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Ublituximab, a novel anti-CD20 antibody, rapidly and robustly depletes B cells in patients with relapsing forms of multiple sclerosis (MS), according to phase 2 trial results presented at ACTRIMS Forum 2019. Patients treated with the investigational therapy had reduced MRI activity and relapse rates during the 48-week trial, and the treatment was well tolerated, researchers said.

The monoclonal antibody targets a unique epitope on the CD20 antigen and is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity, said presenting author Edward Fox, MD, PhD, director of the MS Clinic of Central Texas, Round Rock. Ublituximab’s potency “may offer a benefit over currently available anti-CD20s in terms of lower doses and shorter infusion times,” Dr. Fox and his research colleagues said.

To assess the optimal dose, infusion time, safety, and tolerability of ublituximab in relapsing MS, investigators conducted a phase 2, multicenter study. The trial included 48 patients with relapsing MS; 65% were female. Patients’ average age was 40 years and average disease duration was 7.7 years. The researchers included patients with one or more confirmed relapse in the past year, two relapses in the past 2 years, or at least one active gadolinium-enhancing T1 lesion. The primary endpoint was the percentage of patients with at least a 95% reduction in peripheral CD19+ B cells within 2 weeks after the second infusion on day 15.

For their first infusions, patients received 150 mg of ublituximab over an infusion time of 1, 2, 3, or 4 hours. On day 15, patients received 450 mg or 600 mg of ublituximab over an infusion time of 1, 1.5, or 3 hours. At week 24, patients received 450 mg or 650 mg of ublituximab infused over 1 hour or 1.5 hours.

All patients met the primary endpoint of greater than 95% B-cell depletion between baseline and week 4. Median B-cell depletion was 99% at week 4, and this effect was maintained at weeks 24 and 48.

The researchers detected no T1 gadolinium-enhancing lesions at week 24 or week 48, and total T2 lesion volume decreased by 10.6% between baseline and week 48.

The most frequent adverse events were infusion-related reactions, which occurred in 48% of patients and were more common with the first infusion, particularly when the infusion time was less than 4 hours. All of the infusion-related reactions were grade 1 or 2. One grade 3 serious adverse event of fatigue was considered possibly related to ublituximab. No patients withdrew from the study because of drug-related adverse events. At week 48, 93% of the patients were relapse free, 7% had 24-week confirmed disability progression, and 17% had confirmed disability improvement.

TG Therapeutics, the company developing ublituximab, is evaluating the therapy in phase 3 trials known as ULTIMATE I and 2. The phase 3 trials are using the 450-mg dose with a first dose of 150 mg delivered over 4 hours.

Dr. Fox has disclosed research support from TG Therapeutics and other pharmaceutical companies and working as a consultant and speaker for TG Therapeutics and other companies.

jremaly@mdedge.com

SOURCE: Fox E et al. ACTRIMS Forum 2019, Abstract 66.

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Ublituximab, a novel anti-CD20 antibody, rapidly and robustly depletes B cells in patients with relapsing forms of multiple sclerosis (MS), according to phase 2 trial results presented at ACTRIMS Forum 2019. Patients treated with the investigational therapy had reduced MRI activity and relapse rates during the 48-week trial, and the treatment was well tolerated, researchers said.

The monoclonal antibody targets a unique epitope on the CD20 antigen and is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity, said presenting author Edward Fox, MD, PhD, director of the MS Clinic of Central Texas, Round Rock. Ublituximab’s potency “may offer a benefit over currently available anti-CD20s in terms of lower doses and shorter infusion times,” Dr. Fox and his research colleagues said.

To assess the optimal dose, infusion time, safety, and tolerability of ublituximab in relapsing MS, investigators conducted a phase 2, multicenter study. The trial included 48 patients with relapsing MS; 65% were female. Patients’ average age was 40 years and average disease duration was 7.7 years. The researchers included patients with one or more confirmed relapse in the past year, two relapses in the past 2 years, or at least one active gadolinium-enhancing T1 lesion. The primary endpoint was the percentage of patients with at least a 95% reduction in peripheral CD19+ B cells within 2 weeks after the second infusion on day 15.

For their first infusions, patients received 150 mg of ublituximab over an infusion time of 1, 2, 3, or 4 hours. On day 15, patients received 450 mg or 600 mg of ublituximab over an infusion time of 1, 1.5, or 3 hours. At week 24, patients received 450 mg or 650 mg of ublituximab infused over 1 hour or 1.5 hours.

All patients met the primary endpoint of greater than 95% B-cell depletion between baseline and week 4. Median B-cell depletion was 99% at week 4, and this effect was maintained at weeks 24 and 48.

The researchers detected no T1 gadolinium-enhancing lesions at week 24 or week 48, and total T2 lesion volume decreased by 10.6% between baseline and week 48.

The most frequent adverse events were infusion-related reactions, which occurred in 48% of patients and were more common with the first infusion, particularly when the infusion time was less than 4 hours. All of the infusion-related reactions were grade 1 or 2. One grade 3 serious adverse event of fatigue was considered possibly related to ublituximab. No patients withdrew from the study because of drug-related adverse events. At week 48, 93% of the patients were relapse free, 7% had 24-week confirmed disability progression, and 17% had confirmed disability improvement.

TG Therapeutics, the company developing ublituximab, is evaluating the therapy in phase 3 trials known as ULTIMATE I and 2. The phase 3 trials are using the 450-mg dose with a first dose of 150 mg delivered over 4 hours.

Dr. Fox has disclosed research support from TG Therapeutics and other pharmaceutical companies and working as a consultant and speaker for TG Therapeutics and other companies.

jremaly@mdedge.com

SOURCE: Fox E et al. ACTRIMS Forum 2019, Abstract 66.

Ublituximab, a novel anti-CD20 antibody, rapidly and robustly depletes B cells in patients with relapsing forms of multiple sclerosis (MS), according to phase 2 trial results presented at ACTRIMS Forum 2019. Patients treated with the investigational therapy had reduced MRI activity and relapse rates during the 48-week trial, and the treatment was well tolerated, researchers said.

The monoclonal antibody targets a unique epitope on the CD20 antigen and is glycoengineered for enhanced B-cell targeting through antibody-dependent cellular cytotoxicity, said presenting author Edward Fox, MD, PhD, director of the MS Clinic of Central Texas, Round Rock. Ublituximab’s potency “may offer a benefit over currently available anti-CD20s in terms of lower doses and shorter infusion times,” Dr. Fox and his research colleagues said.

To assess the optimal dose, infusion time, safety, and tolerability of ublituximab in relapsing MS, investigators conducted a phase 2, multicenter study. The trial included 48 patients with relapsing MS; 65% were female. Patients’ average age was 40 years and average disease duration was 7.7 years. The researchers included patients with one or more confirmed relapse in the past year, two relapses in the past 2 years, or at least one active gadolinium-enhancing T1 lesion. The primary endpoint was the percentage of patients with at least a 95% reduction in peripheral CD19+ B cells within 2 weeks after the second infusion on day 15.

For their first infusions, patients received 150 mg of ublituximab over an infusion time of 1, 2, 3, or 4 hours. On day 15, patients received 450 mg or 600 mg of ublituximab over an infusion time of 1, 1.5, or 3 hours. At week 24, patients received 450 mg or 650 mg of ublituximab infused over 1 hour or 1.5 hours.

All patients met the primary endpoint of greater than 95% B-cell depletion between baseline and week 4. Median B-cell depletion was 99% at week 4, and this effect was maintained at weeks 24 and 48.

The researchers detected no T1 gadolinium-enhancing lesions at week 24 or week 48, and total T2 lesion volume decreased by 10.6% between baseline and week 48.

The most frequent adverse events were infusion-related reactions, which occurred in 48% of patients and were more common with the first infusion, particularly when the infusion time was less than 4 hours. All of the infusion-related reactions were grade 1 or 2. One grade 3 serious adverse event of fatigue was considered possibly related to ublituximab. No patients withdrew from the study because of drug-related adverse events. At week 48, 93% of the patients were relapse free, 7% had 24-week confirmed disability progression, and 17% had confirmed disability improvement.

TG Therapeutics, the company developing ublituximab, is evaluating the therapy in phase 3 trials known as ULTIMATE I and 2. The phase 3 trials are using the 450-mg dose with a first dose of 150 mg delivered over 4 hours.

Dr. Fox has disclosed research support from TG Therapeutics and other pharmaceutical companies and working as a consultant and speaker for TG Therapeutics and other companies.

jremaly@mdedge.com

SOURCE: Fox E et al. ACTRIMS Forum 2019, Abstract 66.

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REPORTING FROM ACTRIMS FORUM 2019

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