FDA Approves Briumvi™ for the Treatment of Relapsing Forms of MS
Reviewed by MSAA Chief Medical Officer Barry A. Hendin, MD
TG Therapeutics has announced that the United States Food and Drug Administration (FDA) approved Briumvi™ (ublituximab-xiiy) for the treatment of relapsing forms of multiple sclerosis (MS) in adults – including clinically isolated syndrome, relapsing-remitting MS, and active secondary-progressive MS. This medication is a monoclonal antibody that targets CD20, a protein found on the surface of B cells, and induces B-cell depletion within 24 hours. B cells are white blood cells shown to play a role in MS.
Briumvi is given by infusion, with two initial doses administered 14 days apart, followed by infusions every 24 weeks. In studies, Briumvi met its primary end point of reducing annualized relapse rates when compared to individuals taking the oral medication, Aubagio® (teriflunomide). It also met certain secondary endpoints, including the reduction of gadolinium-enhancing lesions as seen on magnetic resonance imaging (MRI), compared to individuals taking Aubagio.
The most common side effect was infusion-related reactions. This new therapy is expected to be available in early 2023.
Study Design and Findings
The Phase III ULTIMATE I and ULTIMATE II trials were identical, double-blind, and double-dummy (placebo) studies taking place at 104 sites throughout 10 countries. Enrolled participants were between the ages of 18 and 55, were diagnosed with relapsing MS, were limited to the use and timing of certain disease-modifying treatments, and had an Expanded Disability Status Scale (EDSS) score of 0 to 5.5 (with greater scores indicating more significant disability).
Between September 2017 and October 2018, the ULTIMATE I trial enrolled 549 individuals and the ULTIMATE II trial enrolled 545. Participants were randomized and the numbers were split in half to receive either Briumvi with an oral placebo or Aubagio with an intravenous placebo. The median follow-up of these studies was 95 weeks (a little less than two years) and some of the results were determined through a pooled analysis of both trials.
Results of these two studies include the following:
- In the ULTIMATE I trial, the annualized relapse rate was 0.08 in the Briumvi group versus 0.19 in the Aubagio group. In the ULTIMATE II trial, the annualized relapse rate was 0.09 and 0.18, respectively. Generally speaking, individuals taking Briumvi experienced about half the relapses than those taking Aubagio.
- In the ULTIMATE I trial, the mean number of gadolinium-enhancing lesions (per T1-weighted MRI scan) was 0.02 in the Briumvi group versus 0.49 in the Aubagio group. In the ULTIMATE II trial, the mean number of gadolinium-enhancing lesions was 0.01 and 0.25, respectively.
- In the ULTIMATE I trial, the mean number of new or enlarging hypointense lesions (per T2-weighted MRI scan) was 0.21 in the Briumvi group versus 2.79 in the Aubagio group. In the ULTIMATE II trial, the mean number of new or enlarging hypointense lesions was 0.28 and 2.83, respectively.
- In the ULTIMATE I trial, “no evidence of disease activity” (NEDA) was seen in 44.6% of those treated with Briumvi versus 15.0% of those receiving Aubagio. In the ULTIMATE II trial, NEDA was seen in 43.0% of those treated with Briumvi versus 11.4% of those receiving Aubagio.
Side Effects, Adverse Events, and Screenings Required
Among those taking Briumvi, the most common adverse event was infusion-related reactions (47.7%). Fever, headache, chills, and flu-like symptoms were the most commonly reported symptoms when experiencing an infusion-related reaction. Other side effects included headache (34.3%), nasopharyngitis [cold symptoms] (18.3%), pyrexia [fever] (13.9%), and nausea (10.6%). These were compared to side effects experienced by the Aubagio group, whose most common adverse events included headache (26.6%), nasopharyngitis (17.9%), alopecia [hair loss] (15.3%), infusion-related reactions [to the placebo given intravenously] (12.2%), and diarrhea (10.6%).
Looking at both trials combined, just over half of each treatment group experienced infections – 304 participants or 55.8% of the Briumvi group and 298 or 54.4% of the Aubagio group. Most of these were related to the respiratory tract. Urinary tract infections and herpes virus infections also were seen in smaller percentages of participants.
Serious and life-threatening infections were seen in 5% of study participants taking Briumvi, compared to 3% of those taking Aubagio. Three infection-related deaths occurred with Briumvi-treated patients. Administration of Briumvi should be delayed in patients experiencing active infection.
Also in these trials, one participant taking Briumvi experienced Hepatitis B Virus (HBV) reactivation. All patients should be screened for HBV prior to starting Briumvi and anyone with active HBV should not be given Briumvi.
Although cases of progressive multifocal leukoencephalopathy (PML) have been reported in patients taking other anti-CD20 antibodies, no cases of PML occurred during the 96-week period. Additionally, no opportunistic infections were reported.
Results of animal studies suggest that Briumvi may harm the fetus if given to a pregnant woman. For this reason, women who could become pregnant should be given a pregnancy test prior to starting Briumvi as well as prior to each infusion. Effective contraception is recommended during treatment with Briumvi and for six months after discontinuing treatment.
For More Information
For more information, please visit www.briumvi.com, or go to TG Therapeutics’ dedicated patient support website at www.briumvipatientsupport.com. This latter website will be available to access within a few days following this approval. Interested individuals may also call 1-833-BRIUMVI, or 1-833-274-8684.
Whether connecting online or via phone, patient support representatives can provide information about financial assistance programs. Representatives can also assist individuals with locating their nearest infusion site. As noted earlier, Briumvi is expected to be available in early 2023.
For general information or to speak with one of MSAA’s trained Client Services Specialists, please contact us in one of the following ways:
- Call (800) 532-7667, extension 154 or email MSquestions@mymsaa.org. Helpline hours are Monday through Friday, 8:30 AM to 8:00 PM, Eastern Time. To reach a Spanish-speaking Client Services Specialist, please call (800) 532-7667, extension 131.
- Para comunicarse con un Especialista de Servicios al Cliente que habla español, llame al (800) 532-7667, extensión 131 o envíe un correo electrónico a MSquestions@mymsaa.org. El horario de la línea de ayuda es de lunes a viernes, de 8:30 AM a 8:00 PM, hora del este.