Spinal Muscular Atrophy, or SMA, is a deadly inherited disease. It affects about 1 of 10,000 babies, but it tends to be fatal—it’s the number one genetic cause of death for infants, and most of them die by age 3.
There is no approved treatment for SMA, and as a result, it’s become a big target for several drugmakers, among them Carlsbad, CA-based Isis Pharmaceuticals (NASDAQ: ISIS). But others are trying, too, like a Dallas biotech named AveXis, which last week raised $10 million in venture cash to fund clinical trials for its own experimental therapy.
SMA is caused by a mutation in the motor neuron gene 1, which results in an attack on the central nervous system, taking away the ability to walk, eat, or breathe. In healthy people, the neuron produces a protein that is critical to the function of nerves that control muscles. Without it, these nerve cells die, leading to debilitating, and fatal, muscle weakness.
AveXis is trying to treat the disease with gene therapy, a process by which healthy genes are transported, typically by a virus, into cells to treat disease. AveXis’s gene therapy candidate, ChariSMA, for instance, is supposed to provide patients with a functional SMN gene. The therapy is delivered via a specific type of adeno-associated virus, or AAV, which CEO and co-founder John Carbona says can cross the blood-brain barrier.
“They are born with X number of motor neurons and every day they start to lose them,” he says of SMA-afflicted infants. “We use their own genes to stop the destruction, maintain the existing [genes], and prevent further loss.”
AveXis is focusing on treating SMA 1, which occurs in babies from birth to six months of age. In May 2014, the biotech dosed the first patient in it’s first trial, a now 1-year-old who is still alive, Carbona says. While a single example, that’s significant because about half of newborns diagnosed with SMA typically die at 10 months of age. AveXis has enrolled four patients, and evaluating the safety and efficacy of the therapy.
Of the four children are in the trial, one is getting a low dose, two are receiving twice that dose, the fourth is getting the highest dose of the drug. This highest dose “completely rescued the mice … that were supposed to die in two weeks” in animal studies, Carbona says.
The funds from the group of investors, led by Deerfield Management in New York and Roche Venture Fund (the venture arm of Roche), will be used for at least one additional trial AveXis is running with the help of Nationwide Children’s Hospital in Columbus, OH. Children will get a mid-range dose in the trial. In total, Carbona says the company hopes to have dosed 18 total children both intravenously and intrathecally in both trials.
Good results will help AveXis edge into a competitive space with some large, well-financed players. The company, which was founded in 2013, is a relative newcomer to the SMA field.
In 2012, Isis announced it was partnering with Biogen Idec (NASDAQ: BIIB) on an experimental antisense drug for SMA. The drug candidate is delivered through an injection into the spine, and earlier this month, Isis reported that it had received a $7 million payment from Biogen to advance an ongoing open-label extension study, which is evaluating its drug candidate in a phase III trial with 110 children.
Roche and PTC Therapeutics (NASDAQ: PTCT) are also developing a treatment via a partnership began in 2011. They’re trying to use a process called “alternative splicing” to generate drugs that would prompt a backup SMN gene to produce more of the vital protein.
In November, the two companies announced that they started a Phase 1b/2a study in both adult and pediatric patients with the help of the SMA Foundation. They aim to enroll 48 patients in the trial.
Founded two years ago,AveXis was formed out of another Dallas venture, the BioLife Cell Bank, which stores stem and fat cells. Carbona, who had been CEO of the cell bank, says he saw the possibility of gene therapy for SMA treatment and left to form AveXis. The company has licensed its technology from Ohio State University and Brian Kaspar, a principal investigator at The Research Institute at Nationwide Children’s Hospital and an associate professor at the university’s medical school.
Last year, AveXis entered into an agreement with Washington, D.C.-based Regenx to use one of the company’s viral vectors to deliver ChariSMA (several other gene therapy upstarts, like AAVLife, Audentes Therapeutics, and Dimension Therapeutics, are similarly using RegenX vectors). The company has obtained orphan status for its drug candidate.
I spoke to Carbona right after his red-eye flight to Dallas from San Francisco, where he had attended the J.P. Morgan Healthcare Conference, the biotech industry’s biggest annual gathering. In addition to securing the new funds, he says the company is working on doing pre-clinical and then clinical trials in Europe. AveXis is aims to have drugs on the market by 2018, he added.
There’s a long road ahead, but AveXis’s progress is sure to be closely watched by its rivals.
“We were one of the belles of the ball,” he says, referring to the J.P. Morgan conference. “I suspect that big pharma is paying larger attention to our results.”