Biogen Idec’s scientists have a vision for regenerative medicine, and it has nothing to do with what’s been written and said about embryonic stem cells.
Deep in Biogen’s pipeline, on the verge of entering clinical trials, are a pair of regenerative medicines that the company hopes will become trailblazers in the world of neurological diseases. I got the rundown on one candidate for multiple sclerosis back in August. Yesterday I gathered more about the other contender, neublastin, for neuropathic pain.
This second candidate grabbed scientists’ attention a year ago, when Biogen researchers published experimental data in Nature Neuroscience with collaborators at the University of Arizona and Tufts University. They found that when rats suffered damage to a bundle of nerves that feed into the spinal cord, then got neublastin injections, the nerves grew back into the spinal cord and, importantly, restored the rats’ ability to feel sensations in their paws and perform complex movements like grabbing onto objects. After a half-dozen shots over 11 days, the effectiveness endured for six months. This ability to restore function came after studies had already shown neublastin can relieve chronic neuropathic pain in animals.
If anything like this can be repeated in people—always a big if—the business opportunity would be big. An estimated one in 100 people in the U.S., or about 3 million people, suffer from nerve dysfunction that causes neuropathic pain. This is the mysterious kind of pain many people suffer, like back pain, that doesn’t respond to conventional analgesic or narcotic pain relievers. Pfizer’s gabapentin (Neurontin) became a $2.4 billion drug in 2003 largely from treating this type of pain, even though it was never explicitly approved by the FDA for that purpose.
“There’s a high level of excitement here. This is beautiful biology,” says Al Sandrock, Biogen’s senior vice president of neurology R&D, and an assistant clinical professor of neurology at Harvard Medical School. “These are admittedly high-risk programs, but if we succeed in restoring nerve function, there are not many other people who are working on this.”
Biogen has been eyeing this field for more than a decade. The company got an exclusive license to develop neublastin from NsGene, a Danish company that discovered the protein in 1998 from research into a family of proteins called glial-derived neurotrophic factors (GDNF). These proteins work to help keep nerve cells alive. Neublastin is particularly interesting, because it interacts with cells that sense pain and temperature changes, Sandrock says.
When these “sensory neurons” get injured, people feel neuropathic pain, Sandrock says. One leading theory is that these pain-sensing cells turn hyperactive, which might explain why people feel back pain when sophisticated imaging tools like MRI can’t detect an obvious tissue injury. Another is that when these sensory neurons get damaged, the normal feeling of “touch” gets converted erroneously into a pain sensation, Sandrock says. Injecting a genetically engineered copy of the neublastin protein may work against this condition by decreasing the hyperactive firing of damaged neurons, or it could promote “good remodeling” of nerve cells, Sandrock says.
Of course, this all has a long, perilous road to travel to generate proof of the concept in human clinical trials. Only one in 10 drugs that enters clinical trials ever becomes an approved product, and this program sounds riskier than the usual drug that’s following a well-trod path. It’s been a year since the Nature Neuroscience paper, and Biogen isn’t yet in the clinic, although it says it is in discussions with the FDA about putting together an application to start trials. “We’re close to the going to the clinic,” Sandrock says.
Some fundamental things still need to be answered to see if this can become a practical drug. The product is being designed to be delivered intravenously, or through an injection patients can get under the skin, Sandrock says. The animal study called for six injections over an 11-day period, and then saw a lasting benefit for the duration of the study, six months. The company is still discussing what sort of dosing schedule might be required for people, Sandrock says.
Other big drugmakers have their eyes on regenerative medicines. San Diego-based Ceregene recently failed in a mid-stage clinical trial of a gene therapy that was made to stimulate growth of neurons to treat Parkinson’s disease. Swiss drug giant Novartis has tested an antibody that interferes with Nogo, a protein that puts the brakes on natural development of new neurons after a spinal cord injury. Another pharma giant, Johnson & Johnson, is pursuing a competing approach to neublastin for neuropathic pain, although Biogen is thought to be ahead in development, Sandrock says.
Most notably, Menlo Park, CA-based Geron (NASDAQ: GERN) got permission from the FDA in January to start the world’s first clinical trial of an embryonic stem cell therapy for people with spinal cord injuries. Biogen’s treatment may never see this kind of intense media attention because it doesn’t depend on the controversial cells. But the goal behind it—regenerating the damaged nerve tissue to restore the lost function—is similar.
“You may not need to come in to the doctor forever,” Sandrock says. “We got long-lasting restoration of sensory function in preclinical studies. That’s the potential value of a drug that’s disease modifying.”