Janssen's discontinuation of Hismanal prior to the introduction of Sepracor's norastemizole will allow for greater differentiation of the metabolite as a separate product from the parent compound instead of as a follow-on.

Janssen announced June 21 that it is withdrawing the nonsedating antihistamine Hismanal (astemizole) from the market. Sepracor is not planning an NDA filing for norastemizole, the active metabolite of astemizole, before the end of 2000.

The introduction of Hoechst Marion Roussel's Allegra (fexofenadine), also developed by Sepracor, before the removal of its topselling drug Seldane (terfenadine) from the market was a boon for Allegra, because Seldane patients could be switched to the newer therapy. Seldane had similar cardiovascular risks as Hismanal. However, Hismanal's market share would not provide a similar benefit for norastemizole.

Janssen indicated that the decision to voluntarily discontinue manufacturing Hismanal is attributable to the product's relatively weak performance in the crowded antihistamine market. Janssen noted that "the company is taking this action after careful consideration of the antihistamine class, which includes multiple alternative medications."

IMS Health reported Hismanal sales from May 1998 through April 1999 were $24.6 mil., a 43% decrease from the same period during the previous year.

After several labeling revisions for serious cardiac side effects, Hismanal's U.S. sales had dwindled to $6.56 mil. from January to April 1999. By comparison, Schering-Plough's market leader Claritin (loratadine) had U.S. sales of $410 mil. from January to April; Hoechst posted sales of $128.3 mil. for Allegra; and Pfizer's Zyrtec (cetirizine) sales were $149 mil. for the period.

The decision by Janssen parent Johnson & Johnson to neither co-promote nor co-develop norastemizole with Sepracor may have foreshadowed Janssen's voluntary discontinuation of Hismanal. J&J opted instead to receive royalties on norastemizole sales at a rate of approximately 5% ("The Pink Sheet" May 24, p. 20).

The Hismanal NDA will remain at FDA. As part of the norastemizole deal with J&J, Sepracor acquired rights to reference the Hismanal NDA, which the company said it still plans to do.

Hoechst opposed FDA's withdrawal of its Seldane NDA even after the company had withdrawn the product from the market in February 1998 because of cardiac adverse event reports. FDA finally withdrew the NDA in October of that year.

Hismanal labeling has undergone two revisions, once in 1992 and then again in 1998. The labeling changes were made in order to address the postmarketing cardiovascular risks.

Labeling revisions have included a black box warning regarding risk of QT prolongation, as well as a list of drug products for which labeling advises against co-administration. Included on that list are certain antibiotics, antifungals, selective serotonin reuptake inhibitors and grapefruit juice ("The Pink Sheet" Feb. 9, 1998, T&G-1).

While there does not appear to be an increase in adverse event reports related to Hismanal therapy, FDA noted that the significant decrease in use could be masking continued or elevated risk.

FDA has endorsed Janssen's action, stating that, "in light of the choices of other prescription antihistamines now available, and the overall risk/benefit profile of this drug, FDA supports the decision of the company to withdraw the product."

Janssen issued a letter to health care professionals June 18 alerting them of the Hismanal discontinuation. The company advised physicians and pharmacists to consider alternative therapies to Hismanal.

The company will field calls from patients and medical professionals requiring additional information about the company's action through its "One to One Customer Action Center."

Hismanal manufacturing will be discontinued on an international basis. In June 1998, availability of the product in the U.K was limited to prescription use only in the wake of cardiovascular adverse event risks. It was previously available over the counter ("The Pink Sheet" June 29, 1998, p. 15).

Hismanal Withdrawal Will Allow Sepracor To Define Metabolite As New Drug

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