Pharmaceuticals

Big Pharma Bets on a Novel Cancer Cure


Drug companies have long hawked cancer treatments that either kill tumors outright with chemotherapy or use pricey medicines to block the mutated genes that fuel cancer's growth. Recently, drugmakers including GlaxoSmithKline (GSK), Eli Lilly (LLY), and Novartis (NVS) have begun chasing a third approach: reprogramming the aberrant DNA that can turn cells cancerous in the first place.

These new drugs exploit the epigenome, the molecular machinery that cells use to turn genes on and off, telling them when to produce proteins that carry out most functions of life. Celgene (CELG) last year generated $534 million in revenue on its epigenetic compound Vidaza, which adds months of life for patients with a leukemia-type disorder. The approach has led to three other approved blood cancer drugs from Japan's Eisai, Merck (MRK), and Celgene.

The bigger payday will come from big-ticket drugs that treat the millions who suffer from more common—and lucrative—forms of cancer, such as those affecting the lungs, breasts, or prostate. In January, Epizyme, a company co-founded by Nobel laureate H. Robert Horvitz, agreed to a deal worth up to $650 million with GlaxoSmithKline to search for epigenetics drugs for cancer. Novartis, GlaxoSmithKline, Lilly, and at least four venture-backed startups are also racing to devise cell-reprogramming drugs for more prevalent tumors. "Every major company I know of has a program" in epigenetics, says Jean-Pierre Issa, an oncologist at University of Texas MD Anderson Cancer Center in Houston.

One reason: Cancer medicines are the world's top-selling drug category, with $22.3 billion in U.S. sales last year, up from $15.8 billion in 2006, according to researcher IMS Health. A hit compound can generate huge sales quickly. The last new approach to cancer—targeting mutated or overactive genes—led to Gleevec, a leukemia drug sold by Novartis, and Pfizer's (PFE) Sutent for kidney cancer. Both topped $1 billion in annual sales within five years of their debuts.

Scientists since the 1980s have focused on cancers caused by DNA damage, such as the harm caused by smoking. Stephen Baylin, a cancer biologist at Johns Hopkins University, says that new research has found that defects in the epigenetic control molecules may be as important a cause of cancer.

Researchers have discovered hundreds of molecules that control genetic bar-code labels on DNA. Normally, these codes help stem cells develop a specialized identity, says C. David Allis, co-founder of Constellation Pharmaceuticals. In cancer, some of the code appears to be altered. For example, epigenetic molecules are damaged in 60 percent of patients with pancreatic neuroendocrine tumors. Another molecule is abnormal in 41 percent of cases of kidney cancer. While scientists aren't certain just how epigenetic medicines work, they appear to reactivate so-called tumor suppressor genes. With epigenetic drugs, "the therapeutic concept is to revert those bar codes back to normal," says Jonathan M. Yingling, vice-president for cancer research at Lilly.

The bottom line: More than $22 billion is spent on cancer drugs annually in the U.S. Big Pharma is hopeful new epigenetic medicines will lift that tally.

Langreth is a reporter for Bloomberg News in New York.

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