On September 11, amid the horror of the terrorist attack on the World Trade Center and the Pentagon, little attention was paid to a medical breakthrough in Rockville, Md. A Food & Drug Administration advisory panel gave its wholehearted endorsement that day to a radically new cancer drug that sends a combination of radioactive isotopes and genetically engineered antibodies coursing through the blood.
Frightening as it may sound to some, the treatment, called radioimmunotherapy, appears to be remarkably safe. The antibodies target tumor cells only and then deliver their lethal payload, leaving healthy cells unharmed. It's not a cure, but the method has proven effective in slowing the progress of deadly non-Hodgkin's lymphoma. In clinical trials using the sickest patients--who usually have only a few weeks to live--radioimmunotherapy has caused partial or complete cancer regression for months at a time in as many as 80% of cases. Not a home run, but a notable base hit against a disease that almost always kills.
The FDA panel's unanimous recommendation of Zevalin, made by IDEC Pharmaceuticals Corp. (IDPH) in San Diego, was an important milestone for radioimmunotherapy. The FDA almost always accepts panel recommendations and is widely expected to approve Zevalin by January. But the Sept. 11 decision also set off a bitter patent dispute between IDEC and its leading rival, Corixa Corp (CRXA) in Seattle, with each company suing the other. Corixa, which completed filing for FDA approval of its radioimmunotherapy, Bexxar, on Sept. 7, argues that Zevalin violates a broad suite of patents Corixa holds along with its marketing partner, GlaxoSmithKline PLC (GSK). IDEC, which took legal action first, is seeking a declaratory judgment that Zevalin does not infringe on anybody's patents. Patent disputes over drugs are common, but legal experts expressed surprise that this one has gone so far. Most such battles are resolved by the parties long before court action is taken.
This time, though, the stakes may be too high for either company to give ground without a fight. Because the two drugs are so similar, many analysts figure that the one that reaches the market first will dominate, bringing in first-year sales of $50 million to $70 million. That would go a long way toward justifying Corixa's $900 million purchase a year ago of Coulter Pharmaceuticals Inc., primarily to acquire Bexxar. Corixa CEO Steven Gillis says his company has patents dating back to 1993 that Coulter licensed from the University of Michigan, where the drug was first developed. "IDEC clearly knew about the patents and listed them in their 10-Q and 10-K reports [as potential risks] but never contacted us," he says.
IDEC, with a reputation to defend as an antibody pioneer, retorts that Zevalin is unique and covered by its own patents. "We seek to show their patents are invalid and we're not infringing," says IDEC CEO William Rastetter. Zevalin also represents a chance for the company to strike out on its own. IDEC won kudos for developing Rituxan, the first successful antibody-based cancer drug, but the lion's share of the financial rewards have gone to marketing partner Genentech Inc. (DNA). That's no small loss considering that Rituxan sales are expected to reach $875 million this year. With Zevalin, IDEC has retained all U.S. rights (overseas rights were licensed to Schering AG). So while Corixa has said it would accept a licensing fee, IDEC is in no mood to pay.
INSIDIOUS. Analysts worry that the patent dispute may slow the marketing of both drugs as well as progress in developing radioimmunotherapies for other cancers. "This isn't good for biotech," says Dr. Mark Monane, vice-president of biotechnology at market researcher Needham & Co. "We're hoping the companies come to a reasonable solution."
The people with the most at stake here are the patients. Non-Hodgkin's lymphoma afflicts more than 50,000 people a year in the U.S. and is the sixth-leading cause of cancer death. It is an insidious cancer of the lymphatic system, which branches into all the organs. Because this network is so vast, the disease can start anywhere in the body and spread quickly, sparking a wild proliferation of white blood cells called B-lymphocytes that eventually crowd out healthy cells. Survival rates from the time of diagnosis range from a high of 10 years to only six months.
Right now, the leading treatment for non-Hodgkin's is IDEC's Rituxan, an antibody that latches onto a bit of protein known as the CD-20 antigen found only on the surface of B-cells. There the drug recruits the immune system to attack the marauding cells. Radioimmunotherapy adds a second line of offense by tethering the antibody to a radioactive isotope. Once the antibody attaches to the cell, the radiation kills it off.
Both Zevalin and Bexxar target the CD-20 antigen and both use similar antibodies. The difference is in the isotope: Zevalin is combined with yttrium-90, while Bexxar contains iodine-131. Some medical experts say yttrium may have a slight advantage in that it ranges over a larger area than iodine, which may make it more effective against larger tumors. That theory has yet to be proven, however. Each isotope also has a different safety profile: Critics worry that Zevalin poses a slightly greater risk to other organs over the long term while Bexxar poses a greater risk to caregivers because some of the radiation leaks out of the body. But doctors believe that with careful monitoring, both dangers are minimal.
COMPLETE RESPONSE. In fact, cancer experts discount the competing arguments made by IDEC and Corixa. "There is no major difference between the two drugs. Both work well," says Dr. Louis M. Weiner, chairman of the Oncology Dept. at Fox Chase Cancer Center in Philadelphia. He believes doctors will be eager to try both. "My experience is that if we have things that work, we use them."
There's no question that the two drugs work. In a clinical study reported in the October issue of the Journal of Clinical Oncology, Bexxar produced a complete response in 20% of 60 extremely sick patients, and nine of those had still not relapsed three years later. Only 3% of patients receiving traditional chemotherapy had a similar response. Clinical trials of Zevalin, which is given along with Rituxan, showed a complete response in 30% of 143 very sick patients, compared with 16% of those given Rituxan only.
The Zevalin data clearly won over the FDA panel. It not only voted to recommend the drug as a treatment for patients who fail to respond to Rituxan, but the panel unexpectedly recommended the drug for patients who fail standard chemotherapy, provided the company does more studies once the drug hits the market.
Next up will be Bexxar, which is expected to receive its FDA panel hearing in December. But Zevalin is almost certain to reach the market first--and Corixa CEO Gillis says he won't try to stop it. Instead, says Gillis, Corixa is seeking a permanent injunction that would remove Zevalin from the market once the lawsuit is resolved. Whoever wins in court, patients are bound to come out on top. By Catherine Arnst in New York, with Arlene Weintraub in Los Angeles