Food and Drug Administration
U.S. Department of Health and Human Services
Public Health Service 5600 Fishers Lane Rockville, MD 20857
FDA Talk Papers are prepared by the Press Office to guide FDA personnel in responding with consistency and accuracy to questions from the public on subjects of current interest. Talk Papers are subject to change as more information becomes available.
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January 18, 2000
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Groups benfiting from the more than 140 advanced medications and medical devices that had been approved after meeting FDA's exacting standards include people with cancer, HIV, diabetes, neurologic diseases and poor vision as well as many patients suffering from rare diseases.
These new additions to the health care armamentarium include a new class of drugs for the treatment of osteporosis in post-menopausal women as well as state-of-the-art equipment that uses a laser to create tiny holes in heart muscles that cannot be treated by an artery bypass; two new members of a family of drugs for diabetes; two new biological agents for bleeding disorders; and several new combination devices for blood testing and separation.
In 1999, FDA's medical product centers, the Center for Drug Evaluation and Research (CDER), Center for Biologics Evaluation and Research (CBER) and Center for Devices and Radiological Health (CDRH) continued to demonstrate strong scientific expertise and increased efficiency. The results have benefited patients in the United States while providing the pharmaceutical industry with a predictable timetable for prompt regulatory decisions.
Two studies released last year document the benefits of FDA's review and approvals and indicate that Americans have an increasingly fast access to new medications of world-wide origin.
One of the studies (Tufts Center for Study of Drug Development, July 1999) showed that since the passage of the Prescription Drug User Fee Act of 1992, total development time for new drugs in the U.S. has dropped by 18%. Another study (Ashton CMRI International News, Spring 1999, Vol 17, No. 1) found that in 1998, about 75% of world-wide new molecular entities were first launched in the U.S.
Listed below are some of the groups of patients with diseases for which FDA approved products last year:
Patients with rare diseases: One of the largest groups of products approved last year is for the treatment of rare diseases with patient populations too small to make the development of such drugs and devices routinely profitable.
FDA approves these products under two programs. One is the 16 year-old Orphan Drug program which grants special privileges and marketing incentives for drugs and biologics for the treatment of conditions affecting fewer than 200,000 Americans.
The other program, called the Humanitarian Device Exemption (HDE), was authorized by the Safe Medical Devices Act of 1990. HDE exempts the manufacturer from conducting clinical trials to prove the effectiveness of products that have been shown to be reasonably safe and present a probable benefit for a U.S. patient population of fewer than 4,000.
In 1999, FDA approved 20 new Orphan drugs and biologics and seven HED devices. Several of these products offered new hope for patients with rare forms of cancer, including patients who have advanced or recurrent cutaneous t-cell lymphoma (CTCL), a slow-growing form of non-Hodgkin's lymphoma, and who have not been helped by other treatments. Each year, some 1,000 people in the U.S. are diagnosed with CTCL, often a slowly progressive disease causing dry skin patches that can develop into tumors in the skin and other organs.
One of the two new treatments for CTCL is denileukin diftitox (Ontak), a biological agent produced by genetically fusing protein from the diphtheria toxin to interleukin-2 (IL-2), a naturally occurring immune system protein. This protein targets malignant and normal cells with receptors for IL-2, resulting in cell death.
The other new orphan product for CTCL is bexarotene (Targretin), a member of the retinoid class of drugs that is associated with birth defects in humans and must not be administered to pregnant women.
Another FDA high priority approval was for epirubicin hydrochloride injection (Ellence), to treat early stage breast cancer that has spread to the lymph nodes under the arm and has been treated surgically with removal of all known tumor.
Epirubicin is commonly used in combination with other medications to slow or halt the progression of cancer.
Adult patients who have anaplastic astrocytoma, a rare form of brain cancer, and who have relapsed after chemotherapy that included carmustine or lomustine and procarbazine, can now be treated with temozolomide (Temodar), one of the most important new Orphan drugs approved last year.
Approximately 18,000 new cases of primary brain cancer are diagnosed each year in the U.S., representing about two percent of all adult cancers. About half of these patients have brain tumors and suffer severe disabilities such as motor dysfunction, seizures and vision abnormalities.
Last year's approvals included two new orphan drugs for people with bleeding disorders. A plasma-derived antihemophilic factor/von Willebrand factor complex (Humate-P) was approved to treat severe cases of von Willebrand's disease, an inherited ailment that results in excessive bleeding following an injury or heavy menstrual flow.
FDA also gave orphan drug approval to recombinant coagulation factor VIIa (NovoSeven) which can be used to treat bleeding episodes in hemophilia A or B with antibodies to coagulation factors VIII or IX.
Infants and children with rare diseases could benefit from several new products approved under the orphan drug program and HDE.
Somatropin (Nutropin Depot), a genetically engineered drug, was approved for long-term treatment of growth failure, and etanercept (Enbrel) was approved for the treatment of polyarticular course juvenile rheumatoid arthritis.
Caffeine citrate (Cafcit) is a short-term pediatric treatment for apnea (breathing interruptions), and poractant alfa (Curosurf) can be used for relief from the respiratory distress syndrome. Another new product for respiratory failure in term or near-term infants is nitric oxide (INOmax).
In addition, FDA granted a humanitarian device exemption to The Shelhigh Pulmonic Valve Conduit NR-4000 to be used in replacing diseased, damaged or absent pulmonic arteries in small children or infants with certain cardiac conditions.
Another HDE approval, the Cardioseal Septal Occlusion Systems, uses a transvascular method for closing holes between the left and right sides of the heart in a selected population of patients with complex ventricular septal defects.
People with Cancer. Women with breast cancer (185,000 are diagnosed each year) are one of the largest groups among the eight million Americans with cancer, the second deadliest disease in the U.S. Breast cancer kills 46,000 women a year.
In addition to epirubicin (Ellence), which was approved under FDA's Orphan Drugs program, FDA last year approved exemestane (Aromasin) for advanced breast cancer in postmenopausal women whose disease has progressed following tamoxifen therapy.
FDA also approved the T-Scan, a new imaging device that can help radiologists determine whether a woman should be evaluated further when the results of her mammogramms are ambiguous. The sophisticated equipment can facilitate an early discovery of breast cancer, when it is more readily treatable.
FDA's approvals also included new oncologic indications for several drugs already on the market. One of them is docetaxel (Taxotere), which was originally designed for treating patients with advanced breast cancer, and now is approved for use in non-small cell lung cancer that does not respond to chemotherapy.
In addition, FDA approved two products that can help prevent cancer by treating conditions that frequently precede the onset of the disease.
One of these products is celecoxib (Celebrex), a non-steroidal anti-inflammatory drug which was last year granted an accelerated approval as a product that promised therapeutic benefit for a life-threatening condition that has no other acceptable treatment.
Celecoxib is the first drug treatment (together with endoscopic surveillance or surgery) for familial adenomatous polyposis (FAP), a genetic disorder. The new indication is for the reduction in the number of adenomaous colorectal polyps in FAP, which greatly increase the risk of developing colon and rectal cancer in young patients.
The other potentially cancer-preventing product is aminolevulinic acid HCl (Levulan Kerastick), the first drug/device for the treatment of precancerous skin lesions on the face and scalp.
Patients with HIV and AIDS. FDA's work in 1999 added several new products to the growing number of treatments for patients with HIV virus and AIDS.
One of them is amprenavir (Agenerase), a new protease inhibitor that received an accelerated approval for use in children as young as four and in adults in combination with other antiretrovirals for HIV infection. Amprenavir is one of five FDA-approved protease inhibitors that attempt to prevent HIV from making new copies of itself by interfering with the HIV protease enzyme.
The other new HIV product is alitretinoin (Panretin), a topical gel for the treatment of cutaneous lesions in patients with AIDS-related Kaposi's sarcoma.
In addition, Videx Chewable Tablets and Oral Solution were approved in a new strength (200 mg) that allows a change in dosing interval to once-daily when used in combination therapy for HIV infection.
The Elderly. Approved new medications and indications added to the treatment options for many of the 18 million Americans -- mostly senior citizens -- affected with rheumatoid arthritis and osteoarthritis.
Rofecoxib (Vioxx), a new drug for treatment of ostearthritis, menstrual pain and the management of acute pain in adults, is a type of non-steroidal anti-inflammatory drug (NSAID) known as "Cox-2 inhibitor."
NSAID products temporarily relieve pain by blocking the body's production of prostaglandins, the chemicals believed to be associated with the pain and inflammation of injuries and immune reactions. NSAIDs, which inhibit an enzyme called cyclo-oxygenase-2 (Cox-2), are expected to have a lower incidence of such side effects as gastrointestinal ulcers and bleeding.
In addition, FDA approved a new indication for rheumatoid arthritis for infliximab (Remicade), a biological agent that had been previously approved for the treatment of certain patients with moderate to severe Crohn's disease.
The agency also approved a combination of aspirin and extended-release dipyridamole (Aggrenox) for the reduction of the risk of stroke in patients who have had transient ischemia of the brain or completed clotting stroke due to thrombosis.
Stroke affects about 500,000 people in the U.S. each year, with approximately 150,000 dying as a result. Four-fifths of these strokes are ischemic; the rest are caused by bleeding into and around the brain.
People with Diabetes. Three new products approved last year will bring benefits to many of the 16 million Americans affected by diabetes, a disease that can cause damage to the eyes, kidneys, heart and peripheral circulation.
Patients with the highly prevalent type II or adult-onset diabetes who are not adequately controlled by diet and exercise alone can be treated with pioglitazone (Actos). Pioglitazone is one of two new drugs in the thiazolidinedione class that can improve patients' ability to utilize insulin, believed to be the main underlying cause of adult onset of diabetes.
The other new approved product in this class of drugs and for the same population of patients -- which includes 90% of all people with diabetes in the U.S. -- is rosiglitazone (Avandia).
In addition, FDA has approved a new device that provides physicians with continuous measures of tissue glucose levels in adults.
The Continuous Glucose Monitoring System is the first diabetes device that uses a sensor inserted under the patient's skin and is connected to a small external monitor. The device records tissue glucose levels at five-minute intervals for up to three days. The information is than downloaded on a computer for review by health care professionals.
People with Hepatitis. About four million people in the U.S. have chronic hepatitis C, the nation's most common blood-borne infection that poses a serious risk of cirrhosis, liver cancer and liver failure, and can lead to liver transplantation.
FDA's approvals last year for the treatment of hepatitis C included a new biologic, interferon alfa-n1 (Wellferon), for patients age 18 or older; an expanded indication for interferon alfacon-1 (Infergen); and a new dosage regimen for interferon alfa-2 (Referon A).
The agency also approved a new indication for hepatitis B vaccine (Recombivax). The new version of this vaccine does not contain a preservative.
In addition, FDA approved two tests for this infection. One of them is The Hepatitis C Check, the first home test that does not require a prescription. It is used to collect a sample of blood which is then mailed to a laboratory for testing for antibodies to the hepatitis C virus.
The other test is Riba HCV 3.0 Strip Immunoblot Assay (SIA), an improved and more specific version of a previous supplemental blood banking test that can detect one more type of antibody to the HCV virus and is better at distinguishing truly positive from falsely positive test results.
Cardiac Patients. Thousands of Americans with heart disease suffer disabling chest pains that cannot be adequately controlled by medications or balloon angioplasty. Many of these patients will benefit from several state-of-the-art devices approved last year.
One of them is AngioJet, which was reviewed in less than six months as a possible alternative treatment for patients who cannot use so-called clot-busting drugs. This device is a coronary catheter system for extracting blood clots from blocked heart arteries or bypass grafts prior to angioplasty.
Other new approved devices include the Eclipse TMR Holmium Laser System, for puncturing tiny holes in the heart muscle in areas inaccessible to treatment by coronary artery bypass; and Ensite 3000 and Tracer 02T-W Mapping Device, for diagnosing complex atrial arrhythmias so that appropriate treatment can be planned.
Other significant approvals. Other notable approvals in 1999 included two psychopharmacological treatments which are first of their kind.
They are paroxetine HCl (Paxil), the first drug for people with social phobia, and sertraline hydrochloride (Zoloft) the first drug for posttraumatic stress disorder, which has long been recognized as an important clinical problem.
The armamentarium against infectious diseases was strengthened with three important new products.
One of them is quinupristin and dalfopristin injection (Synercid), the first antibacterial drug to treat infections caused by vancomycin-resistant Enterococcus faecium, a bacterium that has become highly resistant to older antibiotics. This drug was also approved for complicated skin and skin structure infections.
The other two are new antiviral therapies for treatment of people infected with the virus that causes influenza. The new products are zanamivir (Relenza), an inhaled drug for adults and adolescents who are 12 or older, and oseltamivir phosphate (Tamiflu), a capsule indicated for onset of influenza A and B.
Nearsighted people can be helped with two devices approved last year: KeraVision Intacs, tiny acrylic crescents that can be implanted into the eye to correct mild myopia; and SVS Apex Plus Excimer Laser Workstation, an eye laser for use in correcting myopia with or without astigmatism in adults.
A major pediatric approval was Immune Globulin Intravenous for treatment of the Kawasaki syndrome, a painful disease which is characterized by high fever and occurs primarily in children under five years of age.
Other significant approvals last year included Sirolimus (Rapamune), a new immunosuppressant drug, to be taken together with cyclosporine and corticosteroids to prevent acute organ rejection in patients receiving kidney transplants; levetiracetam (Keppra), a new epilepsy drug that helps control partial onset seizures in adults; and orlistat (Xenical), a new lipase inhibitor to treat obesity.
FDA also approved several new diagnostic tests. One of them is Binax, a simple, quick, first-of-a-kind urine test for detecting Streptococcus pneumoniae, one of the bacteria that is a leading cause of pneumonia.
The other important new test is for Lyme disease. The PreVue B. burgdorferi Antibody Detection Assay can be used in a doctor's office and provides results in an hour at the point of care, thus making possible a prompt treatment with antibiotics.
FDA's Performance. The products discussed in this report represent only a small part of CDER's, CBER's and CDRH's performance. Both CDER and CBER met or exceeded practically all of the review performance goals of the Prescription Drug User Fee Act of 1992, which was reauthorized in 1997. Not all of these reviews, however, resulted in approvals because some submissions were not approved and others had to be returned to the sponsors for additional information.
Each of the products approved during 1999 offer meaningful public health benefits. Like all medical interventions, the use of approved medical products involves certain risks that the agency seeks to reduce by accurate and complete labeling, by restricting the products' use and by requiring special warnings for patients about potentially serious side effects.
Even after a medical product reaches the market, FDA remains alert to the appearance of new risks, and continually assesses adverse events reports to make sure that each product's benefits generally outweigh the known risks when used as directed.
During calendar year 1999, CDER took 190 actions on original new drug applications. Eighty-three actions were drug approvals and occurred in the median total time of 12.0 months. Twenty-eight of these approvals were for priority products considered to be of potentially exceptional public health value. They were approved in the median approval time of 6.1 months. The priority and regular approvals included 35 new molecular entities that had not been previously marketed in the U.S. and were approved in the median approval time of 11.6 months.
In 1999, CBER took 59 actions on license applications for both user fee and non-user fee products, 9 of which were for priority biologics. Twenty-four of the actions were approvals which were completed in the median time of 8.37 months, and they included three approvals for priority products whose median time to completion was 13.8 months. Two license applications did not meet the conditions for filing and 3 were withdrawn. CBER received 39 new product license applications in 1999, 10 more than in the previous year.
CDRH took during last calendar year 296 actions on premarket approval applications (PMAs), which represents the highest level of premarket scrutiny for medical devices. Of these actions, 41 were approvals, including seven for PMAs eligible for Humanitarian Device Exemptions (HDEs). Total reviews of approved PMAs were completed in the median time of 9.1 months. For HDEs, the median total review time was 6.0 months. CDRH also took 4,491 actions on premarket notifications, and cleared for market 3,569 of these products in the median total review time of 2.4 months.