardiomyopathy in a mouse model of Duchenne muscular dystrophy (DMD). The paper Long-Term Improvement in mdx Cardiomyopathy after Therapy with Peptide-conjugated Morpholino Oligomers was authored by researchers at the University of North Carolina at Chapel Hill and AVI and published online, in advance of print, in the journal Cardiovascular Research. In the study, mice lacking dystrophin in their heart and skeletal muscles were given a PPMO that delivered a splice-switching oligonucleotide-mediated exon skipping therapy to restore dystrophin in mdx mice before the development of detectable cardiomyopathy. Results demonstrated that the PPMO successfully restored cardiac dystrophin expression, preserved cardiac sarcolemma integrity, and prevented the development of cardiac pathology that develops in such mice over time. Echocardiography and Doppler analysis demonstrated that 5-6 week treatment prevented cardiac hypertrophy and diastolic dysfunction, characteristic of DMD patients early in the disease process. PPMO therapy provided a durable cardiac improvement up to 7 months after the initiation of treatment.
AVI BioPharma, Inc. Receives Expanded Contract From U.S. Department Of Defense To Develop Drug Candidate For Treatment Of Junin Virus Infection
AVI BioPharma, Inc. announced that it has received expanded contract funding of approximately $11.5 million from the Defense Threat Reduction Agency's (DTRA) Transformational Medical Technologies Initiative (TMTI) to support development of the Investigational New Drug (IND) data package for its candidate drug, AVI-7012, to treat Junin virus infection. To date, the United States Department of Defense (DoD) has contracted with AVI for work potentially worth up to $45 million for the development of AVI's RNA-based drug candidates to treat Ebola, Marburg and Junin virus infections (AVI-6002, AVI-6003 and AVI-7012, respectively). AVI has received a 'safe to proceed' allowance from the United States Food and Drug Administration (FDA) for IND applications for clinical safety trials of its two lead products to treat Ebola and Marburg virus infections. These INDs represent the first TMTI supported drug candidates targeting bioterrorism agents to receive FDA IND allowance. AVI plans to conduct the animal efficacy trials for potential approval of its drugs under the Animal Rule as part of its continued collaboration with U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID).
