A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis

Ublituximab, a novel monoclonal antibody (mAb) targeting a unique epitope on the CD20 antigen, is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity (ADCC). Greater ADCC may allow lower doses and shorter infusion times versus other anti-CD20 mAbs. The obje...

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Vydáno v:	Multiple sclerosis Ročník 27; číslo 3; s. 420
Hlavní autoři:	Fox, Edward, Lovett-Racke, Amy E, Gormley, Matthew, Liu, Yue, Petracca, Maria, Cocozza, Sirio, Shubin, Richard, Wray, Sibyl, Weiss, Michael S, Bosco, Jenna A, Power, Sean A, Mok, Koby, Inglese, Matilde
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England 01.03.2021
Témata:	gadolinium-enhancing lesions magnetic resonance imaging relapse multiple sclerosis TG-1101 Ublituximab
ISSN:	1477-0970, 1477-0970
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Abstract	Ublituximab, a novel monoclonal antibody (mAb) targeting a unique epitope on the CD20 antigen, is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity (ADCC). Greater ADCC may allow lower doses and shorter infusion times versus other anti-CD20 mAbs. The objective was to determine optimal dose, infusion time, and activity of ublituximab in relapsing multiple sclerosis. This is a phase 2, placebo-controlled study. Patients received three ublituximab infusions (150 mg over 1-4 hours on day 1 and 450-600 mg over 1-3 hours on day 15 and week 24) in six dosing cohorts. The primary endpoint was B-cell depletion. In all cohorts ( = 48), median B-cell depletion was >99% by week 4, maintained at weeks 24 and 48. Most common adverse events (AEs) were infusion-related reactions (all grade 1-2), with no apparent increased incidence at shorter infusion times. There were no AE-related discontinuations. At weeks 24 and 48, no T1 gadolinium-enhancing lesions ( = 0.003) and a 10.6% decrease in T2 lesion volume ( = 0.002) were detected. The annualized relapse rate was 0.07; 93% remained relapse free on study. Overall, 74% of patients had no evidence of disease activity (NEDA). Ublituximab was safely infused as rapid as 1 hour, producing robust B-cell depletion and profound reductions in magnetic resonance imaging (MRI) activity and relapses.
AbstractList	Ublituximab, a novel monoclonal antibody (mAb) targeting a unique epitope on the CD20 antigen, is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity (ADCC). Greater ADCC may allow lower doses and shorter infusion times versus other anti-CD20 mAbs.BACKGROUNDUblituximab, a novel monoclonal antibody (mAb) targeting a unique epitope on the CD20 antigen, is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity (ADCC). Greater ADCC may allow lower doses and shorter infusion times versus other anti-CD20 mAbs.The objective was to determine optimal dose, infusion time, and activity of ublituximab in relapsing multiple sclerosis.OBJECTIVEThe objective was to determine optimal dose, infusion time, and activity of ublituximab in relapsing multiple sclerosis.This is a phase 2, placebo-controlled study. Patients received three ublituximab infusions (150 mg over 1-4 hours on day 1 and 450-600 mg over 1-3 hours on day 15 and week 24) in six dosing cohorts. The primary endpoint was B-cell depletion.METHODSThis is a phase 2, placebo-controlled study. Patients received three ublituximab infusions (150 mg over 1-4 hours on day 1 and 450-600 mg over 1-3 hours on day 15 and week 24) in six dosing cohorts. The primary endpoint was B-cell depletion.In all cohorts (N = 48), median B-cell depletion was >99% by week 4, maintained at weeks 24 and 48. Most common adverse events (AEs) were infusion-related reactions (all grade 1-2), with no apparent increased incidence at shorter infusion times. There were no AE-related discontinuations. At weeks 24 and 48, no T1 gadolinium-enhancing lesions (p = 0.003) and a 10.6% decrease in T2 lesion volume (p = 0.002) were detected. The annualized relapse rate was 0.07; 93% remained relapse free on study. Overall, 74% of patients had no evidence of disease activity (NEDA).RESULTSIn all cohorts (N = 48), median B-cell depletion was >99% by week 4, maintained at weeks 24 and 48. Most common adverse events (AEs) were infusion-related reactions (all grade 1-2), with no apparent increased incidence at shorter infusion times. There were no AE-related discontinuations. At weeks 24 and 48, no T1 gadolinium-enhancing lesions (p = 0.003) and a 10.6% decrease in T2 lesion volume (p = 0.002) were detected. The annualized relapse rate was 0.07; 93% remained relapse free on study. Overall, 74% of patients had no evidence of disease activity (NEDA).Ublituximab was safely infused as rapid as 1 hour, producing robust B-cell depletion and profound reductions in magnetic resonance imaging (MRI) activity and relapses.CONCLUSIONUblituximab was safely infused as rapid as 1 hour, producing robust B-cell depletion and profound reductions in magnetic resonance imaging (MRI) activity and relapses. Ublituximab, a novel monoclonal antibody (mAb) targeting a unique epitope on the CD20 antigen, is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity (ADCC). Greater ADCC may allow lower doses and shorter infusion times versus other anti-CD20 mAbs. The objective was to determine optimal dose, infusion time, and activity of ublituximab in relapsing multiple sclerosis. This is a phase 2, placebo-controlled study. Patients received three ublituximab infusions (150 mg over 1-4 hours on day 1 and 450-600 mg over 1-3 hours on day 15 and week 24) in six dosing cohorts. The primary endpoint was B-cell depletion. In all cohorts ( = 48), median B-cell depletion was >99% by week 4, maintained at weeks 24 and 48. Most common adverse events (AEs) were infusion-related reactions (all grade 1-2), with no apparent increased incidence at shorter infusion times. There were no AE-related discontinuations. At weeks 24 and 48, no T1 gadolinium-enhancing lesions ( = 0.003) and a 10.6% decrease in T2 lesion volume ( = 0.002) were detected. The annualized relapse rate was 0.07; 93% remained relapse free on study. Overall, 74% of patients had no evidence of disease activity (NEDA). Ublituximab was safely infused as rapid as 1 hour, producing robust B-cell depletion and profound reductions in magnetic resonance imaging (MRI) activity and relapses.
Author	Wray, Sibyl Bosco, Jenna A Shubin, Richard Power, Sean A Cocozza, Sirio Weiss, Michael S Inglese, Matilde Petracca, Maria Lovett-Racke, Amy E Mok, Koby Liu, Yue Fox, Edward Gormley, Matthew
Author_xml	– sequence: 1 givenname: Edward surname: Fox fullname: Fox, Edward organization: Central Texas Neurology Consultants, Round Rock, TX, USA – sequence: 2 givenname: Amy E surname: Lovett-Racke fullname: Lovett-Racke, Amy E organization: Department of Microbial Infection and Immunity, The Ohio State University Wexner Medical Center, Columbus, OH, USA – sequence: 3 givenname: Matthew surname: Gormley fullname: Gormley, Matthew organization: Department of Microbial Infection and Immunity, The Ohio State University Wexner Medical Center, Columbus, OH, USA – sequence: 4 givenname: Yue surname: Liu fullname: Liu, Yue organization: Department of Microbial Infection and Immunity, The Ohio State University Wexner Medical Center, Columbus, OH, USA – sequence: 5 givenname: Maria surname: Petracca fullname: Petracca, Maria organization: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA – sequence: 6 givenname: Sirio surname: Cocozza fullname: Cocozza, Sirio organization: Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA/Department of Advanced Biomedical Sciences, University of Naples Federico II, Naples, Italy – sequence: 7 givenname: Richard surname: Shubin fullname: Shubin, Richard organization: SC3 Research Group, Inc., Pasadena, CA, USA – sequence: 8 givenname: Sibyl surname: Wray fullname: Wray, Sibyl organization: Hope Neurology Multiple Sclerosis Center, Knoxville, TN, USA – sequence: 9 givenname: Michael S surname: Weiss fullname: Weiss, Michael S organization: TG Therapeutics, Inc., New York, NY, USA – sequence: 10 givenname: Jenna A surname: Bosco fullname: Bosco, Jenna A organization: TG Therapeutics, Inc., New York, NY, USA – sequence: 11 givenname: Sean A surname: Power fullname: Power, Sean A organization: TG Therapeutics, Inc., New York, NY, USA – sequence: 12 givenname: Koby surname: Mok fullname: Mok, Koby organization: TG Therapeutics, Inc., New York, NY, USA – sequence: 13 givenname: Matilde surname: Inglese fullname: Inglese, Matilde organization: Medical Center, Department of Neurology, Radiology and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Title	A phase 2 multicenter study of ublituximab, a novel glycoengineered anti-CD20 monoclonal antibody, in patients with relapsing forms of multiple sclerosis
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