Merck & Co. is teaming with AstraZeneca Plc (AZN) to test two cancer drugs as a single therapy, leading a wave of alliances among rivals spurred by new evidence that multiple genetic triggers can lead to tumor growth.
At least eight drugmakers have joined forces to share treatments since Merck, of Whitehouse Station, New Jersey, and London-based AstraZeneca began their effort -- now entering early efficacy tests -- in 2009, Bloomberg Businessweek reports in its June 20 issue. In the past, companies seeking a therapy to complement theirs would take years to craft it internally, said Gary Gilliland, Merck’s head of oncology. Now, they are increasingly reaching out to competitors to boost the attack on cancer and speed time to market, he said.
Many new drugs work for a short time before tumors mutate and become resistant, limiting survival advances to months, not years. Only by hitting cancer from multiple angles may doctors hold it in check longer, said George Sledge Jr., an oncologist at Indiana University’s Cancer Center in Indianapolis.
Doctors need “a magic shotgun loaded with pellets aimed at multiple targets in multiple pathways,” not just a magic bullet, said Sledge, immediate past-president of the American Society of Clinical Oncology, at the organization’s annual meeting, which ran through June 7 in Chicago.
Bristol-Myers Squibb Co. (BMY), based in New York, and Roche Holding AG (ROG) of Basel, Switzerland, announced June 2 their collaboration on two skin cancer therapies, and plan to begin studies on a combination by the end of the year.
Seeking a Partner
In 2010, Paris-based Sanofi concluded that its drugs targeting a molecule called PI3K may work better in combination with a MEK inhibitor, developed by Merck KGaA (MRK), of Darmstadt, Germany. In December, the companies agreed to develop the drugs jointly. The first patients were enrolled in studies in May, said Debasish Roychowdhury, Sanofi’s chief oncology officer, in an interview.
GlaxoSmithKline Plc (GSK) and Novartis AG of Basel, Switzerland, started testing a combination of the companies’ drugs in April 2010 in patients with advanced solid tumors.
“I see in the future more and more collaboration between pharmaceutical companies,” said Paolo Paoletti, president of the oncology unit at London-based Glaxo. “At the end of the game it is the right thing to do for patients.”
It still isn’t common for the industry, however.
“Working together is not something we’ve typically had to do,” said Deborah Dunsire, chief executive officer of Tokyo- based Takeda Pharmaceutical Co.’s Millennium Pharmaceuticals. Her company is seeking collaborations with several others that may be announced in the next year, she said. She wouldn’t identify them.
‘Makes Us Nervous’
“Now we have to collaborate on drugs that are new, proprietary and not yet approved, which makes us all nervous,” Dunsire said in an interview. “But we can’t continue throwing out potentially good drugs because they don’t have enough activity as a single agent.”
Merck and AstraZeneca’s trial combines Merck’s drug against a protein called AKT, which promotes cancer progression, with AstraZeneca’s compound against the related MEK molecule. The trial yielded safety data at the cancer meeting.
Merck also has been holding talks with multiple other companies about additional collaborations, Gilliland said.
“Our perspective is if we have a mechanism we think is complementary to what another company has, let’s bring the things together,” he said. “We hope combinations will cure cancer, but at a minimum put cancer in abeyance for a long period of time.”
A revolution in biology has triggered an explosion of compounds targeting genes and mutations responsible for cancer’s growth. Since 1998, when Roche’s Herceptin was approved for breast tumors expressing high levels of the HER2 protein, more than two dozen targeted cancer treatments have reached the market.
About 800 targeted cancer medicines aimed at about 300 genes linked to the disease are now in development, John Mendelsohn, president of the University of Texas M.D. Anderson Cancer Center in Houston, said in an interview.
The move to combinations is “an admission,” that single- drug targeted therapy hasn’t been the cancer panacea that doctors once hoped for, said Leonard Saltz, an oncologist at Memorial Sloan-Kettering Cancer Center in New York, in an interview. Combining drugs is “a fallback position,” when one medicine doesn’t do enough.
Still, combinations of targeted drugs can make things worse, he said, citing a February, 2009 study in the New England Journal of Medicine that found combining Erbitux from Eli Lilly & Co. and Avastin from Roche, along with powerful chemotherapy drugs, resulted in advanced colon cancer progressing faster.
“None of us saw that coming,” said Saltz.
Combinations of targeted therapies would not only boost the size of the oncology market, already the biggest pharmaceutical category with sales of $56 billion worldwide, they would also raise costs, said Les Funtleyder, an analyst at Miller Tabak & Co. in New York. New cancer therapies are among the most expensive drugs, with treatments such as Bristol-Myers’s Yervoy costing $120,000 for a single course of four doses.
“The elephant in the room is the more drugs you combine the more expensive it gets,” Funtleyder said in an interview. “There could be financial pressure down the road. Patients and payers are looking for value for money. Ultimately, these combinations are going to have to prove their worth.”
“Companies that recognize they can’t have a monopoly on all of the best drugs and diagnostics will recognize that risk- sharing is in the best interest of patients, the health-care system and, ultimately, the companies that do it right,” he said in an e-mail.
U.S. regulators are preparing for the transformation, meeting with companies and putting a new emphasis on early laboratory work, said Richard Pazdur, director of the Food and Drug Administration’s Office of Oncology Drug Products, in an interview. The agency issued proposed guidelines in December clarifying when novel drugs can be tested simultaneously before they are proven effective alone. The agency plans to issue final standards by year’s end.
Cancer has shown itself to be so complicated that two-drug collaborations may not be enough, said Sledge, of the cancer doctors’ group.
Drug companies and research hospitals may need to join together in a giant network to test numerous possible drug combinations. Doctors would then be able to mix drugs from multiple companies based on gene tests indicating which cocktails may work best for each patient, Sledge said.
“I currently don’t see any company that will be able to carry it out by themselves,” he said. “We are talking about an entirely different system than what we have now.”
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