Biogen Idec is the world’s biggest maker of drugs for multiple sclerosis, and it wants to keep things that way. But every drug that’s born eventually dies, and the last remaining patents on Biogen’s biggest-selling drug, interferon-beta1a (Avonex), run out in 2011 and 2013. To protect this $2.2 billion-a-year MS franchise—which generates more than half of Biogen’s sales—the company has cooked up a modified version (with a fresh new patent, of course). The new drug is supposed to last longer in the bloodstream, require fewer shots, and maybe even work better.
The idea—attach a polymer to the end of this type of interferon protein—has been tried by chemists for years with no luck, but it would be a big deal if Biogen or anybody else could find a way to make it work. Biogen is so jazzed about this concept that it is leapfrogging from the first phase of clinical trials to the final stage. I spoke with Biogen’s president of research and development, Cecil Pickett, this week for more insight into the company’s strategy in pursuing this “pegylated” version of its workhorse interferon drug.
The current batch of interferons, the standard of care for MS, are effective at reducing flare-ups from the chronic neurodegenerative disease, generating about $4 billion a year in revenue for Biogen, Bayer, and Merck KGaA. But patients say they can be a nuisance. The drugs cause flu-like symptoms and suffer from peaks and valleys of concentration in the bloodstream that are thought to weaken their effect and require them to be taken with more than one injection a week. Many patients struggle to stick with their meds, especially when it’s hard to tell for sure when the drugs are working.
There is a precedent for making a pegylated version of interferon—a related molecule for hepatitis C called interferon alpha. Modified forms of this drug, for hepatitis C, have been shown to boost their effectiveness and increase convenience for patients, and have become billion-dollar franchises for Roche and Schering-Plough. Since multiple sclerosis treatment is becoming increasingly competitive with convenient oral drugs from Novartis and Merck KGaA emerging in late-stage clinical trials, Biogen sees the long-lasting interferon-beta as an important way to defend its turf. There are at least two venture-backed startups, Seattle-based Allozyne and San Diego-based Ambrx, working on longer-lasting interferons for MS, but neither has yet entered clinical trials. Biogen believes it is still in the lead, and it might be able to strengthen its grip on the market by combining the longer-lasting interferon with an oral MS drug of its own, Pickett says.
“We felt comfortable with the dose and response we saw in the Phase I study,” Pickett says. “I think we’re in the lead, and given the expertise we have in MS and our ability to make these kinds of molecules, I’m bullish about this.”
Pickett says he’s been an in-house advocate for this program since he joined Biogen in September 2006, because he’s “biased” from his previous experience at Schering-Plough. That Kenilworth, NJ-based drugmaker (NYSE: SGP) attached a polymer to a different kind of interferon, the alpha variety, and turned it into a $914 million hit marketed as PEG-Intron for hepatitis C. What’s more, that compound works in combination with an oral hepatitis C drug, ribavirin. That’s gotten Biogen thinking about one day combining its long-lasting interferon beta with BG-12, an oral MS drug it has in development, Pickett says.
Chemists have traditionally had a hard time making a long lasting interferon beta, because attaching polymers in standard manufacturing techniques is easier said than done. Past techniques caused the polymer to attach to different parts of the protein, rendering it an inconsistent product in the vial, which is a big no-no when it comes to passing muster with FDA inspectors. So Biogen’s secret was to find a way to attach the polymer in a consistent place on an amino acid at the end of the protein, Pickett says.
Biogen will set out to prove this idea in a clinical trial of 1,260 patients called Advance. It will compare two different doses of pegylated interferon—one given every other week, the other given once a month—versus patients on a placebo. The goal will be to reduce the relapse rate from MS for a full year. If this trial is able to recruit patients on schedule, it could produce results in 2011, Pickett says. Regulators at the FDA and European Union have agreed that success in the trial could lead to marketing approval, he says.
Biogen presented a few more details on this program Wednesday at its R&D day with financial analysts. The company has made this drug into a pre-filled syringe, that can be injected just under the skin, instead of deeper into the muscle, said Al Sandrock, Biogen’s senior vice president for neurology R&D. This way, it ought to be especially convenient for patients, and more likely they will stick with the required dosing schedule, Sandrock said.
As confident as Biogen sounds about this program, Sandrock reminded the audience how humbling this business can be. Even though Avonex has been on the market since 1996, scientists still don’t know some very basic things about it. “To be honest, we don’t know exactly how interferon works,” said Sandrock, who’s no dummy (he’s an assistant professor of neurology at Harvard Medical School.)
Scientists think the interferons may interfere with the trafficking of immune system cells that go haywire and start attacking the myelin coating around nerve cells in people with MS, Sandrock says. It’s also possible the interferon may be decreasing the effect of inflammatory proteins called cytokines, or boosting the activity of anti-inflammatory cytokines, Sandrock said.
Whichever way the drug really works, it’s generally a pretty safe bet to take an existing biotech drug and add pegylation to it. The company has 20 programs in Phase II or Phase III clinical trials, and Pickett knows that quite a few will go bust. Just a couple weeks ago, he was stumped by the failure of rituximab (Rituxan) in a pivotal trial of patients with lupus of the kidneys, despite loads of encouraging evidence from earlier studies.
So while he reminded me he’s bullish about pegylated interferon beta’s prospects, there’s no such thing as a sure bet in biotech. “I really hope our late-stage programs have a batting average of 70 percent,” Pickett says.