Biotech Has a Strong Lineup Heading Into the New Year
Biotechnology, an industry that has had more than its share of hype and disappointment, enters 1999 with a large number of promising medical products in development. Several are expected to complete crucial tests or be sent to the Food and Drug Administration for marketing approval in the coming year.
The biotech drugs farthest along include several artificial antibodies that target cancer or dampen a hyperactive immune system in diseases such as rheumatoid arthritis and asthma. Other products help bones heal after severe breaks or deliver toxins to cancer cells. There’s even a diarrhea treatment that was extracted from a brew made by medicine men in the Amazon rain forest.
Although there is no certainty that any of these will get the FDA’s blessing, the quantity of biotech drugs nearing the end of testing is impressive.
“For the first time, there are a huge number of products in the final stages before being submitted for FDA approval,” said John Sterling, managing editor of Genetic Engineering News.
In a survey of the industry, the Pharmaceutical Research and Manufacturers of America Assn. earlier this year identified 350 biotech medicines in various stages of human testing, more than a third of them for treating cancer. Almost all of the drugs have been in development a decade or more.
The new year, like the last, is likely to be one in which genetically engineered antibodies play a major biotech role.
Two decades ago, British scientists discovered a way to produce purified mouse antibodies in large quantities. From the start, there was speculation that these “monoclonal antibodies” would have wide application in the fight against human disease by attacking cancer cells, microbes or viruses. But early results were disappointing, because the patients’ own immune systems saw the mouse antibodies as foreign and neutralized them.
Scientists have since discovered methods for engineering hybrid antibodies that are part mouse but mostly human--that is, human enough to fool the patient’s immune system and powerful enough to have an impact on the patient’s disease.
Dr. Robert Kirkman of Protein Design Labs in Fremont, Calif., which developed a method used to produce several of the new antibody products, counts seven drugs on the market that use this new technology, with many more in development. Among the disorders targeted: multiple sclerosis, rheumatoid arthritis, ovarian cancer and psoriasis.
“Right now about 25% of products in development [by biotechnology companies] are monoclonal antibodies,” Kirkman said.
Some of the first drugs to reach the market: IDEC Pharmaceuticals’ Rituxan for non-Hodgkin’s lymphoma and Genentech’s Herceptin for certain types of advanced breast cancer.
In some cases, poisons can be attached to the artificial antibodies, creating drugs that act like guided missiles, moving into pockets of tumor cells and killing them. Both IDEC and Coulter Pharmaceutical are racing to test and market radioactive antibodies for treating lymphoma.
Another of the new antibodies neutralizes a naturally occurring chemical, immunoglobulin E (IgE for short) that plays a central role in asthma and hay fever. Genentech, Novartis and Tanox Biosystems are jointly developing the anti-IgE antibody. According to Genentech, testing shows that the drug is effective in reducing allergic symptoms such as itching, sneezing and watery eyes.
This year, Centocor won approval for a genetically engineered antibody called Remicade for use in treating Crohn’s disease, a severe bowel disorder that affects an estimated 400,000 Americans. The drug works by neutralizing tumor necrosis factor, a substance produced by the body that plays a key role in stimulating normal immune defenses.
The blocking of this substance may allow doctors to alter the course of a number of diseases. Centocor is testing Remicade for use by 1.2 million patients in the U.S. with moderate to severe rheumatoid arthritis. Results released in November show that the drug eased pain and joint swelling in patients who found no relief with other treatments. The tests will continue into 1999 to determine whether the benefits can be sustained over a longer period.
Ligand Pharmaceuticals relies on a different technology for Ontak, a drug for treating advanced cases of cutaneous T-cell lymphoma, an disfiguring form of cancer. The company is expecting a decision from the FDA in the next few weeks. The medication is a lab-created protein--a piece of diphtheria toxin fused to Interleukin-2, a natural chemical that seeks out diseased T-cells. In theory, the fused protein acts like a “smart” bomb--killing the lymphoma cells while sparing normal tissue.
Creative BioMolecules and its partner Stryker have completed testing of a surgical paste that stimulates healing in severe bone fractures that would otherwise require a painful graft. The paste contains OP-1, a naturally occurring human protein that Creative BioMolecules discovered a decade ago. It is one of several factors that guide normal bone growth. The product is targeted toward the half a million bone grafts performed every year, said Creative BioMolecules Vice President Steve Basta. The companies hope to win FDA approval in 1999.
Unlike the typical biotech company that creates drugs and other products through genetic engineering, Shaman Pharmaceuticals goes deep into the Amazonian rain forests and consults with native healers in the search for potentially useful prescription drugs. Its most promising compound, currently called Provir, was extracted from the red sap of the Croton tree. The indigenous people in the region brew the stuff into a tea to treat a variety of maladies.
The South San Francisco company has just completed tests of Provir for treating diarrhea in AIDS patients. It said the tests show that Provir works and is well tolerated over a four-week period. The company plans to apply early next year for fast-track approval from the FDA.
Shaman officials believe the drug will fill a need among the country’s 225,000 AIDS patients and the 650,000 individuals who are HIV-positive. Diarrhea is a frequent complication of HIV and the powerful drugs used to treat the virus.
Shaman has also been testing Provir for travelers’ diarrhea and for diarrhea in young children. The company says Americans suffer about 20 million bouts of travelers’ diarrhea annually and that children under 5 experience 35 million episodes of diarrhea each year.
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Times staff writer Paul Jacobs can be reached via e-mail at paul.jacobs@latimes.com.
