Executive Summary

ALZA/MERCK ONCE-DAILY DILTIAZEM AND DILTIAZEM/VASOTEC COMBO are being "clinically evaluated" by Merck, Alza said March 8. The drug delivery technology firm Alza and the cardiovascular leader Merck have a licensing agreement covering the calcium channel blocker diltiazem (Marion Merrell Dow's Cardizem) and a diltiazem/enalapril (Merck's ACE inhibitor Vasotec) combo in once-a-day oral dosage forms. The dosage forms employ an osmotic controlled-release technology to which both firms contributed. Alza is not specifying if the technology is based on its proprietary Oros osmotic release system. Neither is Alza disclosing at what stage the products are in the development process. Merck would market both products worldwide under a royalty-bearing agreement with Alza. Importantly for Alza, the agreement would allow the firm to retain some undisclosed U.S. marketing rights. The licensing agreement is several years old but was not previously disclosed by Alza in public presentations. The renewal of joint development efforts by Alza and Merck indicates a rapprochement between the two firms after a fall-out over Merck's 1983 European market withdrawal of the Oros-system indomethacin product Osmocin. Merck withdrew the product and dropped U.S. development efforts after adverse reaction reports in Europe ("The Pink Sheet" Jan. 23, 1984, T&G-4). A sustained-release diltiazem would fill one of the few remaining gaps in Merck's strong cardiovascular armamentarium. The company is lacking an approved calcium channel blocker at the moment; an NDA is pending for Splendil (felodipine, formerly dubbed Plendil) for hypertension. Merck already markets two ACE inhibitors, Vasotec and Prinivil; the beta blocker Blocadren; the anti-arrhythmic Tonocard; the potassium-sparing diuretic Moduretic; and the older antihypertensive Aldomet. Alza/Merck is in a race with a number of competitors for once-daily diltiazem, including Marion Merrell Dow and Rorer, which maintains a joint venture with Bolar for a once-a-day product ("The Pink Sheet" July 24, T&G-6). Exclusivity for immediate release Cardizem expires Nov. 5, 1992, and protection for the twice-daily product, Cardizem SR, runs out in 1993. Also working on once-a-day diltiazem is Elan, which is working with Marion Merrell Dow on Diltelan; Noven is in early development for another transdermal form, and Verex is developing a once-daily form called Verzem.