BRIUMVI
Generic: UBLITUXIMAB
Basic Information
Manufacturer
TG Therapeutics, Inc.
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
INTRAVENOUS
FDA Set ID
3a77cd8c-811b-407c-9140-d0c5c26435c2
Indications & Usage
1 INDICATIONS AND USAGE 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 ).
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 ).
Adverse Reactions
6 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.
6.1 Clinical 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.
6.2 Postmarketing 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) ]
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.
6.1 Clinical 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.
6.2 Postmarketing 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) ]