New ED Drug Green-Lighted for Phase III Trials

By William T. Elliott, MD, FACP

Bayer’s new erectile dysfunction (ED) drug vardenafil is entering phase III trials after European data suggest that it is effective in up to 80% of men regardless of the severity or cause of ED. The data were reported at the annual meeting of the European Association of Urology. The drug is a phosphodiesterase-5 inhibitor like sildenafil (Viagra), but it may be more specific for the enzyme than sildenafil, possibly resulting in fewer side effects. Bayer is projecting the results of this phase III testing by the end of the year, with a 2002 product launch projected.

PPI Update

The FDA has approved the first intravenous proton pump inhibitor (PPI). Wyeth’s pantoprozole (Protonix IV) was approved for short-term treatment of gastroesophageal reflux disease in patients who are unable to take oral medications. The IV dose is the same as oral pantoprozole at 40 mg/d. This approval, however, comes at a time when the use of acid-suppressing therapy and prophylaxis of stress ulcers in the hospital is being scrutinized. A recent meta-analysis looked at the use of IV ranitidine and oral sulcrafate in this role. Ranitidine was no better than placebo in preventing ulcers or GI complications, and when compared to sulcrafate, ranitidine was associated with a higher rate of nosocomial pneumonia (BMJ. 2000;321:1103). The results of this article and others are forcing intensivists to re-evaluate recommendations on the prevention of stress ulcers.

Alternative Medicine

As alternative therapies are objectively evaluated, some are shown to be effective, such as glucosamine (Lancet. 2001;251:251-256), and some are shown to be ineffectual. A recent study from Vanderbilt suggests that St. John’s wort may fall in the latter category. Two hundred patients with major depression were randomized to 8 weeks of St. John’s wort or placebo. The active drug was started at 900 mg/d and increased to 1200 mg/d if there was inadequate response. Depression scores improved slightly in both groups, but there was no significant difference between the two. The active drug group did report more headaches. Shelton and colleagues conclude that there is no evidence that St. John’s wort is effective in treating major depression (JAMA. 2001;285:1978-1986).

More Statin Developments

Statins protect against heart attacks, protect against stroke, and help prevent type 2 diabetes, but do they really reverse osteoporosis? Maybe not according to British researchers who looked at the records of nearly 82,000 patients who suffered fractures, and compared them to the records of 82,000 matched controls. The adjusted odds ratio for fracture among statin users was 1.01 compared to controls. Neither long-term use nor higher doses of statins made a difference (JAMA. 2001;285:1850-1855). These data contradict the results of previous studies that suggested that the drugs may build bone density (JAMA. 2000;283:3205-3216, Lancet. 2000;355:2185-2188).

There may be a new role for statins in the setting of acute coronary syndromes such as unstable angina or acute myocardial infarction. Two recent studies show that statins, when used before or at the time of hospital discharge, reduce subsequent events. One study pooled data from the GUSTO IIb and PURSUIT trials comparing more than 3600 patients with coronary events who were discharged on a statin with more than 17,000 patients who were not discharged on one of the lipid lowering drugs. Both 1-month and 6-month mortality were cut in half in the statin group (Lancet. 2001;357:1063-1068). Atorvastatin (Lipitor) was used in a second study of more than 3000 patients with unstable angina or non-Q-wave MI. The patients, who had an average LDL cholesterol of 124 mg/dL, were randomized to atorvastatin 80 mg/d or placebo. The duration of the study was short, only 16 weeks, but during that time, end points of MI, recurrent angina, cardiac arrest, or death were less common in the treatment group (absolute reduction 14.8% treatment vs placebo, relative reduction of 17.4%). The main benefit was reduction of recurrent symptomatic ischemia requiring rehospitalization. Although the benefit was modest, there seemed to be no risk and few adverse effects from the medication (JAMA. 2001;285:1711-1718).

Alosetron Could Make Limited Return

Glaxo is working with the FDA to allow limited use of alosetron (Lotronex), its drug for women with irritable bowel syndrome. The drug was pulled from the market less than 6 months ago because of cases of ischemic colitis and several deaths associated with the use of the drug. Some of the pressure to reintroduce the drug is coming from patient groups who benefited from the drug. Public Citizen, a consumer advocacy group, is urging the FDA to uphold the ban on alosetron citing evidence that there may have been even more adverse effects than initially reported.

MMR Vaccine and Autism

There is no link between the measles, mumps, rubella (MMR) vaccine and autism according to the findings of a committee commissioned by the Institute of Health. The report, released in April, reviewed all available data and even commissioned its own epidemiologic study. The 15-member expert panel was composed of epidemiologists, pediatricians, biostatisticians, and public health experts picked, in part, because of their lack of ties to the vaccine industry. The concern in this country was heightened in 1998 by a report in Lancet suggesting that the vaccine may be associated with autism-like symptoms. But the current panel exonerates the vaccine, saying it is as "safe as a vaccine can get."