Contributions
Abstract: EP1619
Type: Poster Sessions
Abstract Category: Therapy - Neuroprotection and Repair
Introduction: Opicinumab is a human monoclonal antibody against LINGO-1, a negative regulator of oligodendrocyte differentiation and axonal regeneration. Data from the phase 2 SYNERGY study identified a dose (10 mg/kg) and a subpopulation (defined by disease duration and baseline MRI characteristics) that were associated with an enhanced treatment response and thus merit further investigation.
Objectives: To present the rationale for and design of the AFFINITY study (NCT03222973) and participant baseline characteristics.
Methods: AFFINITY is a phase 2, 72-week, multicentre, randomised, double-blind, placebo-controlled study to evaluate the efficacy/safety of opicinumab (intravenous 750 mg every 4 weeks) versus placebo as an add-on to disease-modifying therapies (DMTs) in a targeted population with relapsing MS. Inclusion criteria include: age 18-58 years with relapsing-remitting or secondary progressive MS; disease duration ≤20 years; Expanded Disability Status Scale (EDSS) 2.0-6.0; clinical relapse between 24 weeks-24 months or brain MRI evidence of disease activity ≤24 months; stable on interferon beta, dimethyl fumarate, or natalizumab for ≥24 weeks; and characteristics on magnetisation transfer ratio and diffusion tensor imaging-radial diffusivity suggestive of lower myelin content and more preserved tissue integrity in brain T2 lesions. The primary endpoint is the Overall Response Score, an integrated assessment of disability improvement and worsening based on the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT; dominant and non-dominant). Secondary endpoints include the proportion of patients with confirmed improvement in disability measures including EDSS, T25FW, 9HPT, 3-Second Paced Auditory Serial Addition Test, and Symbol Digit Modality Test.
Results: The study was started in September 2017, and enrolment is ongoing. AFFINITY is expected to enrol ~240 participants at ~150 sites in ~25 countries. Baseline demographic, disease and MRI characteristics of enrolled participants will be presented.
Conclusions: AFFINITY will further investigate the efficacy and safety of opicinumab as an add-on therapy to anti-inflammatory DMTs in a subpopulation of patients with MS (disease duration ≤20 years, lower myelin content and more preserved tissue integrity) with potentially enhanced responses to opicinumab.
Disclosure: Supported by: Biogen (Cambridge, MA, USA). Writing and editorial support for the preparation of this abstract was provided by Excel Scientific Solutions (Southport, CT, USA): funding was provided by Biogen.
B. Zhu, P. Wolstencroft, K. Johnson, S. Liu, I. Chang, A. Deykin, and S. Sheikh are employees of and hold stock/stock options in Biogen.
P. A. Calabresi has received consulting fees from Biogen and Disarm Therapeutics; is associate editor of The Journal of Clinical Investigation; and has received research support/grants to his institution from Annexon Biosciences, Biogen, MedImmune, Novartis and Sanofi.
G. Giovannoni is on advisory boards for AbbVie Biotherapeutics Inc., Almirall, Atara Biotherapeutics, Biogen, Merck, Merck Serono, Novartis, Roche, Sanofi-Genzyme and Teva; has received speaker fees from AbbVie Biotherapeutics Inc., Biogen, Genzyme, Merck, Merck Serono, Sanofi-Genzyme and Teva; is co-editor in chief of Multiple Sclerosis and Related Disorders; and has received research support unrelated to study from Biogen, Genzyme and Novartis.
R. Kapoor has received personal fees and/or travel support from Biogen, Genzyme and Roche; and is on clinical trial steering committees for Biogen.
R. Naismith has received consulting/speaker fees from Acorda, Alkermes, Biogen, EMD Serono, Genentech, Genzyme, Novartis and Teva.
H-P. Hartung has received speaker fees/travel expense reimbursement from and is on steering committees/advisory boards for Biogen, Geneuro, Genzyme, Merck, Medimmune, Novartis, Octapharma, Opexa, Receptos, Roche, Sanofi-Aventis and Teva.
D. L. Arnold has received personal fees for consulting from Acorda, Biogen, Hoffman La Roche, MedImmune, Mitsubishi, Novartis, Receptos, and Sanofi-Aventis; equity interest in NeuroRx Research; and grants from Biogen and Novartis.
Abstract: EP1619
Type: Poster Sessions
Abstract Category: Therapy - Neuroprotection and Repair
Introduction: Opicinumab is a human monoclonal antibody against LINGO-1, a negative regulator of oligodendrocyte differentiation and axonal regeneration. Data from the phase 2 SYNERGY study identified a dose (10 mg/kg) and a subpopulation (defined by disease duration and baseline MRI characteristics) that were associated with an enhanced treatment response and thus merit further investigation.
Objectives: To present the rationale for and design of the AFFINITY study (NCT03222973) and participant baseline characteristics.
Methods: AFFINITY is a phase 2, 72-week, multicentre, randomised, double-blind, placebo-controlled study to evaluate the efficacy/safety of opicinumab (intravenous 750 mg every 4 weeks) versus placebo as an add-on to disease-modifying therapies (DMTs) in a targeted population with relapsing MS. Inclusion criteria include: age 18-58 years with relapsing-remitting or secondary progressive MS; disease duration ≤20 years; Expanded Disability Status Scale (EDSS) 2.0-6.0; clinical relapse between 24 weeks-24 months or brain MRI evidence of disease activity ≤24 months; stable on interferon beta, dimethyl fumarate, or natalizumab for ≥24 weeks; and characteristics on magnetisation transfer ratio and diffusion tensor imaging-radial diffusivity suggestive of lower myelin content and more preserved tissue integrity in brain T2 lesions. The primary endpoint is the Overall Response Score, an integrated assessment of disability improvement and worsening based on the EDSS, Timed 25-Foot Walk (T25FW), and 9-Hole Peg Test (9HPT; dominant and non-dominant). Secondary endpoints include the proportion of patients with confirmed improvement in disability measures including EDSS, T25FW, 9HPT, 3-Second Paced Auditory Serial Addition Test, and Symbol Digit Modality Test.
Results: The study was started in September 2017, and enrolment is ongoing. AFFINITY is expected to enrol ~240 participants at ~150 sites in ~25 countries. Baseline demographic, disease and MRI characteristics of enrolled participants will be presented.
Conclusions: AFFINITY will further investigate the efficacy and safety of opicinumab as an add-on therapy to anti-inflammatory DMTs in a subpopulation of patients with MS (disease duration ≤20 years, lower myelin content and more preserved tissue integrity) with potentially enhanced responses to opicinumab.
Disclosure: Supported by: Biogen (Cambridge, MA, USA). Writing and editorial support for the preparation of this abstract was provided by Excel Scientific Solutions (Southport, CT, USA): funding was provided by Biogen.
B. Zhu, P. Wolstencroft, K. Johnson, S. Liu, I. Chang, A. Deykin, and S. Sheikh are employees of and hold stock/stock options in Biogen.
P. A. Calabresi has received consulting fees from Biogen and Disarm Therapeutics; is associate editor of The Journal of Clinical Investigation; and has received research support/grants to his institution from Annexon Biosciences, Biogen, MedImmune, Novartis and Sanofi.
G. Giovannoni is on advisory boards for AbbVie Biotherapeutics Inc., Almirall, Atara Biotherapeutics, Biogen, Merck, Merck Serono, Novartis, Roche, Sanofi-Genzyme and Teva; has received speaker fees from AbbVie Biotherapeutics Inc., Biogen, Genzyme, Merck, Merck Serono, Sanofi-Genzyme and Teva; is co-editor in chief of Multiple Sclerosis and Related Disorders; and has received research support unrelated to study from Biogen, Genzyme and Novartis.
R. Kapoor has received personal fees and/or travel support from Biogen, Genzyme and Roche; and is on clinical trial steering committees for Biogen.
R. Naismith has received consulting/speaker fees from Acorda, Alkermes, Biogen, EMD Serono, Genentech, Genzyme, Novartis and Teva.
H-P. Hartung has received speaker fees/travel expense reimbursement from and is on steering committees/advisory boards for Biogen, Geneuro, Genzyme, Merck, Medimmune, Novartis, Octapharma, Opexa, Receptos, Roche, Sanofi-Aventis and Teva.
D. L. Arnold has received personal fees for consulting from Acorda, Biogen, Hoffman La Roche, MedImmune, Mitsubishi, Novartis, Receptos, and Sanofi-Aventis; equity interest in NeuroRx Research; and grants from Biogen and Novartis.