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of Antigenicity


In C98-844, the incidence of binding (vs. neutralizing,


are shown above)

antibodies to liquid


Avonex@ was 13.6% at Month

12 and23.1% at Month


In study C94-801, in which patients received lyophilized AvonexGB,the incidence of binding antibodies in patients with no prior exposure to interferon beta was 17% at Month 12 and28% at Month 21 All theseresults arenot substantially different, despite the fact that they were studied in different groups of patients.

Similarly, in C98-844, the incidence of neutralizing antibodies measured in patients treated with liquid HSA-free Avonex@ administered with pm-filled syringes is not substantially different from the incidences reported following treatment with lyophilized Avonex@ in clinical studies. At the time of this interim study report for C98-844,3.3% of subjects hadneutralizing antibody titers ~20 at sometime during the course of the study

using liquid HAS-free Avonex@ pre-filled syringes.


’R L

Study C95-812 was a double-blind, randomized

study to determine if the currently approved lyophilized Avonex@ was beneficial in delaying the diagnosis of clinically definite MS in subjects who experienced a first and recent onset of a demyelinating and who were at high risk of developing MS based on the presenceof multiple brain MRI abnormalities (Jacobs 2000). Subjects received 30 mcg of

AVONEXe IM once weekly for up to 36 months. No subjectswere reported to test . positive for neutralizing antibodies at baseline. In this study, the incidence of subjects

developing NAB titers 25 was reportedto be 3.4%; with titers >20 the incidence was reported to be 1.7%. Again, one can conclude from these reports that the incidence of the occurrence of neutralizing antibodies after receiving liquid HSA-flee Avonex@ and the

commercially available lyophilized product arenot substantially different, taking into account the differences in the patient populations studied, the numbers of patients tested in each study, the varying durations of exposure, andthe numbers of samples analyzed.

A theoretical concern with neutralizing antibody formation is allergic reactions and injection site reactions. The incidence of adverseevents in relationship to antibody status is presentedin Table 2. Overall, the incidence of adverseevents in neutralizing antibody- positive subjects is not different comparedto neutralizing antibody-negative subjects.

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