Biogen Idec released the primary efficacy analysis and safety data from its Phase 3 pivotal clinical trial, ADVANCE. Results support Peginterferon beta-1a as a potential treatment dosed every two weeks or every four weeks for relapsing-remitting multiple sclerosis ( RRMS ).
Peginterferon beta-1a is a new molecular entity in which Interferon beta-1a is pegylated to extend its half-life and prolong its exposure in the body, enabling study of a less frequent dosing schedule.

The two-year ADVANCE clinical trial is a global, multi-center, randomized, double-blind, parallel-group, placebo-controlled study designed to evaluate the efficacy and safety of Peginterferon beta-1a in 1,516 randomized patients with relapsing-remitting multiple sclerosis.

The study investigates two dose regimens of Peginterferon beta-1a, 125 mcg administered subcutaneously every two weeks or every four weeks compared to placebo. The analysis for all primary and secondary efficacy endpoints occurs at one year. After the first year, patients on placebo are re-randomized to one of the Peginterferon beta-1a arms for the duration of the second year of the study.

The primary endpoint of ADVANCE, annualized relapse rate ( ARR ) at one year, was met for both the two-week and four-week dose regimens. Results showed that Peginterferon beta-1a also met the secondary endpoints of risk of 12-week confirmed disability progression, proportion of patients who relapsed and magnetic resonance imaging ( MRI ) assessments for both dose regimens.
Adverse events, serious adverse events and discontinuations due to adverse events were similar across both dose groups. Overall with both dose regimens studied, the risk-benefit profile of Peginterferon beta-1a appears to be favorable.

The ADVANCE study included more than 1,500 patients with relapsing-remitting multiple sclerosis and was designed to evaluate the efficacy, safety and tolerability of Peginterferon beta-1a compared to placebo at one year. Results showed that when administered via subcutaneous injection, Peginterferon beta-1a 125 mcg demonstrated a significant reduction in ARR at one year. Compared to placebo, ARR reduction with two-week dosing was 35.6 percent ( p less than 0.001 ) and with four-week dosing was 27.5 percent ( p less than 0.02 ).

Results showed that Peginterferon beta-1a also met all secondary endpoints compared to placebo for both dose regimens.

Peginterferon beta-1a reduced the risk of 12-week confirmed disability progression as measured by the Expanded Disability Status Scale ( EDSS ) by 38% in both dosing arms ( p less than 0.04 ).
Peginterferon beta-1a reduced the proportion of patients who relapsed by 39% in the once every two-week dosing arm ( p less than 0.001 ) and by 26% in the once every four-week dosing arm ( p less than 0.03 ).
Peginterferon beta-1a reduced the number of new or newly enlarging T2-hyperintense lesions on brain MRI scans by 67% in the once every two-week dosing arm ( p less than 0.001 ) and by 28% in the once every four-week dosing arm ( p less than 0.001 ).
In ADVANCE, both dosing regimens showed favorable safety and tolerability profiles. The overall incidence of severe adverse events and adverse events was similar among the Peginterferon beta-1a and placebo groups. The most common severe adverse events was infections, which was balanced across all treatment groups ( less than or equal to 1% per group ).

The most commonly reported adverse events with Peginterferon beta-1a treatment were redness at the injection site and influenza-like illness.

Source: Biogen Idec, 2013

XagenaMedicine2013