Health Tips

New Medicines which target diseased cells while leaving healthy cells alone—are transforming the way doctors treat cancer, arthritis, and MS. But are the benefits worth the risks, both
January,2006, Richard Oropeza Jr., now 60, was making coffee in the kitchen of his California home when he felt a sudden tingling in his legs. The sensation went away within 20 minutes, but over the next several weeks it came back twice, along with excruciating headaches and complete paralysis on his left side. Emergency surgery revealed that Oropeza had a malignant tumor the size of an apricot on his brain, and doctors gave him less than a year to live. He underwent six weeks of conventional cancer treatment—radiation and chemotherapy—that sapped his energy and caused debilitating nausea. But the tumor kept growing.
"There's nothing more I can do for you," his doctor told him in September 2006, eight months after his initial symptoms.
"Isn't there anything else we could try?" Oropeza pleaded. "Any clinical trial?"
In fact, there was. The University of Virginia, as part of a Phase II clinical trial, was testing a new "biologic" drug called Avastin—the first drug that could fight his type of aggressive cancer by attacking the blood supply that fed the tumor. But there was also a potential downside: the drug could cause blood clots, hypertension, and joint pain.
Oropeza signed the liability waiver. "I didn't care what the treatment was or its side effects," he recalls. "To me it was worth it."
Almost immediately after Oropeza started intravenous Avastin therapy, his tumor stopped growing. He could walk again and hold things without dropping them. He went back to work part-time, and now, every two weeks—for the rest of his life—he will take Avastin. Without it, he says, "I wouldn't be alive today."
Radical recoveries like Oropeza's are giving biologics a much-hyped reputation as miracle drugs. Biologic medicines are now the fastest-growing class of drugs in the pharmaceutical world; Avastin alone garnered nearly $3 billion in sales in 2008. Many patients today survive cancers once considered a death sentence, and those who suffer from autoimmune diseases such as multiple sclerosis or rheumatoid arthritis can regain full use of limbs once racked by crippling pain and immobility.
So why aren't biologic drugs prescribed more frequently? Two reasons: the drugs are expensive—Avastin can cost up to a staggering $100,000 per year—and their side effects can be devastating. Some biomedical experts question whether our current health care system, with its prescription-drug pricing protocols, is equipped to handle the flood of new biologic drugs coming on the market. Most patients rely on private insurance or Medicare to pay for them (Medicare spent roughly $13 billion on biologics in 2007). A few also qualify for subsidies from the biotech companies that develop the drugs. But many patients simply cannot afford the medicines.
"We cannot ethically defend our system of payment and access the way it is now," says Ruth Faden, Ph.D., director of the Johns Hopkins Berman Institute of Bioethics. "We have a class of expensive drugs that can prolong life, improve quality of life, or, in the case of Herceptin [a biologic used to treat breast cancer], possibly be a cure for some patients. It is indisputable that any patient should have access to these drugs, regardless of income or insurance status.
What makes biologic medicines unique is this: unlike conventional chemical drugs, biologics are produced by living organisms and specifically target human proteins that are involved in disease.
One class of biologics—known as monoclonal antibody biologics—are similar to the antibodies that the human immune system uses to fight off bacteria and viruses, only these antibodies are genetically engineered to target specific cancers. Avastin, which proved so effective against Richard Oropeza's brain tumor, is now also widely used to treat lung, breast, colon, and rectal cancers. Other monoclonal antibody biologics are designed to attack certain proteins (or protein receptors) on the surface of cancer cells and stop their growth. Examples of such protein inhibitors include Rituxan, which is used to treat lymphomas, and Herceptin.

Other biologics alter the function of the immune system by either suppressing or enhancing certain responses. In autoimmune diseases such as rheumatoid arthritis and psoriasis, for example, the immune system overproduces a protein that triggers a buildup of white blood cells, which leads to excessive inflammation and joint damage. Enbrel, Humira, Remicade, and other biologics in this class target that protein, called the tumor necrosis factor, and block its action. Tysabri, a biologic used to treat multiple sclerosis and Crohn's disease, blocks the passage of inflammatory cells into the brain and the spinal cord—and, in the case of Crohn's disease, into the intestines.
"These biologic agents provide a degree of selectivity not achievable with conventional chemotherapy drugs," explains oncologist Oliver Press, M.D., Ph.D., of the Fred Hutchinson Cancer Research Center in Seattle. "Many of [the biologics] can produce dramatic antitumor effects without the toxicity that historically has been associated with chemotherapy and radiation."
Biologic treatments date back to 1982, when recombinant insulin was first approved in the United States for the treatment of diabetes. (A hormone originally derived from the pancreas of animals, insulin is today made synthetically from genetically engineered human bacteria.) Since then, more than 300 biologic drugs, most of them developed in the past five years, have flooded the pharmaceutical market. Today they constitute roughly 25 percent of all new drugs approved by the FDA; by 2014, industry insiders predict, more than half of the top 100 drugs will be biologics.
The growth is fueled in part by their effectiveness. Two 2005 studies sponsored by the National Cancer Institute showed that adding Herceptin to standard chemotherapy reduced the risk of recurrence by 52 percent. A 2004 study published in the New England Journal of Medicine found that adding Avastin to chemotherapy extended life by 4.7 months for those with colorectal cancers. And studies have established that the addition of Rituxan to the standard chemotherapy regimen for certain types of chronic leukemia doubled complete remission rates.

The benefits aren't limited to cancer patients. In a 2008 clinical trial of Enbrel (with the chemical-based drug methotrexate) conducted by the developers of the drug—Amgen and Wyeth Pharmaceuticals—half of patients with moderate to severe rheumatoid arthritis were in remission after one year, compared with 28 percent of patients treated with methotrexate (brand names Rheumatrex and Trexall) alone.

When Pat Novak Nelson of Basking Ridge, New Jersey, was diagnosed with rheumatoid arthritis in 1976, available treatments provided little relief for the inflammatory disease. Starting with a single swollen finger, Nelson developed such overwhelming pain that she had to give up her passions: tennis, volleyball, and softball. She couldn't even play Frisbee with her young son. Back then, treatment for the roughly 1.3 million sufferers of rheumatoid arthritis was aspirin and anti-inflammatory drugs such as Naprosyn (naproxen)—which worked "for a while," Nelson recalls.

Then, in 1998, the FDA approved Enbrel, a biologic drug that blocks the protein receptors that trigger inflammation, swelling, and joint damage. "Without question, biologic agents have had a profound impact on improving the treatment of rheumatoid arthritis," says John Howard Klippel, M.D., president and CEO of the Arthritis Foundation. "It can't cure the disease, but it stops it from progressing."

As promising as Enbrel sounded, Nelson had reservations. "I thought about it for a couple of months because the possible side effects [infections, tumors, headaches] can be nasty," she says. But with no alternatives in the offing, she decided to take the plunge, and now, twice a week, she self-injects Enbrel. "It made a huge improvement in the quality of my life," she says. "I can't remember a day when I suddenly woke up in pain.