Norastemizole Sepracor

Sepracor and Janssen are developing the histamine H1 antagonist, norastemizole (an active metabolite of Johnson & Johnson's Hismanal), for the potential, non-sedating treatment of allergy. Sepracor expects to file an NDA with the FDA by the fourth quarter of 2000 [337315,358429]. As of September 1999, Sepracor was conducting two large-scale phase III seasonal allergic rhinitis studies [340260]. Sepracor expects norastemizole to be the most potent non-sedating histamine, with equal or more rapid onset of action than other therapies [229516]. Norastemizole is 13- to 16-fold more potent as an H1 antagonist than astemizole and 20- to 40-fold more potent in inhibiting histamine-induced bronchoconstriction. Following a single dose of norastemizole (25 mg p.o.), there is significant attenuation of histamine-induced wheal and flare responses within 30 min. The drug's major advantage is its lack of cardiotoxicity or interactions with other drugs that increase the risk of developing serious arrhythmias [301469]. In July 2000, Morgan Stanley Dean Witter predicted filing for FDA approval for allergic rhinitis during the first half of 2001, and a partnership announcement around the time of this NDA filing. The analysts also forecast European sales of $8.3 million in 2002, rising to $16.7 m by 2005 [384868].