Positive Phase 3 Results Support Simplified Ublituximab-xiiy Dosing for Relapsing MS

TG Therapeutics has announced successful topline results from its phase 3 ENHANCE trial, potentially transforming the initiation protocol for ublituximab-xiiy (Briumvi). The trial demonstrated that a consolidated single-infusion regimen for starting therapy is bioequivalent to the currently approved multi-day schedule, a development that promises to streamline operations for pharmacists and infusion centers alike.¹

The Data: Bioequivalence and Enhanced Safety

The ENHANCE trial was a randomized, double-blind study designed to compare the pharmacokinetics and safety of a single 600 mg infusion on day 1 against the currently approved regimen of 150 mg on day 1 followed by 450 mg on day 15.^1,2 The study met its primary end point, with the total drug exposure (AUC 0-Wk16) proving nearly identical between the 2 arms. The geometric mean ratio was approximately 1.0, falling strictly within the predefined bioequivalence range.¹

For clinical pharmacists monitoring safety profiles, the results were equally encouraging. Secondary end points, including B-cell depletion and MRI outcomes, remained consistent with previous ublituximab-xiiy studies. Notably, infusion-related reactions (IRRs) were statistically indistinguishable between the 2 groups, with the consolidated single-infusion arm actually reporting fewer reactions than the split-dose arm. Furthermore, no grade 3 or higher IRRs occurred in either group during the trial.¹

Relevance for Pharmacists and Infusion Centers

The shift toward a single-infusion initiation carries significant implications for pharmacy practice and health care delivery. Currently, the 2-visit initiation requirement can create logistical hurdles such as scheduling burdens at busy facilities, a complex compounding and dispensing process, and slower time to treatment.

In a news release, TG Therapeutics Chairman and CEO Michael S. Weiss said, “By eliminating the need for a second infusion visit 2 weeks after treatment initiation, this streamlined dosing regimen has the potential to accelerate time from prescription to treatment and reduce scheduling burdens at busy infusion centers. If this consolidated dosing is approved, Briumvi would be the first and only [intravenous] anti-CD20 for which therapy can be initiated with a single infusion.”¹

Clinical Background: The Glycoengineering Advantage

Ublituximab-xiiy is a novel monoclonal antibody targeting a unique epitope in on CD20-expressing B-cells. Its distinctiveness lies in its glycoengineering process, which involves the removal of specific sugar molecules from the antibody. This modification is designed to allow for efficient B-cell depletion even at lower doses.¹

Pharmacists should remain mindful of the established safety profile. Although the ENHANCE data showed no new signals, ublituximab-xiiy remains associated with risks common to anti-CD20 therapies, including infusion reactions, infections, and hepatitis B virus (HBV) reactivation. Screening for HBV and monitoring for signs of progressive multifocal leukoencephalopathy remain standard requirements before and during treatment.¹

Looking Ahead

With the successful completion of the ENHANCE trial, TG Therapeutics plans to submit a supplemental Biologics License Application to the FDA in the second half of 2026. If approved, ublituximab-xiiy would become the first and only intravenous anti-CD20 therapy for relapsing multiple sclerosis that can be initiated with a single infusion. For pharmacists, this represents a significant step toward treatment simplicity in a complex disease state where patient adherence and facility efficiency are paramount.

REFERENCES
1. TG Therapeutics Announces Positive Topline Results from Phase 3 ENHANCE trial. News release. TG Therapeutics. May 27, 2026. Accessed May 27, 2026. https://ir.tgtherapeutics.com/news-releases/news-release-details/tg-therapeutics-announces-positive-topline-results-phase-3

2. TG Therapeutics completes enrollment in the phase 3 ENHANCE trial evaluating its new simplified dosing schedule for Briumvi. News release. TG Therapeutics. October 28, 2025. Accessed May 27, 2026. https://ir.tgtherapeutics.com/news-releases/news-release-details/tg-therapeutics-completes-enrollment-phase-3-enhance-trial