Schering-Plough's discounted pricing for the antihistamine Clarinex follows the model used by AstraZeneca to launch the anti-ulcer agent Nexium .

Schering is launching desloratadine at a 17.5% discount to Claritin (loratadine). Schering said the net direct price for Clarinex will be $1.83 for a 5 mg once-daily dose versus $2.22 for a 10 mg daily dose of the parent compound.

The pricing strategy parallels the approach used by AstraZeneca for the Prilosec (omeprazole) successor Nexium (esomeprazole). Nexium is priced at a 3.5% discount to the lower dose of Prilosec, and at a 33% discount to the higher dose.

In both cases, the manufacturers are facing tight deadlines to establish the successor ahead of generic competition for the original product. The discounted price provides a clear point of differentiation to help kick start the launch of the newer versions.

Clarinex is still at the high end of prices in the antihistamine category. The list price will be at roughly the same level as Aventis' Allegra (fexofenadine), and above Pfizer's Zyrtec (cetirizine).

Desloratadine was approved by FDA on Dec. 21 (¹ Also see "Schering Clarinex Approval Comes In Time For Big Spring Push" - Pink Sheet, 24 December, 2001., p. 34). The NDA was pending at FDA for more than two years; for the last 11 months approval was contingent on resolution of manufacturing difficulties (see ² Also see "Clarinex Approval Precedes Consent Decree, But Follows Schering GMP Work" - Pink Sheet, 7 January, 2002.).

Clarinex labeling does not provide any clear advantages over Claritin.

Schering, however, sees a potentially longer duration of action for Clarinex that it could emphasize in marketing. The company says clinical research shows that Clarinex has a consistent significant effect at 12 and 24 hours. The research is not included in labeling.

While Claritin is approved for 24-hour dosing, Schering says internal market research has shown that some people do not feel the same symptom relief upon awakening after taking a dose the day before. The company added that it has not done studies to test the consistency of the Claritin effect at 12 and 24 hours.

Schering maintains it will steer clear of comparisons to existing non-sedating antihistamines in its promotions.

In Europe, Schering attempted to craft a faster onset of action claim, based on the 1-2 hour onset cited in the European Public Assessment Report (³ Also see "Schering Desloratadine Onset Of Action Is 1-2 Hours - EU Review Document" - Pink Sheet, 26 March, 2001., p. 13).

FDA-approved labeling does not support the claim, putting the onset of action in the same range as other antihistamines. The U.S. label says that Clarinex reaches peak plasma levels in three hours, while Claritin labeling says maximum concentration is achieved in 1.3 hours. Clarinex' mean elimination half-life is 27 hours, compared to 8.4 hours for Claritin.

The timing of the approval gives Schering an opportunity to build its presence in advance of the spring allergy season. The company will have at least one more allergy season in the fall to establish Clarinex before generic versions of Claritin are available.

Generics companies hope to bring loratadine to market in December 2002, when Schering's first Claritin patent (plus a pediatric exclusivity extension) expires. Schering, however, is defending a second loratadine patent that runs until October 2004.

AstraZeneca launched Nexium in March; the first generic version of Prilosec could enter the market by the second quarter of 2002, depending on the outcome of patent litigation.

Nexium has performed well in its first year on the market, reaching a 15% share of the huge proton pump inhibitor market as of mid-November (⁴ [A#00630500014], p. 20). However, it has a long way to go to replace Prilosec in terms of sales volume: third quarter sales of Nexium in the U.S. were $138 mil., compared to $970 mil. for Prilosec.

The performance of Nexium once generic omeprazole is available could also provide a test of how Clarinex will hold up once generic versions of loratadine are launched.

Managed care companies have not historically been able to shift patients from one drug in a therapeutic category to a cheaper competitor in the same class. However, close molecular similarity between the parent and successor compounds will presumably encourage MCOs to make an aggressive attempt to shift Clarinex and Nexium patients to generic Claritin or Prilosec.

The possibility of an over-the-counter switch for Claritin is another complication for Schering. The Center for Drug Evaluation & Research hoped to reach a decision on Wellpoint's petition requesting a forced switch of Claritin, Allegra and Zyrtec before the end of the year (⁵ 'The Pink Sheet' Nov. 26, 2001, In Brief).

The agency's final decision will require a legal analysis of the issues raised by the petition, and any attempt to force a Claritin switch would presumably face a court challenge from Schering.

Clarinex was approved for nasal and non-nasal symptoms of seasonal allergic rhinitis based on four placebo-controlled pivotal studies in a total of 2,300 patients 12 to 75 years of age. "A total of 1,838 patients received 2.5-20 mg/day of Clarinex in four double-blind, randomized, placebo-controlled clinical trials of 2-4 weeks duration," labeling notes.

The trials relied on a total nasal symptom score as the primary endpoint. Over a two-week clinical trial a statistically significant change from baseline of -4.3 was seen in 171 patients on Clarinex, compared to -2.5 in 173 placebo patients.

No benefit was seen in doses higher than 5 mg, although "an increase in the incidence of somnolence was observed at doses of 10 mg/day and 20 mg/day (5.2% and 7.6% respectively), compared to placebo (2.3%)," labeling states. Patients are advised "not to increase the dose or dosing frequency as studies have not demonstrated increased effectiveness at higher doses, and somnolence may occur."

The most common adverse events reported during Clarinex clinical trials, occurring at similar rates to placebo, include: pharyngitis 5%, dry mouth 4%, somnolence 3% and fatigue 3%.

Labeling also includes spontaneous adverse events from postmarketing experience in Europe: "tachycardia, and rarely hypersensitivity reactions (such as rash, pruritis, urticaria, edema, dyspnea and anaphylaxis), and elevated liver enzymes including bilirubin."

Clarinex labeling refers to a subset of the general population who are slow desloratadine metabolizers. Of 1,087 patients in pharmacokinetic studies "approximately 7% of subjects were slow metabolizers," with a six-fold greater median exposure.

"Subjects who are slow metabolizers of desloratadine cannot be prospectively defined and will be exposed to higher levels of desloratadine following dosing," labeling notes. "Although not seen in these pharmacokinetic studies, patients who are slow metabolizers may be more susceptible to dose-related adverse events."

Schering has one Phase IV commitment for Clarinex; the company is conducting a carcinogenicity study, which it describes as routine. Labeling states that "the carcinogenic potential of desloratadine was assessed using loratadine studies." Loratadine's carcinogenic potential was extensively studied as part of the protracted NDA review for that product.

Schering has received a written request for pediatric studies.

Schering-Plough Clarinex Launch Strategy Follows Nexium Model

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