Biogen Idec’s Dream: Antibodies That Kill Two Birds With One Stone
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if they are given at the same time, Manning says.
So Biogen scientists have been working on a way to fuse together an antibody that can recognize two targets at once. This bispecific antibody doesn’t look like a classic Y-shaped antibody, but rather, more like an X-shaped double antibody that recognizes a different target on each end. Without getting too technical, this is basically easier said than done. “It’s a molecular biology challenge,” Manning says. “People have been working on this for 25 years.”
Many other companies have tried this, without any big commercial success. Manning handed me a review article published in the journal Pathobiology in 2007 that has a handy chart listing drug candidates from Micromet, MedImmune, Trion Pharma, Fresenius Biotech, and Medarex. Many past efforts have been hampered by laborious production procedures, according to the Nicolas Fischer and Olivier Leger of Switzerland-based NovImmune, who wrote that review.
One of the keys to getting this right is making the new bispecific antibodies stable, and practical to scale up in consistent, large-scale commercial batches, Manning says. This is one step where companies often fall down, because of a lack of communication from the basic researchers and biotech drug manufacturing experts, but Manning insists that at Biogen those two groups are on the same page. If anything, Manning says, the manufacturing group is “more enthusiastic” than the science group he heads.
How far along has this work progressed? Biogen has selected two leading candidates for clinical trials, and expects to push them into human tests in 18 to 24 months, Manning says. When I pressed him for details about these drugs, he started getting more tight-lipped.
But I was able to gather some tidbits. The first bispecific antibody candidate is being developed for an immunologic disease by blocking one “well-validated target” plus a second target that’s novel to Biogen, Manning says.
The next product candidate is for cancer, Manning says. Biogen is hopeful about this drug because it essentially has two ways of more effectively shutting down the insulin-like growth factor receptor. Biogen already has a more traditional antibody against this target in clinical trials, as does Pfizer, but neither one of them causes the complete blockade of the target that the bispecific antibody does in lab experiments, Manning says. That’s important because partial blockage of the target is thought to be one reason tumors often find ways to resist new targeted treatments over time, Manning says.
Of course, a huge amount of work will have to be done to show these drugs are safe. Drugs that block TNF and IL-6 independently are already associated with making patients vulnerable to infection, and the FDA will surely watch for any sign that a bi-specific antibody makes patients any more susceptible.
But if Biogen has success with its first two bispecific antibody candidates, there will be some strong lobbying within the company to develop more of these kinds of drugs. They may not ever completely replace the original monoclonal antibodies like rituximab, but they could eventually be on an even footing, Manning says. “Our goal is to have half of all biologics move to this platform,” he says.