Voyager Therapeutics this afternoon is providing very early evidence that an experimental gene therapy it’s been developing might have a chance to help patients with Parkinson’s disease for whom standard treatment is no longer working well.
Cambridge, MA-based Voyager (NASDAQ: [[ticker:VYGR]]) is disclosing interim data from a small, open-label, Phase 1 trial among volunteers with a waning response to levodopa, a decades-old drug that most Parkinson’s patients take to deal with their symptoms. Voyager has treated 10 patients so far: five apiece on a low or high dose of its gene therapy, VY-AADC01. Today’s data includes results from all 10 patients after six months of follow-up, and eight patients (five on a low dose and three on a high dose) after a year of follow-up.
These are very small numbers in a trial that doesn’t include a placebo arm. Voyager needs to treat many more patients, over a longer period of time, to really prove the worth of VY-AADC01. Voyager’s biggest test—a placebo-controlled study that should begin by the end of 2017—will be much more telling than the results of this trial.
But Voyager officials say the data so far show that the gene therapy appears to be helping this small group of patients respond better to levodopa than they were before treatment, and that that benefit is translating to improvements in motor function. These patients have also been able to cut down the amount of levodopa they’re taking since undergoing treatment with VY-AADC01.
The high dose appears to work better than the low dose, and the benefits have come without any significant side effects from the gene therapy agent. (Earlier this year, Voyager reported one significant health problem in the study, a blood clot in the lungs, that resulted from the brain surgery required to administer VY-AADC01; VP of clinical development Bernard Ravina says the company has since tweaked the procedure and hasn’t seen any further problems arise.)
“We’re seeing all the clinical stuff stack up in the right direction,” Ravina says.
According to the National Parkinson Foundation, about 1 million Americans and 4 to 6 million people worldwide suffer from the disease, which causes motor symptoms like tremors, loss of movement, and stiff limbs, and cognitive problems like confusion and memory loss. Those numbers are expected to increase substantially in the next few decades as the population ages. As the disease progresses, patients can have trouble walking, speaking, or functioning without the help of a caregiver.
Voyager estimates that about 10 percent of Parkinson’s patients, some 100,000 in the U.S., are “refractory” to treatment with levodopa—the standard of care for Parkinson’s since the 1960s—or other drugs. Those are the folks who would be eligible for a treatment like VY-AADC01, according to Ravina.
Much remains unknown about the disease’s underlying biology, but one thing that’s clear is that its hallmark motor symptoms arise from the death of neurons in the brain that produce the neurotransmitter dopamine. There are no drugs that actually slow or reverse the course of the disease, but levodopa has made a monumental difference in the treatment of the disorder since its discovery (which earned a Nobel prize for Swedish scientist Arvid Carlsson in 2000). It helps nerve cells make dopamine, which in turn helps patients manage symptoms and function normally for a longer period of time.
Patients who start taking levodopa go through a “honeymoon” phase where the treatment is so effective they don’t have any symptoms. But over time patients’ responses start to levodopa start fluctuating. There are fewer hours per day of “on” time, when the drug is working, and more “off” time. To compensate, patients increase their levodopa doses, but that can cause dyskinesia, or uncontrollable, spastic movements.
There are a few drugs in development meant to combat the fluctuating response problem—inhalable forms of levodopa being advanced by Acorda Therapeutics (NASDAQ: [[ticker:ACOR]]) and Sunovion Pharmaceuticals are supposed to be rescue therapies for “off” episodes. Other experimental drugs in development aim to slow or reverse the course of the disease. Voyager has taken a different approach. It’s using gene therapy—a method of shuttling genetic instructions into the body to fix a disease-related malfunction—to, Ravina says, “turn back the clock” and enable patients to respond to levodopa the way they may have earlier in their disease.
As Parkinson’s progresses, patients have lower levels of the enzyme—aromatic L-amino acid decarboxylase (AADC)—that converts levodopa to dopamine, which is why they stop responding to the drug. Voyager puts a gene that produces AADC into an engineered virus and injects it directly into the putamen, a part of the brain associated with motor function. The surgery takes about 8 to 10 hours, Ravina says. Patients leave the hospital a day or two later.
Gene therapy has been tried for this purpose in Parkinson’s before—initial research by UCSF scientist Krystof Bankiewicz, now a co-founder of Voyager, was done in the 1980s. But so far, those efforts haven’t led to an approved product. Voyager believes a big reason it can succeed where others have failed is
