CD20-directed Cytolytic Antibody

Briumvi

Approved 28 Dec 2022IntravenousInjectable

Indications

BRIUMVI is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults. BRIUMVI is a CD20-directed cytolytic antibody indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults ( 1 , 14 ).

Contraindications

BRIUMVI is contraindicated in patients with: Active HBV infection [see Dosage and Administration (2.1) and Warnings and Precautions (5.2) ] A history of life-threatening infusion reaction to BRIUMVI [see Warnings and Precautions (5.1) ] Active hepatitis B virus infection ( 4 ) History of life-threatening infusion reaction to BRIUMVI ( 4 )

Warnings and precautions

Infusion Reactions : Management recommendations for infusion reactions depend on the type and severity of the reaction. Permanently discontinue BRIUMVI if a life-threatening or disabling infusion reaction occurs ( 2.3 , 5.1 ). Infections : Serious, including life-threatening and fatal infections, have occurred. Delay BRIUMVI administration in patients with an active infection until the infection is resolved. Vaccination with live-attenuated or live vaccines is not recommended during treatment with BRIUMVI and after discontinuation, until B-cell repletion ( 5.2 ).

Reduction in Immunoglobulins : Monitor the level of immunoglobulins at the beginning, during, and after discontinuation of treatment with BRIUMVI, until B-cell repletion, and especially when recurrent serious infections are suspected. Consider discontinuing BRIUMVI in patients with serious opportunistic or recurrent serious infections, and if prolonged hypogammaglobulinemia requires treatment with intravenous immunoglobulins ( 2.1 , 5.4 ).

Fetal Risk : May cause fetal harm based on animal data. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for at least 6 months after stopping BRIUMVI ( 5.3 , 8.1 , 8.3 ). Liver Injury : Clinically significant liver injury has occurred. Obtain serum aminotransferases, alkaline phosphatase, and bilirubin levels before initiating BRIUMVI, and during treatment as clinically indicated.

Indications

Contraindications

Warnings and precautions

Pregnancy and breastfeeding

8.1Pregnancy Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to BRIUMVI during pregnancy. Eligible patients are women who become pregnant either while taking BRIUMVI or within 6 months following their last dose of BRIUMVI. Physicians are encouraged to register patients and pregnant women are encouraged to register themselves by calling 1-877-411-4546 or visiting www.briumvipregnancyregistry.com.

Risk Summary There are no data on the developmental risk associated with the use of BRIUMVI in pregnant women. Data from case reports of pregnancies occurring during clinical trials with BRIUMVI are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Although there are no data on ublituximab-xiiy, monoclonal antibodies can be actively transported across the placenta, and BRIUMVI may cause immunosuppression in the in-utero exposed infant [see Clinical Considerations , Warnings and Precautions (5.2 , 5.3) , and Clinical Pharmacology (12.1 , 12.2) ].

In pregnant transgenic huCD20 mice, a pharmacologically relevant animal model, weekly intravenous administration of ublituximab-xiiy during organogenesis resulted in no adverse pregnancy or embryofetal outcomes (see Data ) . The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Fetal/Neonatal Adverse Reactions Transport of endogenous IgG antibodies across the placenta increases as pregnancy progresses and peaks during the third trimester. There are no data on B-cell levels in human neonates following maternal exposure to BRIUMVI.

However, transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other anti-CD20 antibodies during pregnancy. Avoid administering live vaccines to neonates and infants exposed to BRIUMVI in utero until B-cell recovery occurs [see Warnings and Precautions (5.2) and Clinical Pharmacology (12.2) ]. Data Animal Data Weekly intravenous administration of ublituximab-xiiy (0 or 30 mg/kg) to pregnant monkeys during the first, second, or third trimester of pregnancy produced a severe immunogenic response in dams, resulting in maternal morbidity and death and embryofetal loss.

Dosing was terminated in dams after only two doses during the third trimester because of multiple deaths in dams dosed during the first and second trimesters. External, visceral, and skeletal abnormalities occurred in two infants from dams exposed during the second trimester of pregnancy. Histopathology evaluations revealed minimal to moderate degeneration/necrosis in the brain. Findings in infants included contractures and abnormal flexion of multiple limbs and tail, shortened mandible, elongate calvarium, enlargement of ears, and/or craniomandibular abnormalities which were attributed to brain necrosis.

The findings in cynomolgus monkey were considered secondary to an immunogenic reaction and are not considered relevant to humans. In a subsequent study conducted in pregnant CD20 (huCD20) transgenic mice, a pharmacologically relevant animal model, intravenous administration of ublituximab-xiiy (0, 5, 20, or 50 mg/kg) during organogenesis (gestation day 6 and 12) resulted in no adverse effects on embryofetal development.

There was a marked reduction in B-cells in fetal blood at all but the lowest dose tested.

Adverse reactions

The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Infusion Reactions [see Warnings and Precautions (5.1) ] Infections [see Warnings and Precautions (5.2) ] Reduction in Immunoglobulins [see Warnings and Precautions (5.4) ] Liver Injury [see Warnings and Precautions (5.5) ] The most common adverse reactions (≥10%) were infusion reactions and upper respiratory tract infections ( 6.1 ).

To report SUSPECTED ADVERSE REACTIONS, contact TG Therapeutics at 1-877-848-9462 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. In active-controlled clinical trials (Study 1 and Study 2), 545 patients with RMS received BRIUMVI [see Clinical Studies (14) ]. The most common adverse reactions in RMS trials (incidence of at least 10%) were infusion reactions and upper respiratory tract infections.

Table 2 summarizes the adverse reactions that occurred in RMS trials (Study 1 and Study 2). The most common cause of discontinuation in patients treated with BRIUMVI was infection (1.3%). Table 2: Adverse Reactions in Adult Patients with RMS with an Incidence of at least 5% for BRIUMVI and Higher than Teriflunomide from Study 1 and Study 2 BRIUMVI 450 mg IV The first dose of BRIUMVI was given as an intravenous (IV) infusion of 150 mg.

The second dose was given as an IV infusion of 450 mg two weeks after the first infusion. Teriflunomide 14 mg PO Adverse Reactions (N=545) % (N=548) % Infusion reactions 48 12 Upper respiratory tract infections Includes the following: nasopharyngitis, upper respiratory tract infection, respiratory tract infection, respiratory tract infection viral, pharyngitis, rhinitis, sinusitis, acute sinusitis, tonsillitis, laryngitis, chronic sinusitis, viral pharyngitis, viral rhinitis, viral upper respiratory tract infection, chronic tonsillitis, pharyngitis streptococcal, sinusitis bacterial, and tonsillitis bacterial. 45 41 Lower respiratory tract infections Includes the following: bronchitis, pneumonia, tracheitis, tracheobronchitis, COVID-19 pneumonia, bronchitis bacterial, and pneumonia viral. 9 7 Herpes virus-associated infections Includes several related terms. 6 5 Pain in extremity 6 4 Insomnia 6 3 Fatigue 5 4 Infusion Reactions The incidence of infusion reactions was highest with the first infusion (43%), decreasing with subsequent infusions (10% with second, 8% with third infusion).

Three (0.6%) patients treated with BRIUMVI reported serious infusion reactions. Most frequently reported symptoms (greater than 5%) included pyrexia, chills, headache, and influenza-like illness [see Warnings and Precautions (5.1) ] . Laboratory Abnormalities Decreased Immunoglobulins BRIUMVI decreased total immunoglobulins with the greatest decline seen in IgM levels. The proportion of BRIUMVI-treated patients at baseline reporting IgG, IgA, and IgM below the LLN was 6.3%, 0.6%, and 1.1%, respectively.

Following treatment, the proportion of BRIUMVI-treated patients reporting IgG, IgA, and IgM below the LLN at 96 weeks was 6.5%, 2.4%, and 20.9%, respectively. Decreased Neutrophil Levels In Studies 1 and 2, decreased neutrophil counts (<LLN) occurred in 15% of BRIUMVI-treated patients compared to 22% in teriflunomide-treated patients. The majority of decreased neutrophil counts were observed once for a given patient treated with BRIUMVI, and were between 1.0 and 1.5 × 10 9 /L.

In RMS studies, 3% of patients in the BRIUMVI group had neutrophil counts less than 1.0 × 10 9 /L, compared to 2% of patients in the teriflunomide group. Overall, 1% of patients in the BRIUMVI group had neutrophil counts less than 0.5 × 10 9 /L, compared to 0% of patients in the teriflunomide group, and these were not associated with an infection.

6.2Postmarketing Experience

The following adverse reactions have been identified during postapproval use of BRIUMVI. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hepatobiliary Disorders: Liver injury [see Warnings and Precautions (5.5) ] Infections and Infestations: Progressive multifocal leukoencephalopathy [see Warnings and Precautions (5.2) ]

Briumvi

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

Briumvi

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

5.1Infusion Reactions

5.2Infections

Interactions

7.1Immunosuppressive or Immune-Modulating Therapies

Pregnancy and breastfeeding

8.1Pregnancy Pregnancy Exposure Registry

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Official product information

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