Merck will follow the Zocor model in launching Zetia (ezetimibe) into the cholesterol-lowering class by relying on separate sales forces and a co-promotion partner to establish the new product.

Zetia will be supported by three distinct sales forces when it is launched: one contributed by Merck, one from Zetia-innovator Schering-Plough, and a third sales force under a Merck/Schering joint venture. The Merck sales force devoted to Zetia will be "separate and distinct from Zocor," Merck President-U.S. Human Health & the Americas David Anstice told a Dec. 11 analysts meeting in Whitehouse Station, N.J.

When Merck launched Zocor (simvastatin) in 1992, the company signed up SmithKline Beecham as a co-promotion partner and also assigned the product to a separate sales force from the one detailing Mevacor (lovastatin).

With Zetia, the task of differentiating the product will be simpler than it was with Zocor: ezetimibe is a new mechanism of action agent that will be indicated for use as add-on therapy to statins.

The NDA submission for ezetimibe has already happened or is imminent: Merck says it expects the application to be formally accepted by FDA during the first quarter of 2002.

Merck and Schering-Plough created a joint venture for ezetimibe in May 2000. The companies will also collaborate on development of a fixed combination of Zocor and Zetia (¹ Also see "Merck/Schering Ezetimibe Deal Is Part Of Growing Ties Between Firms" - Pink Sheet, 29 May, 2000., p. 22).

Zetia is the highest profile R&D project at Merck, and the announcement of the brandname, proposed filing schedule and early marketing plans was the first agenda item at the company's annual analysts conference. However, the news was upstaged by Merck's later disclosure that it does not expect earnings in 2002 to grow from the 2001 level (see ² Also see "Merck Re-Sets Expectations For 2002: Zocor, Prilosec Are Possible Upsides" - Pink Sheet, 17 December, 2001. ).

The earnings shortfall is tied to the expected launch of generic versions of Prilosec (omeprazole) in 2002 coupled with lower-than-forecasted Vioxx (rofecoxib) sales.

Once Merck is through the current period of patent expiration, the company will have to reassure investors that it can weather the loss of patent protection for the $7 bil. Zocor franchise, which comes in 2006.

Merck CEO Raymond Gilmartin cautioned analysts against thinking of either Zetia or the Zetia/Zocor combination as a "replacement for Zocor."

Instead, he urged analysts to look at the total package of "eight new breakthrough drugs" that will be coming to market or filed ahead of 2006. "So we enter the 2006 period with a lot of momentum," Gilmartin declared.

One potential complication in the review of Zetia is Schering-Plough's ongoing good manufacturing practices compliance difficulties.

However, Merck maintained that it does not see any delays due to manufacturing issues. "We're confident we'll be able to bring the product to market consistent with timelines approved by the regulatory agency," Anstice said.

The Zocor/Zetia combination is on a slower track than single-agent Zetia; Merck projected a filing in late 2003.

Merck Research Labs President Edward Scolnick, MD, explained that the formulation work for the combination took longer than expected.

The companies are "developing several different tablets," Scolnick noted. Because Zocor was "susceptible to oxidation when we developed it, we had to develop the combination so that none of the various fixed tablets were susceptible to oxidation - which the new formulations now are not."

Scolnick added that "all statins have complex metabolism." Because statins act in the liver, "measuring the blood levels of statin as a surrogate for efficacy is just not a way to go," he said. As a result, Merck needs "to get biochemical efficacy data with all the fixed combinations."

Finally, Scolnick observed, "there are always some inefficiencies in a joint venture."

The availability of Zetia will allow physicians to cut the dose of statins without sacrificing efficacy, Merck said. The combination of Zocor 10 mg and Zetia 10 mg is equivalent to Zocor 80 mg, Scolnick said.

The potential to achieve high-dose statin efficacy levels with lower statin doses may be attractive to prescribers in the wake of the withdrawal of Bayer's Baycol . The drug was associated with fatal cases of rhabdomyolysis at the higher doses. Although Baycol appeared to have a higher rate of cases, the side effect appears to be class related.

"In the entire ezetimibe program, Phase III, there have been no cases of rhabdomyolysis," Scolnick said. The product will allow prescribers to stay within "the safe range for statins," he suggested.

Merck and Schering have a separate joint venture to develop a fixed combination of Merck's asthma agent Singulair and Schering's antihistamine Claritin . During the Dec. 11 meeting, Merck did not highlight that aspect of the joint venture.

The Singulair/Claritin project was not formally discussed, and when asked to provide an update, Scolnick refused to comment beyond saying that clinical research is ongoing.

Schering's manufacturing difficulties may have more of an impact on that aspect of its agreements with Merck. Schering's top priority is gaining approval of the Claritin successor agent Clarinex (desloratadine).

Merck did present data on Singulair for allergic rhinitis, which the company is developing apart from the joint venture. Merck counts the line extension as one of its "breakthrough" projects in development.

Data presented by Merck during the meeting suggest that Singulair is as effective as Claritin in controlling nighttime symptoms of seasonal allergic rhinitis, but not as effective in daytime symptoms.

The company said it intends to file for the new indication in early 2002.

Merck does not expect that an OTC switch for Claritin or the other prescription antihistamines would affect Singulair. "Patients that suffer from allergic Rhinitis are dissatisfied patients," Merck President-Human Health Europe, Africa and the Middle East Per Wold-Olsen said.

"They seek new treatment opportunities. Even if some of the antihistamines would go OTC, they don't do the job, you go to see your doctor and seek better and alternative options. And we fundamentally believe that Singulair would have a lot to offer. Whether antihistamines go OTC or not shouldn't influence our ability to commercialize Singulair in allergic rhinitis."

Merck/Schering Zetia (Ezetimibe) Will Be Supported By Three Sales Forces

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