A drug that actually slows or reverses the brain damage inflicted by Parkinson’s disease, rather than just alleviates its often debilitating symptoms, remains elusive. But Prevail Therapeutics, a startup just launched in New York, has become the latest to try.
This morning, the Silverstein Foundation, a nonprofit organization formed by OrbiMed partner Jonathan Silverstein, announced the formation of a new startup in New York called Prevail Therapeutics. Headed by Columbia University neurology professor and Parkinson’s researcher Asa Abeliovich, the startup has launched to press forward with a gene therapy, and possibly other approaches, for a genetically-defined subset of people with the condition.
Prevail has a deal in place with RegenXBio (NASDAQ: RGNX) to use a tool used in gene therapy that shuttles genetic instructions into the body to fix a disease-related malfunction. Prevail can now use the delivery tool, a type of engineered virus, to develop a gene therapy for Parkinson’s or other neurodegenerative diseases. The goal is to introduce a working copy of a gene that is mutated in people with a rare genetic form of Parkinson’s. The hope is that the new gene would alter the progression of the disease.
The startup is the first industry investment for the Silverstein Foundation, which formed earlier this year to fuel Parkinson’s research. CNBC reported Wednesday morning that Silverstein, a longtime life sciences investor at OrbiMed, started the foundation after being diagnosed with an aggressive form of Parkinson’s. According to its website, the foundation has given grants to the Michael J. Fox Foundation, the Parkinson’s Institute and Clinical Center in San Francisco, and Columbia University.
Abeliovich, whose research at Columbia has been focused on the genetics underlying Parkinson’s, worked with OrbiMed when he co-founded Alector, an OrbiMed-backed neurological drug developer in San Francisco (he’s currently that startup’s chief innovation officer). The OrbiMed connection led Abeliovich to join the Silverstein Foundation’s scientific advisory board, and eventually to discussions about forming new companies to combat the disease. The first is Prevail.
“He’s put together a real ‘SEAL team’ to try to figure out how we can advance things” against Parkinson’s, Abeliovich says of Silverstein.
Both the Silverstein Foundation and OrbiMed are investors in Prevail. Abeliovich wouldn’t say how much has gone into the company so far. The Silverstein Foundation didn’t immediately respond to a request for comment Wednesday.
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.
Levodopa has been the standard of care for Parkinson’s since the 1960s. While much remains unknown about the disease’s underlying biology, 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 huge difference. It helps nerve cells make dopamine, which in turn helps patients manage symptoms and function normally for a longer period of time.
The problem is, over time, patients’ responses to levodopa start to decrease. To compensate, patients boost their levodopa doses, but that can cause dyskinesia, or uncontrollable, spastic movements.
The good news is over the past few years, new drugs have emerged to help combat these and other symptoms. In 2016, Acadia Pharmaceuticals (NASDAQ: ACAD) won FDA approval of a drug, pimavanserin (Nuplazid), meant to reduce hallucinations associated with Parkinson’s. The agency is also currently reviewing two new Parkinson’s treatments. One, from Adamas Pharmaceuticals (NASDAQ: ADMS), called ADS-5102, is meant for levodopa-induced dyskinesia and could be approved by August 24. Acorda Therapeutics (NASDAQ: ACOR) filed for approval of an inhalable form of levodopa (branded as Inbrija) in late June, and expects to know by September whether the FDA will approve the treatment.
Gene therapy, first attempted in the 1980s and so far not approved for clinical use, is among the methods also currently being tested. Voyager Therapeutics (NASDAQ: VYGR), a Cambridge, MA, has a treatment, VY-AADC01, that doesn’t stop or slow Parkinson’s but is meant to help advanced patients start responding to levodopa again after the drug’s effects wane. Early results have been promising so far, but the therapy, in Phase 1 testing, still has a long way to go.
There has been “a lot of progress with therapeutics that help patients’ symptoms, that help them function, and obviously those are very important,” Abeliovich says. Unfortunately, he says, because of the disease’s biological complexity, “most” of the drugs in experimental testing go after symptoms, not the disease itself.
Prevail is. Though it hasn’t disclosed much about itself yet, the company is focusing, Abeliovich says, on therapies that can slow, stop, or reverse Parkinson’s for a subset of patients with a rare, aggressive, genetic form of the disease associated with a mutation to the GBA1 gene. About 10 percent of patients with Parkinson’s have this form, according to the Michael J. Fox Foundation, and the gene’s association with the disease was discovered in 2004.
Other efforts to battle Parkinson’s in patients with GBA mutations are underway. Sanofi began a Phase 2 trial in February of an experimental drug called GZ/SAR402671, which at the time Sanofi noted was the first industry-sponsored test of a drug in a genetically-defined group of Parkinson’s patients. Allergan nabbed an option to acquire Lysosomal Therapeutics (LTI) in January; LTI’s lead program, LTI-291, is meant to slow the progression of Parkinson’s in patients with GBA1 mutations.
Prevail is starting out with a gene therapy for this group. The company plans to try other disease-altering approaches as well, though Abeliovich, the firm’s full-time CEO, wouldn’t specify what they are at this point.
“There’s been tremendous progress in understanding the human genetics of Parkinson’s, and it’s really pushed the field,” he says. “We feel like we can take advantage of this information.”
Alexion Pharmaceuticals (NASDAQ: ALXN) co-founders Leonard Bell and Steve Squinto have both joined Prevail’s board of directors, Abelovich says.