Hundreds of new drugs are in the pipeline that treat women's diseases
It is now commonly accepted that women react differently than men do to drugs. But it took years to recognize this. It has been only since 1993after the Food & Drug Administration issued guidelines for the study of gender differences in the clinical evaluation of drugsthat women have been routinely included in the pharmaceutical assessment of the safety and efficacy of new products.
Only a decade has passed since the FDA opened its Office on Women's Health. And, it was only in 2000 that the FDA issued a rule to halt clinical trials of new drugs to treat life-threatening diseases if the trials excluded women solely because they might become pregnant during the test.
The result of this prejudice was a lack of medical knowledge related to how women react to many medications. "Historically the medical community has focused insufficient resources or attention on gender differences," said Marianne J. Legato, M.D., director of the Partnership for Gender-Specific Medicine at Columbia College of Physicians and Surgeons at Columbia University in New York, N.Y. "It is only recently that original research in women's health has gained notice and has become a separate discipline for medical investigation," she said.
That's true, said Alan Goldhammer, Ph.D., associate VP for regulatory affairs at Pharmaceutical Research & Manufacturers of America. Today, the FDA increasingly finds itself evaluating drug company product applications that address diseases afflicting women in greater numbers or in different ways from men, according to PhRMA surveys.
"Our knowledge of how drugs affect women has grown significantly in the last five years," said Goldhammer. "This is allowing a better understanding of drug safety issues and other FDA concerns. There's more work that needs to be done in collecting data, but a key factor as we move forward is our increasing ability to identify subpopulations at risk for adverse reactions. Our recent surveys show that the FDA is heavily involved in the evaluation of drugs for diseases that predominantly affect women."
PhRMA surveys support that contention. A PhRMA survey published in March 2004 found the FDA currently has 371 medicines in the pipeline for diseases that disproportionately affect women. The medicines are either in human clinical trials or awaiting FDA application review. A 2001 PhRMA survey found similar numbers: At that time, 358 drugs were in the pipeline for diseases that disproportionately affect women.
"In the pipeline doesn't mean all those drugs will make it all the way through," cautioned Goldhammer. "Many need a great deal more research." According to the FDA, it takes 10 to 15 years for an experimental drug to travel from the lab to patients. Only five in 5,000 compounds that enter preclinical testing make it to human testing, and only one of the five medicines tested in people is approved.
Today, a significant part of the money spent on R&D by pharmaceutical companies is spent on drugs that treat diseases predominantly affecting women, said PhRMA officials. Women tend to live five years longer than men and "are more susceptible to a number of diseases," said PhRMA President Alan F. Holmer. "Pharmaceutical companies are zeroing in on those diseases, as well as on heart disease, cancer, and stroke, the three leading killers of both women and men."
Some of the drugs currently in the pipeline mark potentially significant developments. For example, among the potential treatments is an agent for multiple sclerosis (the first in a new class), which is based on a humanized monoclonal antibody, designed to prevent the adhesion of immune cells to blood vessel walls and the migration of inflammatory cells from blood vessels into tissues. Another potential medicine is one for rheumatoid arthritis, using a "trap" technology to stop the growth of the disease. And a third is a new medicine for metastatic breast cancer, designed to bind to and inhibit vascular endothelial growth factor (VEGF), a protein that plays a critical role in the formation of new blood vessels that feed the tumor.
Here is an overview of some of the diseases disproportionately affecting women being targeted for new drug development, according to PhRMA's 2004 Survey of Medicines in Development for Women:
Breast cancer will kill an estimated 39,800 American women this year, and an estimated 211,300 women will be newly diagnosed with the disease, according to PhRMA. There are 71 new drugs in the pipeline for treating cancer, including 41 for breast cancer, 34 for ovarian cancer, and 10 for cervical cancer.
Rheumatoid arthritis (RA) affects 1.5 million American women. A potential "first-in-class" medicine under consideration modulates the autoimmune T-cell function, which helps to stem the cascade of inflammation that leads to joint damage. In clinical trials the new medicine was shown to relieve the signs and symptoms of RA. There are 55 drugs in the pipeline for arthritis/musculoskeletal disorders. Arthritis affects 41 million women, and musculoskeletal disorders cost the economy nearly $125 billion annually in direct expenses, lost wages, and reduced productivity, according to PhRMA.
Alzheimer's disease affects an estimated 4.5 million Americans, two to three times as many women as men, including 50% to 70% of women over the age of 80. A potential medicine for Alzheimer's disease has two mechanisms: It blocks the production of beta amyloid protein, which forms plaques in the brains of Alzheimer's patients, and it inhibits the degradation of the neurotransmitter acetylcholine. A report by researchers at the National Institutes of Health indicates that the medicine might be able to not only improve symptoms of Alzheimer's patients but also impede the progression of the disease, according to PhRMA. There are 21 drugs in the pipeline for Alzheimer's disease.
Multiple sclerosis (MS) is a progressive disease of the central nervous system, affecting twice as many women as men. Estimates of the number of people with MS range from 250,000 to 500,000. One medicine in development for MS is the first in a new class of agents known as alpha-4 integrin inhibitors. It is a humanized monoclonal antibody designed to block the adhesion of immune cells to blood vessel walls and the migration of inflammatory cells from blood vessels into tissues. In clinical trials, patients who took the drug had fewer relapses than patients who took the placebo. There are 13 drugs in the pipeline for the treatment of MS.
Osteoporosis is a major public health threat for an estimated 44 million Americans, 80% of whom are women. In a healthy young person, the rate of bone formation and breakdown is balanced. But in older women, breakdown often occurs at a faster rate than formation, resulting in osteoporosis. Currently approved medicines slow either the breakdown or resorption of bone. Among potential medicines is an injectable version of human parathyroid hormone, a naturally occurring protein that may be able to speed up bone formation. Human parathyroid hormone speeds both the formation and the resorption of bone, with a net increase in bone formation. It is hoped that this drug may be able to reversenot just slowthe course of the disease, according to PhRMA. There are 20 drugs in the pipeline for the treatment of osteoporosis.
Incontinence affects some 13 million Americans, 85% of whom are women. One medicine in development for overactive bladder suppresses bladder contractions by blocking a receptor in the smooth muscle of the bladder. A medicine in development for stress urinary incontinencewhen coughing, sneezing, laughing, or exercise puts pressure on the bladder and causes urine leakageis a balanced dual reuptake inhibitor, which blocks the reuptake of the neurotransmitters serotonin and norepinephrine.
Systemic lupus erythematosus (SLE) or lupus affects more than 200,000 women in the United States, comprising about 90% of all lupus patients. In lupus, the body develops antibodies that react against normal tissue, leading to inflammation, pain, tissue injury, and major organ damage. PhRMA says there has been no new medicine approved specifically for lupus in 40 years. But a medicine now in clinical trials shows promise in reducing renal flares, the kidney-destroying inflammation that is the leading cause of illness and death in lupus patients, according to PhRMA.
Fibromyalgia syndrome is a chronic pain syndrome that affects an estimated four to six million Americans, of whom 80% are women. There are no drugs specifically approved in the United States for the treatment of fibromyalgia syndrome. One medicine in development is the first in a new class of drugs known as norepinephrine serotonin reuptake inhibitors. The medicine decreases the uptake of two key neurotransmitters, norepinephrine and serotonin, which play an essential role in regulating pain and mood, according to PhRMA.
Other medicines in development target psoriasis, scleroderma, cervical cancer, glaucoma, urinary tract infections, chronic bronchitis, migraine, anxiety, irritable bowel syndrome, sepsis, and other diseases. In other surveys, PhRMA found that researchers have 123 medicines in the pipeline for heart disease and strokeconditions that kill half a million women each yearand 70 medicines for lung cancer, the leading cancer killer of American women.
Martin Sipkoff. Hundreds of drugs in the pipeline target conditions in women. Drug Topics May 2, 2004;148:5s.