inebilizumab (Rx)

>10%

Urinary tract infection (11%)

1-10%

Arthralgia (10%)

Infusion-related reaction, first dose (9.3%)

Headache (8%)

Back pain (7%)

Decreased neutrophils, 1-1.5 x10⁹/L (6.9%)

Contraindications

History of life-threatening infusion reaction to inebilizumab

Active HBV infection

Active or untreated latent TB

Cautions

Progressive and prolonged hypogammaglobulinemia may occur; monitor levels of quantitative serum immunoglobulins during treatment and until B-cell repletion after discontinuation of therapy, especially in patients with opportunistic or recurrent infections; consider discontinuing if low IgG or IgM develops or a serious infection

Based on animal data, can cause fetal harm owing to B-cell lymphopenia

Infusion reactions

• Can cause infusion reactions, which can include headache, nausea, somnolence, dyspnea, fever, myalgia, rash, or other signs or symptoms
• Reactions are most common with initial infusion, but were also observed during subsequent infusions
• Premedication with IV corticosteroid, antihistamine, and antipyretic required before every infusion
• For life-threatening infusion reactions, immediately and permanently discontinue and administer appropriate supportive treatment
• For less severe infusion reactions, management may involve temporarily stopping infusion, reducing infusion rate, and/or administering symptomatic treatment

Infections

• Increased risk infections observed with other B-cell-depleting therapies
• Risks include additive effects if coadministered with other immunosuppressants, HBV reactivation, progressive multifocal leukoencephalopathy, TB reactivation, or risk from live virus administration

Drug interaction overview

• Immunosuppressive drugs

  • Coadministration with immunosuppressant drugs, including systemic corticosteroids, may increase risk of infection

• Vaccines

  • Administer all needed vaccines at least 4 weeks before initiating inebilizumab
  • Vaccination with live-attenuated or live vaccines is not recommended during treatment and until B-cell repletion

• Vaccination of infants born to mothers treated during pregnancy

  • Do not administer live or live-attenuated vaccines before confirming recovery of B-cell counts in the infant
  • Depletion of B cells in these exposed infants may increase the risks from live or live-attenuated vaccines
  • Nonlive vaccines, as indicated, may be administered before recovery from B-cell and immunoglobulin level depletion; consider consultation with a qualified specialist to assess whether a protective immune response was mounted

Pregnancy

Humanized IgG1 monoclonal antibody and immunoglobulins are known to cross the placental barrier

Data are not available on developmental risk associated with use in pregnant females; however, transient peripheral B-cell depletion and lymphocytopenia have been reported in infants born to mothers exposed to other B-cell depleting antibodies during pregnancy

The potential duration of B-cell depletion in such infants, and the impact of B-cell depletion on vaccine safety and effectiveness, is unknown

Contraception

• Females of childbearing potential should use contraception during therapy and for 6 months after the last infusion

Animal data

• Administration to mice q3days throughout organogenesis and lactation resulted in depletion of B cells and persistent reductions in immune function (even following repletion of B cells and lasting into adulthood) in offspring

Lactation

Data are not available on presence in human milk, effects on breastfed infants, or on milk production

Human IgG is excreted in human milk, and the potential for absorption of inebilizumab to lead to B-cell depletion in the breastfed infant is unknown

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Monoclonal antibody that binds with high affinity to CD19, a protein expressed on a broad range of B cells, including antibody-secreting plasmablasts and plasma cells; after binding to CD19, these cells are rapidly depleted from circulation

In NMOSD, ~80% of patients have autoantibodies to a water channel protein called aquaporin-4 (AQP4); these AQP4-IgG autoantibodies are produced by plasmablasts and plasma cells and bind primarily to astrocytes in the central nervous system; binding of AQP4-IgG antibodies to CNS cells is believed to trigger attacks, which can damage the optic nerve, spinal cord, and brain

Absorption

Peak plasma concentration: 108 mcg/mL (second dose on Day 15)

AUC: 2980 mcg⋅d/mL

Distribution

Vd: 2.95 L (central); 2.57 L (peripheral)

Metabolism

Degraded by proteolytic enzymes widely distributed in the body

Elimination

Half-life: 18 days

Clearance: 0.19 L/day

IV Compatibilities

0.9% NaCl

IV Preparation

Must be diluted before administration

Before starting IV infusion, prepared infusion solution should be at room temperature

Visually inspect solution for particulate matter and discoloration; solution should appear clear to slightly opalescent, colorless to slightly yellow

If solution is cloudy, discolored, or contains discrete particulate matter, do not use and contact the manufacturer (productsafety@vielabio.com)

Do not shake vial

Withdraw 10 mL inebilizumab from each of the 3 vials contained in the carton and transfer a total of 30 mL into a 250-mL IV bag of 0.9% NaCl

Do not use other diluents to dilute

Mix diluted solution by gentle inversion; do not shake

Discard unused portion remaining in vials

IV Administration

Assess for active infection; if present, delay inebilizumab infusion until infection resolves

Administer premedications starting 30-60 minutes before inebilizumab infusion

Administer prepared inebilizumab solution IV via infusion pump at an increasing rate to completion, ~90 minutes

Close supervision by healthcare profession with access to appropriate emergency treatment is needed to manage potential reactions (eg, serious infusion reaction)

Administer through an IV line containing a sterile, low-protein–binding (0.2 or 0.22 micron) in-line filter

Monitor closely for infusion reactions during and for at least 1 hr after infusion completed

Infusion rate recommendations

• 0-30 minutes: 42 mL/hr
• 31-60 minutes: 125 mL/hr
• 61 minutes to completion: 333 mL/hr

Storage

Contains no preservative

Unopened vial

• Refrigerate at 2-8ºC (36-46ºF) in original carton to protect from light
• Do not freeze
• Do not shake
• Store vials upright

Diluted solution for infusion

• Refrigerate at 2-8ºC (36-46ºF) for up to 24 hr or at room temperature at 20-25ºC (68-77ºF) for up to 4 hr prior to starting infusion