Promising Antiviral Drug in Phase II Studies

By William T. Elliott, MD, FACP

Two new quinolone antibiotics have been approved by the fda. Bayer’s moxifloxacin (Avelox) was approved for once-daily treatment of respiratory infections. The drug is effective against common respiratory pathogens including pneumococcus, H. influenzae, and Moraxella catarrhalis. Moxifloxacin is given as a 400-mg dose, once a day for 5-10 days, and is approved for the treatment of acute bacterial exacerbations of chronic bronchitis, community acquired pneumonia, and bacterial sinusitis. Bristol-Myers Squibb is also launching gatifloxacin (Tequin) for the treatment of upper and lower respiratory infections, urinary tract infections, and gonorrhea. Gatifloxacin is available in both an oral and intravenous form. Both drugs are only approved for adults age 18 and older.

Real progress has been made on antiviral drugs in the last few years. Late 1999 saw the approval of two anti-influenza drugs. Now, Agouron Pharmaceuticals has announced progress in the development of an anti-rhinovirus medication. Rhinoviruses are the most frequent cause of the common cold. The drug, AG7088, is an inhaled rhinovirus 3C protease inhibitor. The company reports "significant improvement in total cold symptoms" in patients deliberately exposed to rhinovirus. Phase II trials of the drug in naturally acquired colds are in progress.

Antiarrhythmic therapy with drugs, even if it is guided by electrophysiologic studies, has no effect on the risk of sudden death in high risk coronary disease. That is the finding of a study of more than 700 patients published in December 1999 (N Engl J Med 1999;341:1882-1890). This confirms previous studies that empirical therapy in these patients is of no value. A second part of the study evaluated the role of implantable defibrillators in the same role. The survival benefit was significant with these devices, with a reduction in five-year mortality from 37% (no defibrillator) to 9% (implantable defibrillators). All patients in the study had ejection fractions below 40% and asymptomatic, nonsustained ventricular tachycardia.

Protease inhibitors have been associated with lipodystrophy, hypercholesterolemia, insulin resistance, and even premature CAD. Now there is a report that these drugs may also be associated with venous thromboembolism. Researchers from the University of Iowa report 11 episodes of venous thrombosis or pulmonary embolism in seven HIV-infected patients. These patients were otherwise healthy individuals who were receiving protease inhibitors. The drugs used in these patients were ritonavir, nelfinavir, saquiniavir, and indinavir (Am J Med 1999;107:624-626). It is felt that the drugs may interfere with hepatic regulation of clotting proteins resulting in a prothrombotic state.

Niacin may increase homocysteine levels in patients who are being treated for hypercholesterolemia. Fifty-two patients with peripheral arterial disease were randomized to receive 1-3 g of niacin daily, or placebo. At 18 weeks, the 25 patients in the niacin group averaged a 55% increase in homocysteine levels from baseline (Am Heart J 1999;138:1082-1087). The effect may be blunted by a daily dose of folate or vitamin B6. Elevated homocysteine levels have been implicated as a risk factor in the development of atherosclerosis.

Anecdotal reports have suggested that secretin might be effective as a treatment for children with autism. The National Institute of Child Health and Human Development recently tested a single intravenous dose of secretin or placebo in 60 autistic children. The drug showed no efficacy in any of the outcome measures (N Engl J Med 1999;341:1801-1806). This study was disappointing for many parents of autistic children, but despite the findings, the majority of parents of the children in the study were planning on pursuing further secreting treatments.

FDA News:

Allergan has received clearance to market a new eye drop for allergic conjunctivitis. Nedocromil sodium (Alocril) stabilizes mast cells and decreases activation of other allergic mediators. The agency has also approved the first topical treatment for onychomycosis. German manufacturer Aventis will market topical ciclopirox as Penlac Nail Lacquer Topical Solution 8%. Daily application is required for as long as 48 weeks to treat fungal nails.

Pending final FDA approval, SmithKline Beecham will market a new OTC cream for the treatment of oral-facial herpes. Docosanol 10% cream is expected to receive final approval early this year. A trade name has not yet been decided.