When Two Cancer Drugs Are Better Than One

Since 1998, when Roche Holding's Genentech won approval for the first of a new generation of personalized cancer medicines, drugmakers have rushed to develop compounds targeting specific genes and mutations responsible for cancer's growth. About two dozen targeted drugs have reached the market. An additional 800 medicines aimed at about 300 different genes are in development, says John Mendelsohn, president of the University of Texas MD Anderson Cancer Center. The methodology has produced some of the most costly pharmaceuticals ever: Erbitux, a colon cancer drug by Bristol-Myers Squibb (BMY) and Eli Lilly (LLY), for instance, costs $40,000 for a typical 16-week regimen. But recent research has shown that even targeted drugs often extend life only for a matter of months before cancers find ways to mutate beyond their reach.

So Big Pharma is embracing a new approach, using two experimental drugs that simultaneously attack cancers in different ways. This double-teaming keeps cancer cells off-balance, slowing their ability to adapt to drugs and hopefully impeding their ability to spread. Explains George Sledge Jr., an oncologist at Indiana University's cancer center: To keep cancer in check longer, doctors need "a magic shotgun loaded with pellets aimed at multiple targets in multiple pathways," not just a magic bullet. Besides the health advance, doubling up the use of these pricey treatments could be a real tonic for makers of cancer drugs, which at $56 billion in sales annually comprise the single biggest pharmaceutical segment.

Merck (MRK) and AstraZeneca (AZN) in 2009 became the first rivals to join forces to test two experimental cancer drugs as a single therapy. They're initially targeting lung cancer. Their trial combines Merck's drug, which works against a protein called AKT that promotes cancer progression, with AstraZeneca's compound against a related molecule that helps tumors grow. In the past, companies seeking a therapy to complement their own would craft it internally, says Gary Gilliland, Merck's head of oncology. That could take years. Now, drugmakers are increasingly reaching out to rivals to speed the time it takes to get therapies to market. "Our perspective is if we have a mechanism we think is complementary to what another company has, let's bring the things together," he says. "We hope combinations will cure cancer, but at a minimum put cancer in abeyance for a long period."

More than a half-dozen companies have joined forces to share drugs. In 2010, Sanofi concluded that its drugs targeting a cancer-related molecule called PI3K may work better in combination with a compound developed by Germany's Merck KGaA. In December the companies agreed to develop the drugs jointly. Bristol-Myers in June paired its Yervoy with another skin cancer therapy from Roche; the companies plan to begin combo studies by yearend. (Yervoy is the only combo component drug that's been approved for sale so far.)

"I see in the future more and more collaboration between pharmaceutical companies," says Paolo Paoletti, president of GlaxoSmithKline's (GSK) oncology unit, which is testing one of its cancer drugs along with a complementary drug from Novartis (NVS). "At the end of the game, it is the right thing to do for patients."

That's a shift for drugmakers. "Now we have to collaborate on drugs that are new, proprietary, and not yet approved, which makes us all nervous," says Deborah Dunsire, chief executive officer of Takeda Pharmaceutical's Millennium Pharmaceuticals. "But we can't continue throwing out potentially good drugs because they don't have enough activity as a single agent." How combo drugs will be marketed will depend on whether regulators approve them as separate compounds or a single treatment.

There are concerns about combos. "The elephant in the room is the more drugs you combine, the more expensive it gets," says Les Funtleyder, an analyst at Miller Tabak. "Patients and payers are looking for value for money. Ultimately, these combinations are going to have to prove their worth."

The bottom line: Drugmakers are collaborating to test combinations of genetically targeted cancer drugs in hopes of boosting survival rates.

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