The announcement, amid a third-quarter report, indicated that the study failed to meet both its main and secondary goals, without further details. The trial, launched in 2017, was expected to be completed in 2022. Whether participants will continue treatment or not is unclear at this point.
Opicinumab (also known as anti-LINGO-1 and BIIB033) is an antibody that works by binding to and blocking the activity of LINGO-1, a protein that suppresses the maturation of myelin-producing cells called oligodendrocytes. Of note, myelin is the protective sheath around nerve fibers that helps to speed transmission of signals between nerve cells, and is damaged and lost in MS.
By blocking LINGO-1, opicinumab was thought to promote myelin repair, an effect that was confirmed in animal models of MS.
This led to the launch of the multi-center Phase 2 SYNERGY study (NCT01864148), which evaluated the safety, tolerability, pharmacokinetics (the therapy’s movement into, through, and out of the body), and effectiveness of opicinumab, in combination with Biogen’s Avonex (interferon beta-1a), in 419 adults with relapsing-remitting MS and secondary progressive MS.
Participants were randomly assigned to receive either one of four doses of opicinumab or a placebo, once every four weeks for 72 weeks (nearly one and a half years), in addition to weekly Avonex injections.
SYNERGY’s main goal was to assess the percentage of patients achieving confirmed functional improvement using a multicomponent measure of disability, physical function, and cognitive function.
The measure consisted of the Expanded Disability Status Scale (EDSS), in which higher scores indicate greater functional impairment; the Timed 25-Foot Walk (T25FW) which measures the time a person takes to walk 25 feet as quickly and safely as possible; and the Nine-Hole Peg Test (9HPT) which assesses finger and hand skills. It also included the three-second Paced Auditory Serial Addition Test (PASAT-3), a measure of cognitive function.
Confirmed benefit was defined as at least a one-point decrease in EDSS scores, or a 15% or greater improvement in any of the other tests for at least three months. Secondary goals included changes in disease progression using the same measures, as well as opicinumab’s safety and pharmacokinetics.
In June 2016, Biogen announced that opicinumab was not superior to placebo at improving patients’ functional capacity and/or at slowing disease progression, meaning SYNERGY had failed both its main and secondary efficacy goals.
However, detailed trial data, announced in 2017 and published in 2019, indicated that a greater proportion of patients given the intermediate doses of opicinumab (10 and 30 mg/kg) showed confirmed functional improvements than those given a placebo (63%–65% vs. 49% in the placebo group).
A more in-depth analysis showed better treatment responses in patients with a disease duration of up to 20 years, and with brain imaging features suggestive of less damage in nerve fibers.
Opicinumab was generally well-tolerated and the safety profile was consistent with that reported in previous studies.
Based on the identification of a patient population potentially more responsive to opicinumab, Biogen launched the international Phase 2b AFFINITY trial (NCT03222973), which evaluated the safety and effectiveness of opicinumab as an add-on to disease-modifying therapies (DMTs) in 263 people with relapsing forms of MS.
Eligible participants had to be on a stable dose of DMT for at least six months prior to enrollment and to meet the brain imaging characteristics suggestive of potentially better response.
Participants were randomly assigned to receive either opicinumab (750 mg) or a placebo once every four weeks for 72 weeks, in addition to their stable DMT.
The trial’s main goal was to assess changes in disability, using the overall response score — a multicomponent measure that included the EDSS score, T25FW test, and 9HPT. Confirmed improvement thresholds were similar to the ones used in SYNERGY. Secondary goals included additional measures of functional improvement.
According to Biogen’s recent announcement, opicinumab did not promote significant functional improvements or halted disability progression, when compared with a placebo, failing to meet both primary and secondary goals of the study.
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