Cw1001_jan02.qxd

Grant Opportunities
Eye On: Sexual Dysfunction
In both men and women,sexual dysfunc- For psychosocial causes of female SD, cessful penetration in 91% of subsequent
tion (SD) may result from physical or psy- education and counseling may be effective.
thorough evaluation. Often it is underreport- levels of estrogen and testosterone affected by phase III clinical trial of 440 men showed that ed because of reluctance by both patients and age, surgery or endocrine dysfunction, but is Levitra was equally effective in ED related to physicians to discuss sexual issues.
often ineffective, and hormonal interactions Nonetheless, SD affects between 10% to 52% often lead to unpredictable outcomes. Viagra is currently being tested in women, and it including headaches, flushing and rhinitis.
Erectile dysfunction (ED), or inability to may restore libido in women using antide- Unlike Viagra, Levitra was not associated obtain and/or maintain penile erection suf- with visual symptoms such as the perception ficient for vaginal penetration and satisfac- tory intercourse, affects 10 million to 30 mil- that improve libido, sexual performance and Because of Cialis’ long duration of action, lion men in the U.S., and 75 million to 100 sexual response in both sexes. CenterWatch million men worldwide. Incidence increases has identified a pipeline of 30 drugs in vari- additional safety testing, and may be con- ous phases of clinical development for SD.
cerned about its potential for recreational use These drugs act on different neuroendocrine pathways and are available in a variety of sys- trolled trial in 1,112 men, Cialis was consis- formance anxiety, stress, depression and mar- tently safe and effective across disease severi- ital conflict; while organic causes include vas- ties and etiologies, as well as in patients of all cular disease, diabetes mellitus, hypertension, Cialis (tadalafil) are orally administered ages. Headache and dyspepsia were the most use of certain medications, multiple sclerosis phosphodiesterase type 5 (PDE5) inhibitors, and other neurologic disorders, alcoholism, which magnify the natural erectile response Lilly ICOS is also in phase II testing of heavy smoking, pelvic trauma and prostate Cialis for female sexual dysfunction.
muscle cells in the penile vasculature and increasing penile blood flow. Onset of action penile blood flow is Invicorp, a self-injection is about one hour for Viagra, 30 minutes for implants, are typically cumbersome, embar- Cialis, and 30 to 40 minutes for Levitra.
mesylate and vasoactive intestinal peptide rassing or uncomfortable. Testosterone and Duration of action is four hours, three days, (VIP), a 28-amino-acid peptide found natu- other hormone injections are indicated only rally in the urogenital tracts of both sexes.VIP in patients with documented low testosterone Bayer has received an FDA approvable let- causes erection by binding to smooth muscle levels, and are generally ineffective, with occa- ter and expects to launch Levitra in Europe in receptors in the corpus cavernosum, inducing the first half of 2003. Levitra contains a more efficient PDE5 inhibitor than do Viagra and Cialis, making it more potent. On April 30, approved for marketing in the U.S. But, up to 2002, Lilly ICOS received an FDA approvable one-third of men find no improvement with letter for Cialis, which was approved by the approved in several European countries. In Viagra. Fears of cardiac adverse events and European Commission in November 2002.
completed phase III clinical trials in Europe interaction with nitroglycerin also prevent In a 26-week phase III trial of Levitra in effective overall. The most common side effect In women, SD includes disorders of libido, persistent improvement in erectile function.
was transient facial flushing. Advantages arousal and orgasm, as well as dyspareunia include no known contraindications, onset of and vaginismus. Chronic medical or gynecol- Levitra were able to have intercourse on their erection within two to five minutes, duration ogical diseases, medication use and psychoso- first attempt, compared with 45% of those of action up to 2 1/2 hours after administration, cial difficulties, including prior physical or taking placebo. Those men who were success- natural termination of an erection after ejacu- ful the first time continued to achieve suc- Industry Reports
Sexual Dysfunction
Corporation is Topiglan, a topical gel formu- phase II testing of an intranasal spray formu- lation, and efficacy in the treatment of organ- lation of apomorphine, which is being tested ic ED. It uses a novel drug delivery system with prostaglandin E-1. In earlier studies, Topiglan pre-filled drug delivery cartridges.
Late last year, the FDA placed a temporary achieving erection, or 40% response rates in transdermal testosterone, including a patch in hold on all clinical trials involving phento- lamine mesylate because of carcinogenicity in response rate to placebo gel. As expected from Pharmaceuticals; Tostrelle gel in phase II/III its first-pass metabolism, systemic effects claims this has no relevance in humans.
were minimal, allowing safe use in men with LibiGel, in phase II development by BioSante cardiovascular disease. Trials are now on clin- ical hold because phase III testing showed a positive trend but not statistical significance tion may not change significantly with testos- lamine mesylate which blocks alpha recep- in the ability to maintain erection to comple- terone, although subscales for sexual pleasure tors. A 1998 study showed that Vasomax was and orgasm show selective improvement.
effective in 25% to 40% of men with ED, with required for approval of an ED drug.
Transdermal testosterone delivery does not onset of action within 20 to 30 minutes.
Topical alprostadil may also be useful in appear to alter estrogen levels, interfere with hormone replacement therapy, increase acne phentolamine product for female SD. Phase II increasing genital blood flow. Vivus is in phase or hirsutism, or change blood lipid levels.
testing was completed in Mexico for this vagi- IIb testing of Alista, while NexMed is in phase nal suppository, which improves clitoral and II development of Femprox, which utilizes the vaginal blood flow, lubrication and sensation.
NexACT platform drug delivery technology.
breast cancer, heart disease and hepatocellu- NDA application for Alibra in ED, but is now peripherally to stimulate genital blood flow, administered hormones such as Estratest, an receptor agonist working centrally in the estrogen/methyltestosterone formulation for prazosin HCl is a urethral microsuppository brain and spinal cord to stimulate release of which Solvay Pharmaceuticals has completed designed to deliver effective drug levels to dopamine. This neurotransmitter is involved erectile tissues while limiting systemic expo- in pleasure sensations and in the erection sure and potential for adverse effects.
response. TAP Pharmaceuticals has submit- had its share of setbacks. Furthest along the Alprostadil is a vasodilator, which increases ted an NDA for Uprima, a novel sublingual penile blood flow, and prazosin is an adrener- Viagra, which may be partially limited by gic receptor antagonist. In clinical trials In phase II/III clinical trials in 5,000 men, unwanted cardiovascular and other systemic involving more than 1,000 men at 44 U.S.
an Uprima dose of 2-3 mg offered the most sites, Alibra has been safe and effective within favorable risk/benefit ratio. The proportion 5 to 10 minutes of application, with a dura- approval due to safety concerns. Hormonal enough for intercourse was 49.4% with 3 mg, manipulation or use of central agonists such compared with the baseline value of 24.3%.
as apomorphine are alternative approaches NexMed, is a topical preparation containing which offer promise, as of yet unfulfilled. In alprostadil for transdermal delivery. In two within 10 minutes, and 71% within 20 min- an area such as SD where the placebo effect is randomized, parallel, double-blind, placebo- utes. Adverse reactions included headache in considerable, demonstration of efficacy is controlled, phase II studies in the U.S., up to 7%, nausea in 7%, dizziness in 4%, and vaso- another obstacle to approval of many drugs 83% of 300 subjects reported satisfaction vagal syncope in less than 0.2%. Despite its with treatment. Most side effects were tran- sient and only mild to moderate in severity.

Source: http://rc.kfshrc.edu.sa/ORA/grants/CenterWatch/Eye%20On%20Sexual%20Dysfunction.pdf