Well-established safety profile based on the largest lupus clinical trial program

BENLYSTA is the only biologic for lupus and lupus nephritis studied in more than 7000 patients over 11+ years.

The safety profile of BENLYSTA has been established across a diverse patient population1-7

Adults with lupus

Children 5 years and older with lupus

Adults of African descent with lupus

Adults with lupus nephritis

Post-marketing safety trial in adults with lupus

7000

+

patients with lupus have been included in trials of BENLYSTA, including a clinical trial in patients with lupus nephritis (N=448)1-7

Lupus safety profile

The safety profile of BENLYSTA is well-established across clinical trials, including trials in intravenous and subcutaneous administration, and a long-term extension study.

IV formulation

Incidence of adverse reactions in IV trials (adult Phase II, BLISS-52, and BLISS-76)

In ≥3% of patients treated with BENLYSTA IV 10 mg/kg + ST and ≥1% more frequently than in patients receiving placebo + ST in the 52-week Phase II trial, BLISS-52, and BLISS-76

Adverse reactions BENLYSTA 10 mg/kg (n=674) Placebo (n=675)
Nausea 15% 12%
Diarrhea 12% 9%
Pyrexia 10% 8%
Nasopharyngitis 9% 7%
Bronchitis 9% 5%
Insomnia 7% 5%
Pain in extremity 6% 4%
Depression 5% 4%
Migraine 5% 4%
Pharyngitis 5% 3%
Cystitis 4% 3%
Leukopenia 4% 2%
Gastroenteritis 3% 1%

Adverse reactions in the BLISS-LN and PLUTO trials were consistent with those in adult IV trials.

Adverse reactions in the EMBRACE trial were consistent with the known safety profile of BENLYSTA administered IV + ST in the overall population.7

BASE (post-marketing trial of 4003 adult patients) demonstrated rates of AEs consistent with the pivotal trials and higher rates of serious infusion/hypersensitivity reactions, fatal reactions, and serious psychiatric events.7

AE = adverse event; BASE = Belimumab Assessment of Safety in SLE; BLISS-LN = Belimumab International Study in Lupus Nephritis; EMBRACE = Efficacy and Safety of Belimumab in Adult Subjects of Black Race; IV = intravenous; PLUTO = Pediatric Lupus Trial of BENLYSTA; ST = standard therapy.

SC formulation

The safety profile was consistent with the known safety profile of BENLYSTA IV + ST, with the exception of local injection site reactions

  • Injection site reactions in BENLYSTA + ST group: 6.1%

  • Injection site reactions in placebo + ST group: 2.5%

  • Most common injection site reactions: pain, erythema, hematoma, pruritus, and induration

SC = subcutaneous.

Long-term safety results

Safety data observed over 7 years8

Long-term safety was assessed in the open-label BLISS-76 LTE (US participants only)

Primary endpoint (safety) results (N=268) (at any time post-baseline)
Most frequent AEs (≥25%)
Arthralgia 40.3%
Nausea 32.8%
Headache 32.1%
Infections
Bacterial upper respiratory tract infection 28.7%
Viral upper respiratory tract infection 28.4%
Bacterial urinary tract infection 26.1%
≥1 SAE 41.8%
≥1 severe SAE (grade 3 or 4 events listed as life- threatening) 37.3%
Discontinuation due to an AE 9.7%

Over the 7-year follow-up, the rate of treatment-emergent AEs remained stable.8

Results are descriptive. Exploratory results should be interpreted with additional care.

See study design.

See study limitations.

LTE = long-term extension; SAE = serious adverse event.

Lupus nephritis safety profile

Adverse events observed in BLISS-LN were consistent with the known safety profile of BENLYSTA IV in patients with lupus.

Incidence of adverse events in the 104-week BLISS-LN trial9

CYC/AZA arm
At least one, % BENLYSTA IV + ST (n=60) Placebo + ST (n=59)
AE 93.3% 91.5%
Related AE 58.3% 52.5%
Serious AE 30.0% 23.7%
Severe AE 26.7% 22.0%
AE resulting in IP discontinuation 13.3% 8.5%
On-treatment fatal serious AEs which resulted in death on or off treatment 1.7% 0%
Additional deaths occurring after the treatment period 0% 0%
MMF arm
At least one, % BENLYSTA IV + ST (n=164) Placebo + ST (n=165)
AE 96.3% 95.2%
Related AE 53.7% 53.3%
Serious AE 24.4% 32.1%
Severe AE 23.2% 21.2%
AE resulting in IP discontinuation 12.8% 14.5%
On-treatment fatal serious AEs which resulted in death on or off treatment 1.8% 1.8%
Additional deaths occurring after the treatment period 1.2% 1.2%
Average across both arms
At least one, % BENLYSTA IV + ST (n=224) Placebo + ST (n=224)
AE 95.5% 94.2%
Related AE 54.9% 53.1%
Serious AE 25.9% 29.9%
Severe AE 24.1% 21.2%
AE resulting in IP discontinuation 12.9% 12.9%
On-treatment fatal serious AEs which resulted in death on or off treatment 1.8% 1.3%
Additional deaths occurring after the treatment period 0.9% 0.9%
  • AZA = azathioprine; CYC = cyclophosphamide; IP = investigational product; MMF = mycophenolate mofetil.

Adverse events in the BLISS-LN trial were consistent with those observed in adult IV trials conducted in patients with lupus

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BENLYSTA for lupus

BENLYSTA improved key clinical outcomes for appropriate patients.

SEE EFFICACY DATA

BENLYSTA for lupus nephritis

BENLYSTA improved key clinical outcomes for appropriate patients.

SEE LN EFFICACY DATA

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Indication & Safety Info

Indication

Important Safety Information

Indication

BENLYSTA is indicated for patients aged ≥5 with active systemic lupus erythematosus (SLE) or active lupus nephritis who are receiving standard therapy. BENLYSTA is not recommended in patients with severe active central nervous system lupus.

Important Safety Information

CONTRAINDICATION

Previous anaphylaxis with BENLYSTA.

WARNINGS AND PRECAUTIONS

Serious Infections: Serious and sometimes fatal infections have been reported and occurred more frequently with BENLYSTA. Use caution in patients with severe or chronic infections, and consider interrupting therapy in patients with a new infection.

 

Progressive Multifocal Leukoencephalopathy (PML): Cases of JC virus-associated PML resulting in neurological deficits, including fatal cases, have been reported. If PML is suspected, immunosuppressant therapy, including BENLYSTA, must be suspended until PML is excluded. If confirmed, stop immunosuppressant therapy, including BENLYSTA.

 

Hypersensitivity Reactions (Including Anaphylaxis): Acute hypersensitivity reactions, including anaphylaxis and death, and infusion-related reactions have been reported. Generally, reactions occurred within hours of the infusion but may occur later, including in patients who have previously tolerated BENLYSTA. Non-acute hypersensitivity reactions (eg, rash, nausea, fatigue, myalgia, headache, and facial edema) typically occurred up to a week after infusion. Monitor patients during and after treatment and be prepared to manage anaphylaxis and infusion-related reactions. Be aware of the risk of hypersensitivity reactions, which may present as infusion-related reactions. Discontinue immediately in the event of a serious reaction. With intravenous administration, if an infusion reaction develops, slow or interrupt the infusion.

 

Depression and Suicidality: Depression and suicidality were reported in patients receiving BENLYSTA. Before adding BENLYSTA, assess patients’ risk of depression and suicide and monitor them during treatment. Instruct patients/caregivers to contact their HCP if they experience new/worsening depression, suicidal thoughts/behavior, or other mood changes.

 

Malignancy: There is an increased risk of malignancies with the use of immunosuppressants. The impact of BENLYSTA on the development of malignancies is unknown.

 

Immunization: Live vaccines should not be given for 30 days before or concurrently with BENLYSTA as clinical safety has not been established.

 

Use With Biologic Therapies: Available data do not support the safety and efficacy of concomitant use of BENLYSTA with rituximab in patients with SLE. An increased incidence of serious infections and post-injection systemic reactions in patients receiving BENLYSTA concomitantly with rituximab compared to patients receiving BENLYSTA alone has been observed. The safety and efficacy of BENLYSTA concomitantly with other biologic therapies, including B-cell-targeted therapies, have not been established. Caution should be exercised if BENLYSTA is administered in combination with other biologic therapies.

 

ADVERSE REACTIONS

The most common serious adverse reactions in adult SLE clinical trials were serious infections; some were fatal. The most common adverse reactions (≥5%) were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, pharyngitis, and injection site reactions (subcutaneous injection).

 

Adverse reactions reported in clinical trials with SLE pediatric patients (≥5 years) and adult patients with lupus nephritis were consistent with those observed in adult SLE trials.

 

USE IN SPECIFIC POPULATIONS

Pregnancy: There are insufficient data in pregnant women to establish whether there is drug-associated risk for major birth defects or miscarriage. After a risk/benefit assessment, if prevention is warranted, women of childbearing potential should use contraception during treatment and for ≥4 months after the final treatment.

 

Pregnancy Registry: HCPs are encouraged to refer patients and pregnant women are encouraged to enroll themselves by calling 1-877-311-8972 or visiting https://mothertobaby.org/ongoing-study/benlysta-belimumab/.

 

Please see full Prescribing Information and Medication Guide for BENLYSTA.

To report SUSPECTED ADVERSE REACTIONS, contact GSK at gsk.public.reportum.com or 1-888-825-5249, or
FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

References

  1. 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.

  2. 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 Rheumatol. 2011;63(12):3918-3930.

  3. 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.

  4. Brunner HI, Abud-Mendoza C, Viola DO, et al. Safety and efficacy of intravenous belimumab in children with systemic lupus erythematosus: results from a randomised, placebo-controlled trial. Ann Rheum Dis. 2020;79(10):1340-1348.

  5. Furie R, Rovin BH, Houssiau F, et al. Two-year, randomized, controlled trial of belimumab in lupus nephritis. N Engl J Med. 2020;383:1117-1128.

  6. Ginzler E, Guedes Barbosa LS, D'Cruz D, et al. Phase III/IV, randomized, fifty-two-week study of the efficacy and safety of belimumab in patients of Black African ancestry with systemic lupus erythematosus. Arthritis Rheumatol. 2022;74(1):112-123.

  7. Sheikh SZ, Scheinberg MA, Wei JC, et al. Mortality and adverse events of special interest with intravenous belimumab for adults with active, autoantibody-positive systemic lupus erythematosus (BASE): a multicentre, double-blind, randomised, placebo-controlled, phase 4 trial. Lancet Rheumatol. 2021;3(2):E122-E130.

  8. Furie RA, Wallace DJ, Aranow C, et al. Long-term safety and efficacy of belimumab in patients with systemic lupus erythematosus: a continuation of a seventy-six-week Phase III parent study in the United States. Arthritis Rheumatol. 2018;70(6):868-877.

  9. Data on file, GSK.