Bothell, WA-based AVI Biopharma (NASDAQ: AVII) is trying to develop the first treatment to correct an underlying molecular abnormality in boys with Duchenne Muscular Dystrophy, and after taking an early peek at a small clinical trial, the drug appears to be doing what it’s supposed to do in at least one patient.
The preliminary results were from an initial phase trial from the first 9 out of 18 boys who completed dosing at a single site in the U.K., with once-weekly intravenous infusions of the treatment, AVI-4658, over a period of 12 weeks. The trial initially enrolled patients to receive extremely low doses of the drug, and when it appeared safe, enrolled more patients in higher dose groups. AVI Biopharma and its academic collaborators didn’t see evidence of an effect at the lowest doses, but they did among three boys who got mid-range doses of 2 and 4 milligrams per kilogram, which showed the drug corrected the molecular abnormality it is designed to fix. One of the boys was able to produce five-fold higher amounts of a protein called dystrophin, a key structural component of muscle that is lacking in patients with Duchenne Muscular Dystrophy, based on a biopsy of bicep muscle.
AVI doesn’t have data in hand that connects the dots to show that the molecular changes induced by the drug will actually reverse the disability associated with muscular dystrophy. Still, “these results suggest that we are on the right path towards developing a drug that could play a role in the treatment of Duchenne Muscular Dystrophy,” said Francesco Muntoni, Professor of Pediatric Neurology and Head of the Dubowitz Neuromuscular Centre at the University College London, and the trial’s lead investigator.
“We weren’t really expecting to see dystrophin expressed, based on the animal models, until we got to higher doses of 4 and 10 milligrams per kilogram,” says AVI chief medical officer Steve Shrewsbury. “It’s a nice way for us to round out the year and start the new year.”
Biotech companies haven’t traditionally shown much interest in muscular dystrophy, although that’s changing as researchers gather understanding of the genetic underpinnings of the disease. The AVI treatment is part of an emerging class of compounds known as antisense oligonucleotides.
What’s special about the AVI treatment is that it’s designed to silence a specific stretch of RNA and, by doing so, enable the body to produce dystrophin. The drug recently earned notice in The Lancet when it showed an ability to restore some production of dystrophin proteins in an previous early-stage clinical trial—although it didn’t fully restore the dystrophin. That earlier trial also was very limited in that it involved a direct injection into a foot muscle, and the AVI drug wasn’t yet formulated into a more practical intravenous infusion that circulates throughout the body, as was used in the study reported today.
If AVI can show in subsequent trials that its drug is safe, and can be delivered throughout the body, it would be a big step forward even if it’s modestly effective, University of Washington researcher Jeff Chamberlain told me back in September. About one in every 3,500 boys born worldwide have Duchenne Muscular Dystrophy.
AVI said its treatment appeared to be well-tolerated in the current study, and boys in the study reported the usual headache, muscle ache, and upper respiratory infections often seen in pediatric studies. One patient dropped out of the trial with heart damage (cardiomyopathy), although researchers didn’t consider that drug-related. Two more serious adverse events were reported among patients during the 14-week follow-up period after they quit taking the drug, and those also weren’t considered drug-related, AVI said.
Much more data is still to come from this trial in the U.K. Another eight patients are receiving treatment at higher doses of 10 and 20 milligrams per kilogram for 12 weeks, and if the trend continues from what researchers saw in the mid-range doses, then those boys could start producing even more dystrophin. AVI says it has completed the required studies in mice and monkeys that it needs to open a clinical trial in the U.S.
Once all of the follow-up data is in from this trial in the U.K., AVI is hopeful that it will be able to draw a connection between increased production of dystrophin and an improvement in patients’ muscular dystrophy symptoms. The full data will be published in a scientific journal, says CEO Les Hudson.
Shares of AVI climbed 6 percent at the opening bell today to $1.59.