Of the 6 adverseevents in which the incidence was 15% or greater,4 (flu syndrome: 132 patients [86%]; headache:64 [42%]; myalgia 29 [ 19%3;and asthenia32 [21%]) are attributable to the flu-like syndrome associatedwith interferon therapy, asalready identified and described in the current label. Paresthesiaoccurred in 31(20%) patients and is also described in the current version of the label. “MS exacerbation” was seenin 41 (27%) patients. Exacerbations are inherent to relapsing MS, though they are not described asadversereactions in the current package insert.
Depression, which is known to be associatedwith MS and potentially with interferon therapy (Vial 1994) was observed in 19patients (12%). There were no reported suicides, suicide attempts, or suicidal tendency in this study. The incidence of depression in this study is similar to that observed in the lyophilized Avonex@-treated group in the pivotal Phase3 (NS 26321) study (15%) but lower than that seenin the clinically isolated symptom (C95-812) study (20%). This may be due to the shorter duration of treatment in the C98-844 study (up to 2 years) compared to the C95-812 study (up to 3 years).
There were no unexpected laboratory abnormalities in this trial. Mild shifts outside of the normal range occurred with an incidence similar to that seenin previous clinical trials with lyophilized AvonexQ.
The overall safety profile observed in C98-844 studying administration of liquid HAS- free Avonex@ administered via pre-filled syringes is similar to that observed with the use of the commercially available lyophilized Avonex@ used in previous clinical studies and marketed in the U.S. since 1996.
Assessment and Conclusions,: The overall safety profile for the liquid HSA-free Avonex@ formulation administered in Biogen Study C94-844 is not substantially or meaningfully different from that reported with the use of the commercially available lyophilized Avonex@ used in previous clinical studies and in clinical practice. This conclusion is basedon the current package insert for Avonex@ along with pre- and post-marketing safety reports, taking into account the different patient populations in which the two formulations havebeen used,the varying durations of exposure to the drug, andthe frequency of ascertainment of adverse reactions and serum neutralizing antibodies.