Novartis Lescol May Be OTC Switch Candidate, Karabelas Says

The safety profile of Novartis' HMG-CoA reductase inhibitor Lescol would support an OTC switch, Novartis Pharmaceuticals CEO Jerry Karabelas suggested at a review of the company's 1997 financial results held March 17 in London.

"Eventually, it is possible that the HMG-CoAs would convert over to OTC status," Karabelas stated. "Lescol has...an ideal profile from a safety point of view," he maintained.

Lescol (fluvastatin) sales advanced 35% to $418 mil. in 1997. Labeling states that "adverse reactions have usually been mild and similar to placebo," based on a database of 2,200 users. Lescol carries a class pregnancy contraindication as well as class warnings about liver and skeletal muscle toxicity.

At launch, Novartis predecessor Sandoz emphasized Lescol's safety status. The firm noted that fluvastatin was the first entirely synthetic HMG-CoA reductase inhibitor and suggested it as a new treatment option for patients who experience problems with other drugs in the class ("The Pink Sheet" March 28, 1994, T&G-7).

No Rx cholesterol-lowering agents have been switched to date, despite two advisory committee reviews of Bristol-Myers Squibb's cholestyramine resin Questran.

Pharmacia & Upjohn's Colestid (colestipol) also is understood to be a switch candidate. In 1995, there also was talk of possible switch attempts for Merck's Mevacor (lovastatin) and Bristol's Pravachol (pravastatin).

Sandoz brought Lescol to market in 1994 at a significant price discount to Merck's Mevacor and Zocor (simvastatin) and Pravachol. With the recent additions of Warner-Lambert's Lipitor (atorvastatin) and SmithKline Beecham/Bayer's Baycol (cerivastatin), the HMG-CoA field now has six prescription drug contenders.

In the case that HMG-CoA inhibitors shift to OTC status, Zocor and Pravachol may have a leg up in at least one safety category: liver function testing. Certain liver function testing requirements recently have been eliminated for both drugs.

Class conditions imposed on all statins have required testing before initiation of treatment, at six and 12 weeks after treatment/elevation of dose, and "periodically thereafter (e.g., semiannually)."

Liver function tests for Zocor now are recommended only prior to the initiation of therapy and periodically (e.g., semiannually) during the first year of therapy or until one year after the last elevation of dose.

Pravachol now requires liver function testing prior to and 12 weeks after therapy begins or dose is elevated.

Unlike Zocor and Mevacor, however, Lescol is not contraindicated in patients receiving Roche's calcium channel blocker Posicor (mibefradil). Posicor labeling also will warn against co-administration with Lipitor and Baycol pending further information ("The Pink Sheet" Dec. 22, 1997, p. 6).

Bayer has emphasized the safety profile of Baycol to differentiate it from competing products. After gaining Baycol approval, the firm said its promotion would focus on the drug's potency and "favorable interaction profile" ("The Pink Sheet" June 30, 1997, p. 3).

Baycol has the ability to reach target LDL cholesterol levels with "significantly less" drug substance than other statins, and has a "favorable interaction profile" with "commonly used drugs" such as warfarin, digoxin, cimetidine and antacids, Bayer said.

In moving toward an OTC product, Merck potentially could take advantage of its gel extrusion module formulation for Zocor 80 mg, currently in Phase III.

The GEM formulation is designed to allow higher doses of drug to be delivered to the liver, where cholesterol is metabolized, with lower amounts reaching the general circulation to minimize potential side effects ("The Pink Sheet" May 26, 1997, T&G-7).

Novartis' Karabelas also said that the antifungal Lamisil (terbinafine) "is really an ideal opportunity" for an OTC switch." Other potential OTC-switch candidates include Voltaren Emulgel, the topical version of the NSAID, he added. Emulgel is not marketed in the U.S.

Lamisil maintained its position as Novartis' number three product and continued to be one of the company's fastest growing drugs, with sales jumping 53% to $616 mil. in 1997.