Directory of Drugs Therapeutic Area Updates
Nephrology/Urology
The National Kidney Foundation estimates that about 20 million Americans are affected by kidney and urological diseases. For a number of reasons, kidney disease is one of the costliest diseases. End stage renal disease, necessitating transplantation or chronic hemodialysis, is extremely costly.
Chronic renal insufficiency increases the likelihood of adverse drug events in the ambulatory setting as well as in hospitalized subjects. The elderly population is already at risk for adverse drug reactions because they tend to be on multiple medications. For those patients with renal insufficiency, the increased risk for adverse drug reactions is multiplied exponentially. Thus, health care costs are increased in subjects with decreased renal function.
Urological diseases and diseases affecting the kidney are prevalent. For example, benign prostatic hypertrophy (BPH) can is found histologically in more than half of men over age 60 and in almost all men over age 85. Diabetes and hypertension, which adversely affect renal function over time, are found in seven million Americans and 23% of subjects ages 20-74,
Kidney disease is responsible for 50,000 deaths each year. The economic
cost of kidney and urological disease in this country is $26.3 billion;
more than two third of this cost is due to end stage renal disease. Some
statistics relevant to urological and nephrological conditions are as
follows:
|
Condition |
Prevalence |
|
Benign Prostatic hypertrophy |
- 50% of men over age 60 years |
|
Erectile dysfunction |
10-30 million men |
|
End stage renal disease (ESRD) |
260,000 subjects each year |
|
Kidney stones |
500,000 subjects each year |
|
Urinary Tract infections |
8 million physician visits/year |
|
Interstitial cystitis |
About 700,000 subjects |
|
Polycystic Kidney Disease (PKD) |
600,000 subjects |
|
Kidney/urological disease (general) |
- 6 million hospitalizations each year |
There are currently more than 40 drugs in clinical trials for kidney and urological conditions. Interestingly, there seem to be few clinical trials in the field of benign prostatic hypertrophy even though this condition affects a sizeable proportion of the general population. CenterWatch has identified four ongoing clinical trials for drugs related to BPH. Medical management of BPH with alpha-receptor blockers has been found to be effective so clinical trials are focusing on the use of highly selective drugs in this category. The three drugs undergoing trials are Alfuzosin, S-doxazosin and Ml-04. Alfuzosin is approved for use in many non-US countries; in October 2001, Sanofi-Synthelabo reported that it had received a FDA approvable letter for UroXatral, the once-a-day formulation of Alfuzosin. S-doxazosin is the single-isomer version of Cardura, a currently available alpha-receptor blocker approved for the management of BPH and hypertension. S-doxazosin has the potential to significantly reduce the side effect of orthostatic hypotension that is experienced with Cardura.
Other pharmacologic treatments for BPH involve the use of inhibitors of the 5-alpha-reductase enzymes. These enzymes are responsible for the conversion of testosterone to dihydrotestosterone (DHT) in prostatic tissue. DHT, not testosterone, is primarily responsible to prostatic hypertrophy. Inhibitors of this enzyme should affect prostate size and have been shown to reduce prostate size by 20% to30%. Finasteride, a currently widely used drug for the medical management of BPH, has been found to reduce the incidence of urinary retention and prostate surgery over time. The FDA approved another drug in this class: Dutasteride, a dual-inhibitor of the 5-alpha-reductase enzyme.
A major focus is erectile dysfunction with currently more than 15 clinical trials for this indication. The introduction of Viagra has moved the estimated cost of management for this condition from $800 million to billions of dollars. There are two drugs similar to Viagra that are currently under review by the FDA; Tadalafil and Vardenafil are also phosphodiesterase type 5 inhibitors that have shown effectiveness in clinical trials for the management of erectile dysfunction.
At least 10 drugs are in clinical trials for the prevention and management of patients with end stage renal disease. One potentially exciting development is in the phase I trials, AVI-4126. This is a third-generation antisense drug that specifically targets and inhibits c-myc, a gene believed to be critical in PKD. Unrestrained cell growth caused by growth factors produced by this gene is thought to be responsible for the cystic changes that characterize the kidneys of PKD subjects.
A recent approval in the area of end stage renal disease is Darbepoetin (Aranesp), a long-acting formulation of erythropoietin. Currently, erythropoietin has to be given as multiple injections every week. Aranesp has the advantage of being given once every three weeks.
Two other therapies undergoing evaluation in clinical trials deserve
mention. The first is Gemifloxacin, a broad-spectrum fluoroquinolone,
that is being developed for the treatment of various bacterial infections.
An NDA has been submitted for the management of urinary tract infections.
The second is a vaccine being developed to prevent urinary tract infections
in women. MedImmune has conducted phase I trials for this vaccine; results
have demonstrated a clear dose response with volunteers developing serum
antibodies in urine and vaginal secretions. These antibodies seemed
to be effective in preventing bacteria from binding to human bladder
cells. With the high prevalence of urinary tract infections in both
men and women, this vaccine can have tremendous impact on the health
of the general population and the costs of treatment for this condition.
