The biggest clinical trial news of 2015 so far, arguably, was a report from Biogen Idec (NASDAQ: [[ticker:BIIB]]) about a drug meant to do something never done before: repair nerve damage in multiple sclerosis patients and possibly reverse the course of the disease.
The news was also quite ambiguous. In a Jan. 8 release, the company deemed the results “positive,” even though the trial, dubbed RENEW, didn’t prove statistically significant for the most important measure and showed no improvement in two other measures. The full data set is to be unveiled at an unspecified future medical conference, Biogen Idec said.
In other words, the results were not the clear-cut, move-this-drug-ahead-now kind that a company, its investors, and most importantly, patients in dire need of new treatments would like to see. Yet it provoked responses like this, from Ari Green, a neurologist at the University of California, San Francisco, who treats MS patients: “The progress they’ve made is an important step in right direction. Whether this specific agent is one with adequate efficacy and safety, we have no idea.”
That’s because this kind of nerve repair—called remyelination—has never been tried in humans before. Observers like Green were happy there were no safety problems and even a glimmer of positive effect in patients.
Biogen already has an industry-leading franchise of MS drugs such as interferon beta-1a (Avonex), natalizumab (Tysabri), and dimethyl fumarate (Tecfidera). They all help tamp down the immune system’s attack, but they don’t reverse existing damage to myelin, the fatty white protein that forms nerve sheaths and also constitutes about half the human brain.
Why the immune system identifies myelin as a pathogen and chews it up, no one knows. But Michael Gilman, the CEO of Padlock Therapeutics and a former Biogen research executive, says there are two schools of thought. One is that MS is an “outside-in” disease; the brain develops an immune response to a virus or infection that somehow goes into overdrive. The other theory is that it’s an “inside-out” disease; the primary defect or injury is in the brain, and the ensuing inflammation is a reaction to that injury.
Regardless of the reason, however, people with MS know the results: A nervous system that goes haywire, sometimes slowly, sometimes in bursts, causing all sorts of symptoms from numbness to vision loss to slurred speech and worsening motor coordination. It’s unpredictable, and it’s irreversible.
“People working in MS understand the paradigm shift of launching drugs that directly treat the damaged tissue,” said Tassie Collins, vice president of translational medicine at the Myelin Repair Foundation in Saratoga, CA, a nonprofit research group with its own R&D program. “That’s a biological paradigm shift.”
Collins sees a powerful one-two punch with current treatments. As those drugs keep the immune system in check, a myelin repair treatment would help the body rebuild the nerves.
Biogen’s test was the first to show something. The company’s R&D chief Doug Williams, whom Xconomy interviewed at the J.P. Morgan Healthcare Conference in San Francisco, said, “We’ve now demonstrated ‘proof of biology’—that we can get remyelination in man—which is something that’s never been demonstrated before.”
Major drug companies don’t often enter the middle stages of clinical development—the just-completed trial was Phase 2a—while learning on the fly about the biology of a disease. It’s a recipe for lots of time and money spent pursuing a very risky goal, which tends to make short-attention-span shareholders nervous. But that’s what Biogen is doing.
“In new areas, where we’re pioneering biology, part of it is accepting that you have to do basic work on the clinical side too,” said Williams, who joined Biogen four years ago.
With myelin repair, the risk and reward are both high. Biogen’s big bet is on a monoclonal antibody, dubbed BIIB-033, that blocks a protein called LINGO-1 and, in animal tests, both encourages remyelination and restores health.
In the Phase 2a data released earlier this month, Biogen tested BIIB-033 in patients with acute optic neuritis (AON), an attack on the optic nerve that is often the first acute symptom to afflict a MS patient. (UCSF’s Green says 25 to 30 percent of all first attacks of MS are AON, and that 80 percent of all MS patients at some point suffer an AON attack.)
Biogen’s idea was to get its anti-LINGO drug into patients soon after an acute attack to see if the optic nerve could recover. And here’s where the top-line data get tricky.
Biogen reported that in 34 percent of the people in the study, electric signals moved more freely through the nerve after treatment—a measurement of the nerve working better. But the study wasn’t designed
