Table of Contents
FDA Consumer magazine
May-June 1999
A new biologic treatment has received accelerated approval for treating a rare, slowly progressive form of non-Hodgkins lymphoma.
FDA approved Ontak (denileukin diftitox) Feb. 5 for certain patients with advanced or recurrent cutaneous t-cell lymphoma (CTCL) who have failed to respond to other treatments, such as interferon, chemotherapy or radiation. CTCL causes itchy, dry skin patches that can develop into tumors in the skin and other organs.
Known as "fusion protein," Ontak is made by genetically fusing protein from the diphtheria toxin to interleukin-2 (IL-2), a naturally occurring immune system protein. This stable fusion protein targets and kills cells with receptors for IL-2 on their surfaces, including cancer cells.
Of the 1,000 Americans diagnosed yearly with CTCL, the treatment benefits only the 60 percent or so who have tumors with the IL-2 receptors.
A study of 71 patients with advanced CTCL who had failed at least one other treatment found that in patients receiving Ontak, 30 percent of tumors were reduced 50 percent or more for an average period of four months. Ten percent of patients achieved complete clinical remission for an average period of nine months. Such complete remissions would not be expected in an untreated group.
However, CTCL patients on Ontak need to be monitored carefully during treatment because of the increased risk of severe infection. Their disease makes them prone to infection, as does the treatment because it kills normal lymphocytes along with the cancer cells. Almost one-fourth of the patients in the study developed severe infections, although it was unclear whether Ontak was the cause.
Other side effects related to the intravenous infusion of Ontak included allergic reactions, flu-like symptoms, and fluid retention, which could lead to other complications.
Ligand Pharmaceuticals Inc. of San Diego will market Ontak, which is manufactured by Ligand's subsidiary Seragen Inc., of Hopkinton, Mass.
FDA granted Ontak "orphan" status in 1996, enabling the companies to receive the incentives for developing products for small patient populations. With accelerated approval came a commitment from Seragen to conduct further studies of the drug's long-term safety and efficacy.
(For more on orphan products, see "Orphan Drug Law Matures into Medical Mainstay.")
An improved blood test to confirm the results of other hepatitis C screening tests has received licensing from FDA.
Approved in February, the RIBA HCV 3.0 Strip Immunoblot Assay (SIA) can detect one more type of antibody to the HCV virus than the other licensed supplemental test and is better at distinguishing true positive from false positive results. The older test, while rarely missing a true infection, sometimes falsely signaled the existence of infection. The new test is used when blood specimens test repeatedly positive on other licensed screening tests.
In one clinical trial using healthy blood donors, about 7 percent of repeatedly reactive test results were interpreted as inconclusive using the RIBA 3.0 test, versus about 30 percent when using the previous supplemental test, RIBA HCV 2.0 SIA.
The RIBA 3.0 test has an important role in a recent recommendation by the Department of Health and Human Services that blood banks and medical facilities notify patients who received blood from donors found to be possibly infected with hepatitis C. The new test should prevent thousands of unnecessary notifications and subsequent testing and counseling of blood recipients based on inconclusive tests.
While about 4 million Americans are infected with the hepatitis C virus, making it a major cause of serious injury and death, only 7 percent of cases were acquired from blood transfusions, and most of these infections occurred before 1990, when blood donor screening for hepatitis C became possible. Currently, the risk of contracting the virus from a unit of blood is about 1 in 100,000 units.
The RIBA 3.0 Strip SIA is made by Chiron Corp., Emeryville, Calif., and will be distributed by Ortho Diagnostic Systems Inc., Raritan, N.J.
(For more on hepatitis C, see "Hepatitis C: New Treatment Helps Some, But Cure Remains Elusive" in the March-April 1999 FDA Consumer.)
For those who experience severe pain, aches, or cramping in their legs when they walk due to atherosclerosis, or hardening of the arteries, a new drug treatment is available for the first time in more than 15 years.
FDA approved Pletal (cilostazol) in January to treat pain from intermittent claudication. This condition, affecting several million mostly elderly Americans, results from "peripheral arteriosclerotic vascular disease," when fatty deposits build up in the legs and interfere with the blood supply to leg muscles. It can cause considerable discomfort when walking and seriously interfere with people's ability to exercise and even participate in ordinary daily activities.
Pletal has not been evaluated for safety or effectiveness in patients with more severe peripheral vascular disease, who have claudication pain when they are resting, or who have leg ulcers or gangrene. Such studies are planned.
In clinical trials, patients treated with Pletal were able to walk farther than those treated with a placebo before claudication began and before their pain became intolerable and forced them to stop. Patients treated with Pletal also reported a greater increase than those on a placebo in walking distance and speed during daily routines.
Clinical studies of Pletal did not identify serious toxicity. However, because the drug is related to phosphodiestrase III inhibitor drugs, which have been shown in several studies to increase death rates in patients with severe heart failure, Pletal's labeling states that it should not be used in patients with heart failure. The labeling also states that there is not enough information to determine whether Pletal may negatively affect survival in patients without heart failure.
Additionally, Pletal's labeling informs doctors that information is lacking on combining Pletal with the drug Plavix (clopidogril), recently approved for reducing serious adverse reactions in some patients with peripheral vascular disease. Both Pletal and Plavix inhibit platelet function, raising concerns that their combined use could lead to excessive bleeding. There was no apparent increase in bleeding, though, when Pletal was used with aspirin, which also inhibits platelet function. Further study of the Pletal/Plavix combination will be conducted after Pletal is marketed.
Pletal is marketed by Otsuka American Pharmaceutical Inc., Rockville, Md.
To help consumers use nonprescription, or over-the-counter, drugs properly and understand the benefits and risks of these medicines, FDA is requiring that all OTC drugs have a new, easy-to-read label.
Patterned after the Nutrition Facts label for food, the new "Drug Facts" label must be written in plain language and identify active ingredients first, followed by uses, warnings and directions. It also must include inactive ingredients to help consumers avoid potential allergic reactions.
FDA also recommends that drug manufacturers include a phone number for consumers to call for more information.
The agency developed the new label format in cooperation with consumer and industry groups and after considering almost 2,000 comments on its February 1997 proposed rule. The new drug labels should appear on shelves in the next two to six years.
FDA has received reports of at least 55 adverse reactions, including 19 cases of unconsciousness or coma and one death, associated with dietary supplements containing the chemical GBL (gamma butyrolactone). The agency warns that consumers should not buy or consume GBL products and should throw out any such substances they have on hand.
Other reported reactions include seizures, vomiting, slow breathing, and slow heart rate. At least five children have experienced these kinds of effects.
The agency has asked the manufacturers of the products to recall them voluntarily. If they do not, FDA said it would consider all potential regulatory actions. Though the products are labeled as dietary supplements, FDA considers them illegally marketed unapproved drugs.
In the body, GBL converts to GHB (gamma hydroxybutyrate), a potent experimental drug that is being studied for the sleeping disorder narcolepsy. GHB is legally available only as part of these FDA-approved studies.
The GBL products are being sold on the Internet, in some health food stores, and in some gymnasiums and fitness centers for building muscle, improving physical performance, enhancing sex, reducing stress, and inducing sleep. They are sold in liquid or powder form under a variety of brand names, including Renewtrient, Revivarant or Revivarant G, Blue Nitro or Blue Nitro Vitality, GH Revitalizer, Gamma G, and Remforce. The chemical itself goes by several names, such as 2(3H)-furanone, 2(3H)-furanone dihydro, dihydro-2(3H)-furanone, dihydro, tetrahydro-2-furanone, gamma-butyrolactone, butyrolactone gamma, 4-butyrolactone, butyrolactone, and 4-butanolide.
FDA advises consumers who use these products and develop adverse reactions to contact a doctor immediately. Also, doctors and consumers are encouraged to report adverse reactions to FDA's MedWatch program at 1-800-332-1088 or on the Internet at www.fda.gov/medwatch/.
Milk from cows treated with recombinant bovine somatotropin (rbST) is safe to drink, FDA said in February, affirming the agency's original 1993 conclusions about the growth hormone.
Canadian health officials raised concerns about the safety of rbST, which is used to increase milk production in dairy cattle, while considering whether to approve the product in that country. In response to those concerns and questions raised by several groups and individuals in the United States, FDA's Center for Veterinary Medicine reexamined the human food safety sections of the original approval.
The "Report on the Food and Drug Administration's Review of the Safety of Recombinant Bovine Somatotropin" is available at www.fda.gov/cvm/fda/infores/other/RBRPTFNL.htm on FDA's Website.
Risky raw shellfish ... Seafood lovers may find raw shellfish irresistible, but a recent report by the national Centers for Disease Control and Prevention says that Vibrio parahaemolyticus, a natural marine inhabitant found in shellfish harvested in New York waters, can inflict nausea and diarrhea on unwary diners. CDC says the bacteria isn't as dangerous as its counterpart, Vibrio vulnificus, which is linked to Gulf shellfish and can kill people with liver disease or weakened immune systems. CDC urges consumers not to eat raw or undercooked oysters or clams and to see a doctor and get a lab culture if they become ill within four days of eating raw shellfish.
One out of every two men and one out of every three women aged 40 and under will develop coronary heart disease (CHD) in their lifetime, according to National Institutes of Health researchers involved in the Framingham Heart Study. In their first estimate of this risk, published in the Jan. 9 issue of the journal The Lancet, researchers found the risk of CHD still high at age 70: One out of three men and one out of four women will develop it in their remaining years. Women are frequently not aware of the extent of their heart disease risk--see chart.
Coronary heart disease is the most common form of heart disease, affecting 12 million to 13 million Americans. It occurs when the coronary arteries become narrowed or clogged and cannot supply enough oxygen-rich blood to the heart. CHD can lead to angina (chest pain) and heart attacks.
NIH scientists also reported, in the Jan. 7 issue of the New England Journal of Medicine, that an ultrasound test can predict heart attack or stroke risk in older people who have no symptoms of cardiovascular disease. The noninvasive test uses sound waves to measure the thickness of the walls of two neck arteries, providing information beyond what is available from standard risk factors such as high blood pressure and elevated cholesterol levels.
Stroke "window" widened ... Researchers have shown that for the first time they can reverse massive strokes up to six hours after the onset of symptoms by squirting a new clot-dissolving medicine directly into the brain. In a study by the Cleveland Clinic Foundation, the new approach showed that the previous three-hour deadline for stroke victims to get help before permanent brain damage can set in has doubled. About 600,000 strokes are treated yearly in the United States. (For more information about strokes, see "New Success Against Stroke" in the March-April 1998 FDA Consumer.)
Hope for arthritis sufferers ... Researchers at Brigham and Women's Hospital in Boston report significant improvements in patients with rheumatoid arthritis when the standard treatment medication, methotrexate, was combined with Enbrel, a new genetically engineered drug. The study showed that pain and swelling decreased noticeably in 71 percent of patients who took both drugs for six weeks. Rheumatoid arthritis affects 2 million Americans, mostly women, and usually develops between ages 25 and 50. (New England Journal of Medicine, January 1999)
A guideline on animal drug approval for minor uses and minor species was finalized by FDA in February.
Minor species are defined as any animals other than cattle, swine, chickens, turkeys, horses, dogs, and cats, and sometimes sheep. A minor animal drug use is use in a minor species or use in any animal species for a condition that is rare or that occurs in limited geographic areas.
The document, "Guidance for Industry--FDA Approval of Animal Drugs for Minor Uses and Minor Species," is intended to alleviate the scarcity of safe and effective drugs for these animals. It is available at www.fda.gov/cvm/fda/infores/updates/NEWMUM.html on FDA's Website.
(For more on minor uses and minor species, see "Sick Call of the Wild" in the July-August 1998 FDA Consumer.)
Salmonella detection ... The U.S. Department of Agriculture has developed a technique to rapidly detect a potentially deadly strain of Salmonella known as DT104. Scientists discovered the strain's gene sequence, allowing them to quickly identify the bacterium. DT104 is especially dangerous because it resists many antibiotics. Salmonella is linked to about 3.8 million illnesses annually in the United States and was the second most-common bacterium found in food poisoning cases in 1997.
Staph increases resistance ... A major cause of sometimes fatal hospital infections, Staphylococcus aureus, is developing resistance to the last antibiotic now used to kill it completely, says a study by the national Centers for Disease Control and Prevention. The virulent bacterium is already shrugging off other antibiotics and is one step closer to resisting the antibiotic vancomycin. The findings suggest that hospitals should aggressively contain the bacterium with a combination of antibiotics. (New England Journal of Medicine, February 1999)
Berry good juice ... Drinking cranberry juice has been touted for years as a way to prevent urinary tract infections. Because of the highly acidic nature of cranberries, many have felt that this discourages or even kills bacteria. But a recent Rutgers University study suggests instead that specific tannin compounds in cranberries may prevent Escherichia coli from adhering to the lining of the urinary tract, allowing urine to flush bacteria from the bladder. (New England Journal of Medicine, October 1998)
Genetic link to Parkinson's questioned ... Genetic factors do not appear to play a major role in causing Parkinson's disease in patients over 50 years old, says a study by the Parkinson's Institute in Sunnyvale, Calif. However, a genetic cause is most common in about 10 percent of people diagnosed with the disease before age 50. Of more than 19,000 male twins over 50 tested, Parkinson's disease was most commonly caused by environmental factors, possibly including exposure to chemicals, diet, and smoking. At least 1 million Americans have Parkinson's disease, making it second only to Alzheimer's disease as a degenerative condition of the brain and nerves (Journal of the American Medical Association, January 1999). For more information about Parkinson's disease, see "Parkinson's Disease: New Treatments Slow Onslaught of Symptoms" in the July-August 1998 issue of FDA Consumer.
Growing strains ... Giving growth hormones to short but otherwise healthy children adds only an average of 2 inches to their adult height, a Stanford University study found. Experts now question whether long-term hormone therapy in these children is worthwhile. The study was based on the height patients were predicted to attain before treatment, and it compared their subsequent growth to children who weren't treated. (New England Journal of Medicine, February 1999)
Smoking and weight loss ... Contrary to popular belief, smoking does not keep people from gaining weight, says a seven-year study by the University of Memphis. In fact, the research showed that weight gain of more than a pound a year was common whether subjects smoked or not. (Journal of Consulting and Clinical Psychology, December 1998)
Correction: The January-February issue of FDA Consumer contained an incorrect statement about the drug Arava (leflunomide) for rheumatoid arthritis. While other oral treatments are available for the disease, Arava is the first oral treatment approved for slowing its progression.
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