FDA Approves SINGULAIR For Seasonal Allergic Rhinitis; A New Class of Therapy for the Treatment of Seasonal Allergic Rhinitis -Also Known as Hay Fever-

Business Wire, Jan 2, 2003

Clinical Studies - Asthma and Seasonal Allergic Rhinitis

GENERAL

There have been no clinical trials in asthmatics to evaluate the relative efficacy of morning versus evening dosing. The pharmacokinetics of montelukast are similar whether dosed in the morning or evening. Efficacy has been demonstrated for asthma when montelukast was administered in the evening without regard to time of food ingestion. Efficacy was demonstrated for seasonal allergic rhinitis when montelukast was administered in the morning or the evening without regard to time of food ingestion.

Clinical Studies - Asthma

ADULTS AND ADOLESCENTS 15 YEARS OF AGE AND OLDER

Clinical trials in adults and adolescents 15 years of age and older demonstrated there is no additional clinical benefit to montelukast doses above 10 mg once daily. This was shown in two chronic asthma trials using doses up to 200 mg once daily and in one exercise challenge study using doses up to 50 mg, evaluated at the end of the once-daily dosing interval.

The efficacy of SINGULAIR for the chronic treatment of asthma in adults and adolescents 15 years of age and older was demonstrated in two (U.S. and Multinational) similarly designed, randomized, 12-week, double-blind, placebo-controlled trials in 1576 patients (795 treated with SINGULAIR, 530 treated with placebo, and 251 treated with active control). The patients studied were mild and moderate, non-smoking asthmatics who required approximately 5 puffs of inhaled (beta)-agonist per day on an "as-needed" basis. The patients had a mean baseline percent of predicted forced expiratory volume in 1 second (FEV1) of 66% (approximate range, 40 to 90%). The co-primary endpoints in these trials were FEV(1) and daytime asthma symptoms. Secondary endpoints included morning and evening peak expiratory flow rates (AM PEFR, PM PEFR), rescue (beta)-agonist requirements, nocturnal awakening due to asthma, and other asthma-related outcomes. In both studies after 12 weeks, a random subset of patients receiving SINGULAIR was switched to placebo for an additional 3 weeks of double-blind treatment to evaluate for possible rebound effects. The results of the U.S. trial on the primary endpoint, FEV(1), expressed as mean percent change from baseline, are shown in FIGURE 1.

                               FIGURE 1
                FEV1 Mean Percent Change from Baseline
                             (U.S. Trial)

                           (GRAPHIC OMITTED)

    The effect of SINGULAIR on other primary and secondary endpoints
is shown in TABLE 1 as combined analyses of the U.S. and Multinational
trials.

                              TABLE 1
           Effect of SINGULAIR on Primary and Secondary Endpoints
                     in Placebo-controlled Trials
           (Combined Analyses - U.S. and Multinational Trials)

------------------------- ---------------------- ---------------------
                          ---------------------         Placebo
                                 SINGULAIR
------------------------- ---------------------- ---------------------
------------------------- ---------- ----------- ----------- ---------
Endpoint                  Baseline   Mean         Baseline   Mean
                                     Change                  Change
                                     from                    from
                                     Baseline                Baseline
------------------------- ---------- ----------- ----------- ---------
------------------------- ---------- ----------- ----------- ---------
Daytime Asthma Symptoms     2.43       -0.45(b)     2.45       -0.22
(0 to 6 scale)
------------------------- ---------- ----------- ----------- ---------
------------------------- ---------- ----------- ----------- ---------
(beta)-agonist (puffs       5.38       -1.56(b)     5.55       -0.41
per day)
------------------------- ---------- ----------- ----------- ---------
------------------------- ---------- ----------- ----------- ---------
AM PEFR (L/min)             361.3      24.5(b)     364.9        3.3
------------------------- ---------- ----------- ----------- ---------
------------------------- ---------- ----------- ----------- ---------
PM PEFR (L/min)             385.2      17.9(b)     389.3        2.0
------------------------- ---------- ----------- ----------- ---------
------------------------- ---------- ----------- ----------- ---------
Nocturnal Awakenings        5.37       -1.84(b)    5.44       -0.79
(#/week)
------------------------- ---------- ----------- ----------- ---------

(b) p (less than) 0.001, compared with placebo