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Phase III trials were randomized, double-blind, and placebo-controlled, and assessed intravenous and subcutaneous methods of administration1-4

BLISS-SC
Patients enrolled: N=836
Treatments: BENLYSTA SC 200 mg + standard therapy vs placebo + standard therapy
Duration: 52 weeks
Regions: 177 centers throughout North America, South America, Europe and Asia
BLISS-52
Patients enrolled: N=865
Treatments: BENLYSTA IV 1 mg/kg*, BENLYSTA IV 10 mg/kg, or placebo, each in addition to standard therapy
Duration: 52 weeks
Region: 90 centers throughout South America, Asia, Eastern Europe and Australia
BLISS-76
Patients enrolled: N=819
Treatments: BENLYSTA IV 1 mg/kg*, BENLYSTA IV 10 mg/kg, or placebo, each in addition to standard therapy
Duration: 76 weeks with primary endpoint at 52 weeks
Regions: 136 centers throughout North America and Europe

*The 1-mg/kg dose is not recommended.

ENTRY CRITERIA

Phase III trial entry criteria

STANDARD THERAPIES PERMITTED

Permitted changes to standard therapy2-5

  • No new NSAID was permitted after Week 44, unless the duration of treatment was <1 week
  • Patients dropping out of the trial early, or requiring changes in standard therapy that were not permitted, were considered non-responders
  • In the trial, a higher proportion of patients on placebo + standard therapy were considered failures for these reasons compared with the BENLYSTA group

SRI-4 PRIMARY ENDPOINT

*Prednisone or prednisone equivalent.
Within 8 weeks before Week 52, daily corticosteroid dose could not be increased beyond the dose at Week 44 or at baseline, whichever was higher.
At Week 24, daily corticosteroid dose (defined as sum of all corticosteroid doses over any 7 consecutive days divided by 7).
§The primary efficacy endpoint was a composite index (SLE Responder Index-4 or SRI-4) that comprised the following criteria at Week 52 vs baseline: ≥4-point reduction in SELENA-SLEDAI (Safety of Estrogens in Lupus Erythematosus: National Assessment Version of the Systemic Lupus Erythematosus Disease Activity Index) score and no new BILAG (British Isles Lupus Assessment Group) A organ domain score or 2 new BILAG B organ domain scores and no worsening (<0.30-point increase) in PGA (Physician’s Global Assessment) score.
||glucocorticoid >20 mg/day or immunosuppressants.
eg, antimalarial drugs, NSAIDs, or glucocorticoids <20 mg/day.

REFERENCES:

  1. BENLYSTA [package insert]. Research Triangle Park, NC: GlaxoSmithKline, 2018.
  2. Stohl W, Schwarting A, Okada M, et al. Efficacy and safety of subcutaneous belimumab in systemic lupus erythematosus: a fifty-two–week randomized, double-blind, placebo-controlled study. Arthritis Rheumatol. 2017;69(5):1016-1027.
  3. Navarra SV, Guzmán RM, Gallacher AE, et al. Efficacy and safety of belimumab in patients with active systemic lupus erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 2011;377(9767):721-731.
  4. Furie R, Petri M, Zamani O, et al. A phase III, randomized, placebo-controlled study of belimumab, a monoclonal antibody that inhibits B lymphocyte stimulator, in patients with systemic lupus erythematosus. Arthritis Rheum. 2011;63(12):3‍918-3930.
  5. Data on file, Human Genome Sciences, Inc.
  6. Furie RA, Petri MA, Wallace DJ, et al. Novel evidence-based systemic lupus erythematosus responder index. Arthritis Rheum. 2009;61(9):1143-1151.

Indication

BENLYSTA is indicated for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy.

Limitations of Use: The efficacy of BENLYSTA has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. BENLYSTA has not been studied in combination with other biologics or intravenous cyclophosphamide. Use of BENLYSTA is not recommended in these situations.

How supplied: BENLYSTA for intravenous use (IV) is available as 120 mg in a 5-mL single-dose vial and 400 mg in a 20-mL single-dose vial. BENLYSTA for subcutaneous use (SC) is available as 200 mg in a 1-mL single-dose prefilled autoinjector and 200 mg in a 1-mL single-dose prefilled glass syringe.

Important Safety Information

CONTRAINDICATION

Previous anaphylaxis with BENLYSTA.

WARNINGS AND PRECAUTIONS

MORTALITY

In controlled clinical trials, death occurred in 0.8% (11/1,458) of patients treated with BENLYSTA IV and in 0.4% (3/675) of patients receiving placebo. Etiologies included infection, cardiovascular disease, and suicide.

In the controlled trial (N=836), death occurred in 0.5% (3/556) of patients receiving BENLYSTA SC and 0.7% (2/280) of patients receiving placebo. Infection was the most common cause of death.

SERIOUS INFECTIONS

Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents, including BENLYSTA. The most frequent serious infections were pneumonia, including bacterial pneumonia, urinary tract infection, cellulitis, herpes zoster, and bronchitis. Use caution in patients with severe or chronic infections. Consider interrupting therapy with BENLYSTA in patients who develop a new infection.

Progressive Multifocal Leukoencephalopathy (PML): Cases of JC virus-associated PML resulting in neurological deficits, including fatal cases, have been reported in patients with SLE receiving immunosuppressants, including BENLYSTA. If PML is confirmed, consider stopping immunosuppressant therapy, including BENLYSTA.

HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS) AND INFUSION REACTIONS

Acute hypersensitivity reactions, including anaphylaxis and death, have been reported in association with infusions and injections of BENLYSTA, including in patients who have previously tolerated BENLYSTA. These events generally occurred within hours of the infusion; however, they may occur later. Non-acute hypersensitivity reactions including rash, nausea, fatigue, myalgia, headache, and facial edema, have been reported and typically occurred up to a week following the most recent infusion. Patients with a history of multiple drug allergies or significant hypersensitivity may be at increased risk. Premedication may mitigate or mask an infusion reaction or hypersensitivity response. In the controlled trial of BENLYSTA SC, systemic hypersensitivity reactions were similar to those observed in the IV clinical trials. Anaphylaxis was observed in 0.6% and 0.4% of patients receiving BENLYSTA and placebo, respectively. Manifestations included hypotension, angioedema, urticaria or other rash, pruritus, and dyspnea.

Serious infusion reactions (excluding hypersensitivity reactions) were reported in 0.5% and 0.4% of patients receiving BENLYSTA and placebo, respectively and included bradycardia, myalgia, headache, rash, urticaria, and hypotension. BENLYSTA IV should be administered by healthcare providers prepared to manage infusion reactions and anaphylaxis. The infusion rate may be slowed or interrupted if the patient develops an infusion reaction. In the event of a serious reaction, administration of BENLYSTA must be discontinued immediately and appropriate medical therapy administered. Patients should be closely monitored during and for an appropriate period of time after IV administration of BENLYSTA. Patients receiving BENLYSTA should be informed of the signs and symptoms of hypersensitivity reactions and seek immediate medical care should a reaction occur.

DEPRESSION

In the controlled clinical trials of BENLYSTA IV, psychiatric events were reported more frequently with BENLYSTA than with placebo, related primarily to depression-related events, insomnia and anxiety. Serious psychiatric events were reported in trials with BENLYSTA. Serious depression and suicidality (including two completed suicides) were reported in trials with BENLYSTA IV. There were no serious depression-related events or suicides reported in the BENLYSTA SC trial. Instruct patients to contact their healthcare provider if they experience new or worsening depression, suicidal thoughts, or other mood changes.

MALIGNANCY

The impact of treatment with BENLYSTA on the development of malignancies is not known. The mechanism of action of BENLYSTA could increase the risk for the development of malignancies.

IMMUNIZATION

Live vaccines should not be given for 30 days before or concurrently with BENLYSTA. BENLYSTA may interfere with the response to immunizations.

USE WITH BIOLOGIC THERAPIES OR IV CYCLOPHOSPHAMIDE

BENLYSTA has not been studied in combination with other biologic therapies, including B-cell targeted therapies, or IV cyclophosphamide. Therefore, use of BENLYSTA is not recommended in combination with these therapies.

ADVERSE REACTIONS

The most common serious adverse reactions were serious infections (6.0% and 5.2% in patients receiving BENLYSTA IV and placebo, respectively), some of which were fatal. Adverse reactions, regardless of causality, occurring in at least 3% of patients with SLE who received BENLYSTA 10 mg/kg and placebo respectively and, at an incidence at least 1% greater than that observed with placebo in the 3 controlled studies, were: nausea 15% and 12%; diarrhea 12% and 9%; pyrexia 10% and 8%; nasopharyngitis 9% and 7%; bronchitis 9% and 5%; insomnia 7% and 5%; pain in extremity 6% and 4%; depression 5% and 4%; migraine 5% and 4%; pharyngitis 5% and 3%; cystitis 4% and 3%; leukopenia 4% and 2%; viral gastroenteritis 3% and 1%.

The safety profile observed for BENLYSTA SC plus standard therapy was consistent with the known safety profile of BENLYSTA IV plus standard therapy, with the exception of local injection site reactions.

OTHER IMPORTANT INFORMATION FOR BENLYSTA

USE IN SPECIFIC POPULATIONS

Pregnancy: There are insufficient data on use of BENLYSTA in pregnant women to establish whether there is drug-associated risk for major birth defects or miscarriage. Following an assessment of benefit versus risk, if prevention is warranted, women of childbearing potential should use effective contraception during treatment and for at least 4 months after the final treatment.

Pregnancy Registry: Healthcare professionals are encouraged to register patients and pregnant women are encouraged to enroll themselves by calling 1-877-681-6296.

Lactation: There is no information available on the presence of belimumab in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BENLYSTA and any potential adverse effects on the breastfed child from BENLYSTA or from the underlying maternal condition.

Black/African American Patients: In clinical studies, there have been mixed results regarding how well BENLYSTA works in black/African American patients. Consider the risks and benefits when prescribing BENLYSTA in black/African American patients.

Please see full Prescribing Information and Medication Guide for BENLYSTA.

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