Doctors can’t do much for patients with a rare, aggressive form of Lou Gehrig’s disease, even though researchers are confident they have pinpointed its genetic cause. But now with help from a clever device that’s supposed to deliver RNA-silencing drugs where they couldn’t go before, Carlsbad, CA-based Isis Pharmaceuticals is hopeful it may have found new way to treat the deadly neurodegenerative disease.
This treatment, ISIS-SOD1RX, which Cambridge, MA-based Genzyme has an option to co-develop, is being prepped for its first clinical trial later this year for patients with an aggressive form of amoytrophic lateral sclerosis (ALS). The treatment uses the typical Isis approach, known as antisense, in which the drug is designed to shut down the RNA that enables the production of disease-causing proteins.
The treatment also could blaze a trail for a new mode of delivering antisense drugs for a range of neurological disorders, including ALS, Parkinson’s, and Huntington’s disease. The delivery technology is both scientifically interesting and poses big potential business implications for Isis (NASDAQ: ISIS).
Isis has never been able to pursue these major diseases because antisense molecules are too big to pass through the blood-brain barrier when they are delivered by conventional injection under the skin, which allows the drug to circulate throughout the body. To work around that problem, Isis developed a reformulated version that could be delivered through infusion with a spinal tap device. If this technique works in the upcoming trial, it could offer a potential new approach for a subset of patients with ALS, which is diagnosed in a total of 5,600 new patients each year in the U.S.
“We’re going into a patient population with no other therapies, and it’s an aggressive form of the disease with a life expectancy of less than one year,” says Frank Bennett, Isis’ senior vice president of research. “What excites me is that we have an opportunity to help those patients. We’re optimistic.”
This form of ALS is considered a good test case for the new delivery technology because it involves overproduction of a specific protein called Superoxide dismutase1, which can be toxic to the central nervous system, Bennett says. A traditional small-molecule drug wouldn’t really work if it were made to bind with this enzyme, he says. Isis believes antisense will work better because it will stop the overproduction of the protein in the first place.
Until now, delivery has been the key challenge. Isis scientists have been working on a new formulation that can be used in tandem with new spinal infusion delivery technologies from companies like Medtronic (NYSE: MDT), Johnson & Johnson’s Codman division, and Inset Technologies. The new tools are designed to allow slow, steady infusions of drugs for pain and spasticity, but can be used to deliver other treatments as well, Bennett says. It’s possible that patients can stay on such a system for years, either getting continuous infusions, or possibly intermittent on-off cycles.
If the Isis treatment reaches its goals of safely delivering the antisense drug into the brain, then it could establish a precedent for a couple other delivery-challenged neurology drugs in the pipeline for Huntington’s and Parkinson’s, Bennett says. Those programs, which haven’t yet entered clinical trials, are funded by a couple of well-known patient advocacy groups, the Cure Huntington’s Disease Initiative, and the Michael J. Fox Foundation for Parkinson’s Research. Naturally, the financial prospects of developing drugs for those more common diseases could add up to bigger rewards for Isis as a company.
Despite Isis’ optimism, Bennett sounded like he didn’t want to get too carried away, and emphasized that all the programs are still at early-stages of development: “We’ll keep our fingers crossed,” he says.