Schering-Plough is seeing most of the early use of Zetia in either high-risk or statin-intolerant patients, Global Pharmaceuticals President Carrie Cox told investors during a quarterly earnings call Oct. 22.

After 10 months on the market, physicians are prescribing Zetia (ezetimibe) "more than half the time" to patients who are either intolerant to statins or cannot take high doses of the cholesterol-lowering drugs.

Consistent with earlier prescription data, Zetia use is roughly split between co-administration with statins and as monotherapy (¹ Also see "Merck/Schering Zetia Has 50% Combo Use; Statin Of Choice Is Lipitor " - Pink Sheet, 3 February, 2003., p. 27). Of the monotherapy scripts, a "significant percentage is in statin-intolerant patients," Cox noted.

"In the other half, which is combination therapy, you see a very good distribution of Zetia in use with other statins that pretty much reflects the market share of the statin marketplace, so you see primarily Zetia in combination with [Pfizer's] Lipitor ," followed by Merck's Zocor and Bristol-Myers Squibb's Pravachol .

New and total Zetia prescription market share at the end of September was 4.9% and 4.3%, respectively, Cox reported. Zetia generated global sales of $137 mil. during the third quarter, with $122 mil. in the U.S. To date, nearly 3.5 mil. U.S. scripts have been written.

While reporting similar numbers, Zetia co-marketer Merck debated whether new Rx share is an appropriate metric for the drug. "Bear in mind that share for Zetia is probably not the best measure, because it's not competing head-to-head for share," Investor Relations Senior Director Mark Stejbach said on an Oct. 22 call.

"In addition, now you have [AstraZeneca's] Crestor in the market, which while [it] does not have a very large share, is also another product in the denominator. So I do it more as looking at the demand by the total prescriptions as being a better measure for success," Stejbach said.

Schering acknowledged a recent slowdown for Zetia. "Although Zetia volume has continued to increase, recent prescription data has begun to show some deceleration in new and total prescription shares," Cox said.

Pfizer makes similar observations as part of the company's third quarter sales and earnings release.

"Regarding Zetia, its market share in the U.S. in recent weeks has remained relatively flat at 4.9%, indicating that it may have gained initial share from statin-intolerant patients (estimated at about 5% of the market) and is being used in limited cases where statin therapy has not been sufficient to get patients to goal," Pfizer's "Q&A" paper says.

Schering continues to expect that growth will come from patients not reaching their cholesterol targets on statins alone.

"There is clearly much more expansion to be gained in the largest group of patients, those currently being treated with statins alone at any dose, where more than 50% of patients are still not achieving their desired LDL goal," Cox said.

The stakes are high: Schering is heralding Zetia as one of its future growth drivers in the absence of prescription Claritin . Johnson & Johnson's TNF inhibitor Remicade , for which Schering owns European marketing rights, is another "growth driver."

Schering CEO Fred Hassan used the Zetia partnership with Merck as an indication of how the company is operating under new management.

"I can tell you one thing," Hassan told analysts, "Carrie is now more engaged...on Zetia than anyone else before her. It reflects the impact on what we refer to as new thinking and new urgency in our product work."

"We're also seeing new thinking and new urgency bearing fruit in other areas," Hassan continued, citing hepatitis C as one example. "Schering-Plough was the leader in this area, it's a pity that Roche was allowed to gain the advantage. But now we're acting decisively to contain the market share advantages, and eventually to start to push them back."

Schering, once the interferon market leader with Intron A and PEG-Intron (peginterferon alfa-2b), has seen its market share evaporate since the launch of Roche's Pegasys (peginterferon alfa-2a) (² Also see "Pegasys Catching Up To PEG-Intron; Schering Admits “Complacency”" - Pink Sheet, 4 August, 2003., p. 22).

Cox, who has been outspoken about the way in which Schering's former management team handled PEG-Intron in the months following the Pegasys launch, was perhaps even more critical on the third quarter call.

"Schering-Plough has been a weak player, presenting an easy target for the competition," she declared. "The combination of historically poor sales and marketing execution, coupled with poor resource allocation, have put tremendous pressure on many of our product franchises, particularly allergy and hepatitis."

"It took two or three years for Roche to build a presence in this marketplace, and unfortunately it is my opinion that Schering-Plough was not paying adequate attention during that time," Cox said.

"This was a long-term build, and unfortunately, given the length of therapy for each patient and the relatively few number of new patients, it takes time. Once that market share incursion has been made by a competitor, it will take time for us to be able to regain the leadership position, which formerly was ours."

The Pegasys launch has put pressure on PEG-Intron sales. Worldwide sales for Schering's Intron franchise slid 43% to $398 mil. and fell 60% to $171 mil. in the U.S. Fourth quarter comparisons will be even tougher, Cox noted; a "bolus" of wait-listed patients came onto therapy at the end of 2002 as supply became available.

Hassan attributed the sales decline to a number of factors, the biggest of which is the aftermath of the surge in PEG-Intron use in 2002. "This is not a chronic therapy, so some of that patient flow fell off this year."

"On top of that, we've got a very determined competitor that has to some extent succeeded in getting the message across that they are lower in cost because they have had some discounts. They have managed to get the message across that they may have fewer side effects because of the longer half-life, and they seem to have also gotten the message across that they may be the same efficacy as PEG-Intron, even though there is no weight-based dosing."

Hassan also pointed to an inventory scale-down for Rebetol ahead of expected generic competition this year. In addition, "we've had a similar pattern of issues with pent-up demand and then the aftermath in many countries such as Japan. So we're seeing a cumulative effect this year of all of this happening."

The exec acknowledged that the PEG-Intron competitive landscape was not immediately apparent to him when he took office. "When I joined the company, I thought we had big delta this year on the Claritin Rx in the U.S. What I did not recognize was the big delta also on the hep C" franchise.

To regain share, Schering is relying heavily on a head-to-head comparison trial versus Pegasys. The 2,880-patient IDEAL trial will help "clear up misconceptions in the marketplace about these two treatments," the company said.

The IDEAL trial will compare the efficacy and safety of individualized weight-based dosing with PEG-Intron and Rebetol (ribavirin) versus a "flat dose" of Pegasys and Copegus (ribavirin) either at 1,000 mg or 1,200 mg. Schering says the two treatment regimens have never before been compared.

"The major focus with the IDEAL trial is to clarify in the minds of physicians that we believe PEG-Intron is the superior product. A lot of this is based on the fact that individualized weight-based dosing just makes more sense in this marketplace," Cox said.

"With PEG-Intron, we have put our money where our mouth is," she declared. "To do a head-to-head trial between these two products clearly indicates our belief in the superiority of PEG-Intron."

"The real answer comes down to which product is going to perform better in terms of creating more positive patient outcomes," she said. "Customers are quite pleased to see that, because they understand...that if we believe so strongly that PEG-Intron is superior, that's having an impact on their perception."

"At this point, we are not aware that physicians really see any differences between the products, in fact, and if anything...there is a potential advantage with PEG-Intron because of weight-based dosing."

PEG-Intron's efficacy may also be easily predicted. In a recently published study in Hepatology, 74% of PEG-Intron patients demonstrated an early virologic response following 12 weeks of therapy, and of those, 72% achieved a sustained response after 48 weeks.

"This is a major advantage for patients who can undergo three months of therapy and then...have the ability to predict a longer-term response, rather than having to continue a difficult therapy without the assurance of an expected outcome," Cox said.

Schering pointed to its single-use, self-injectable pen Redipen as another differentiating feature for PEG-Intron. Redipen, which was recently cleared by FDA, "will be a unique advantage for some period of time, only available with PEG-Intron," Cox said. Schering will launch Redipen in early 2004.

Merck/Schering Zetia Early Use Is In High-Risk Patients; New Rx Share At 5%

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