Novartis Plans Chronic Constipation Disease Ads Following Zelnorm Approval

Novartis plans to begin a patient-directed disease awareness campaign on chronic constipation in 2005.

FDA cleared Novartis' irritable bowel syndrome agent Zelnorm for the treatment of chronic idiopathic constipation in male and female patients under 65 years of age Aug. 21.

The company said it is still devising its strategy for patient promotions. Initially, Novartis intends to design patient-directed communications to help patients overcome any stigma associated with chronic constipation.

Physician detailing will begin within a month and will have a similar disease awareness focus.

Novartis credited a direct-to-consumer ad campaign for Zelnorm's constipation-predominant irritable bowel syndrome indication with helping the brand "take off" (¹ (Also see "Novartis Sales Growth Strategy Is DTC Ads, “Cleverly Crafted” Phase IVs" - Pink Sheet, 27 Oct, 2003.), p. 33). There are no plans currently to initiate product specific DTC ads for the new indication, the company said.

The non-gender specific chronic constipation indication will give Novartis a larger patient base from which to draw users than it has for IBS, which is approved for use by women only.

In approving the broader chronic constipation indication, FDA bucked the recommendation of a majority of its Gastrointestinal Drugs Advisory Committee. In July, the committee voted 10-3 to recommend approval, but eight of those 10 members said use of tegaserod should be limited to women under age 65 (² (Also see "Zelnorm For Chronic Constipation Should Exclude Males And Seniors – Cmte." - Pink Sheet, 19 Jul, 2004.), p. 7).

In clinical trials, 91% of the patients were female and the efficacy rate in males was lower.

³ Labeling notes that "the effectiveness of Zelnorm in patients 65 years of age or older...has not been established." Zelnorm also is not indicated for use in patients less than 18 years of age.

The FDA ⁴ approval letter states that Novartis will conduct a post-marketing study to "assess/monitor the age distribution of Zelnorm recipients in the U.S."

The program should be "based on U.S. prescription data and would result in data representative of the U.S. population for patients" greater than 65 years of age or less than 16 years of age.

As a second Phase IV commitment, Novartis will assess the distribution of the Zelnorm "Medguide" to patients (see ⁵ (Also see "Novartis To Assess Zelnorm “Medguide” Distribution In Phase IV Study" - Pink Sheet, 30 Aug, 2004.) ).

Several advisory committee members suggested limiting therapy to 12 weeks to reflect the duration of use in clinical trials.

Labeling states: "The efficacy of Zelnorm for the treatment of IBS with constipation or chronic idiopathic constipation has not been studied beyond 12 weeks."

In addition, the dosage section says "physicians and patients should periodically assess the need for continued therapy."

The recommended duration of therapy for the IBS indication is four to six weeks, though an additional four to six weeks may be considered for responders.

For both indications, labeling recommends a dose of 6 mg b.i.d. taken orally before meals.

In two pivotal chronic constipation trials, 40.2% and 43.2% of patients receiving 6 mg b.i.d. tegaserod had an increase of at least one complete spontaneous bowel movement per week during the first four weeks of therapy with at least seven days of active treatment, according to ⁶ Novartis documents prepared for the advisory committee.

A 2 mg b.i.d. dose was also studied; response rates over the two trials were 35.6% and 41.4%, compared to placebo response rates of 26.7% and 25.1%, respectively.

Labeling states that patients taking 2 mg b.i.d. "showed significant changes during the first four weeks," but "no statistically significant changes were observed over 12 weeks in one study."

By comparison, the 6 mg b.i.d. dose results were "statistically significant for [complete spontaneous bowel movement] changes averaged over the first 4 weeks of treatment and the full 12 weeks of treatment."