Last updated Feb. 1, 2023, by Marisa Wexler, MS
Fact-checked by Joana Carvalho, PhD
What is Benlysta for Lupus?
Benlysta (belimumab) is a monoclonal antibody approved to treat people with active systemic lupus erythematosus (SLE) or active lupus nephritis. It can be administered via into-the-vein infusion or injection under the skin. It is marketed by GSK, formerly known as GlaxoSmithKline.
How does Benlysta work?
B-cells are a type of immune cell responsible for producing antibodies, which help the body fight off infections by sticking to viruses and bacteria and directing an immune attack against the infectious invader. In lupus, B-cells produce antibodies that direct an attack against the body’s own healthy cells, referred to as autoantibodies.
Benlysta is designed to reduce the production of disease-driving autoantibodies by lowering B-cell activity. The therapy doesn’t bind to B-cells directly. Instead, it blocks the activity of a protein in the blood called B-lymphocyte stimulator (BLyS). Normally, BLyS in the blood (referred to as “soluble” BLyS) interacts with B-cells to promote their survival and activation. By blocking BLyS, Benlysta reduces the activity of these immune cells.
Who can take Benlysta?
Benlysta is approved in the U.S. to treat patients 5 and older who have SLE, the most common form of lupus, or lupus nephritis, a dangerous complication of lupus marked by kidney inflammation.
It was originally approved by the U.S. Food and Drug Administration (FDA) in 2011 for active lupus in adults. In 2020, its approval was extended to adults with lupus nephritis. Benlysta was approved to treat lupus in children in 2019 and to treat lupus nephritis in this younger patient population in 2022.
Who should not take Benlysta?
Benlysta should not be taken by anyone who has had an allergic reaction to the medication. The medication has not been evaluated in people with severe active central nervous system lupus and it’s not recommended for people with this complication.
Data from clinical trials suggest Black patients may be less likely to respond to Benlysta than people of other racial backgrounds. Patients are advised to talk about the potential risks and benefits of the therapy with their healthcare teams.
How is Benlysta administered?
Benlysta can be administered via into-the-vein infusion directly into the bloodstream or through an under-the-skin (subcutaneous) injection. Administering it intravenously is approved for patients ages 5 and older, while subcutaneous dosing is only approved for adults.
The approved intravenous dosage is 10 mg/kg, given at two-week intervals for the first three doses, and at four-week intervals thereafter. Each infusion takes about an hour and it’s recommended that patients receive preventive medication before each infusion to decrease the risk of infusion reactions or allergic reactions.
The approved subcutaneous dose in SLE is 200 mg once weekly, while the approved dose for lupus nephritis is 400 mg (two 200 mg injections) once weekly for the first four doses, followed by 200 mg once weekly thereafter.
Benlysta in clinical trials
Intravenous Benlysta in adults with SLE
The initial approval of Benlysta was supported by data from a pair of Phase 3 trials — BLISS-76 (NCT00410384) and BLISS-52 (NCT00424476) — that collectively enrolled more than 1,600 adults with SLE at sites in North and South America, Asia, Europe, and Australia. Participants were randomly assigned to receive Benlysta at one of two doses (1 or 10 mg/kg) or a placebo for at least 52 weeks (one year), in addition to standard therapy.
All the participants were positive for autoantibodies and more than 70% in both trials were taking at least two other lupus medicines, including corticosteroids, antimalarial agents, and/or immunosuppressive therapies.
In both studies, the main goal was to determine the number of patients who met the SLE Responder Index-4 (SRI-4) criteria after a year. SRI-4 is a composite measure of disease severity that basically means patients have improved in some measures of disease activity, without worsening in others.
In both trials, the proportion of patients achieving SRI-4 was significantly higher among those treated with 10 mg/kg of Benlysta than in those given a placebo (43% vs. 34% in BLISS-76, 58% vs. 44% in BLISS-52). The lower dose also showed positive trends in SRI-4 rates, but the results were only statistically significant in BLISS-52.
In both trials fewer patients on 10 mg/kg Benlysta than on a placebo had a severe disease flare (a sudden worsening of symptoms).
An exploratory analysis of 148 Black participants across both studies showed that, in this racial group, the SRI-4 response rate was higher among those given a placebo than in those on Benlysta.
This prompted the launch of the Phase 4 EMBRACE study (NCT01632241) that compared 10 mg/kg Benlysta against a placebo on top of standard therapy in 448 Black SLE patients. The trial had a similar design to the earlier studies and again the goal was to determine the patient response rate through another composite measure of disease activity. Results showed the response rate was higher among patients given Benlysta (49% vs. 42%), though the difference was not considered statistically significant compared with the placebo.
Intravenous Benlysta in pediatric SLE
Benlysta’s approval for children with SLE was supported by data from a Phase 2 trial called PLUTO (NCT01649765) that enrolled 93 children with SLE. Participants were randomly assigned to receive 10 mg/kg Benlysta or a placebo, on top of standard therapy, for a year. Like the initial studies of SLE in adults, the main goal of PLUTO was to determine the patient responder rate based on SRI-4.
Results showed that the responder rate was higher among patients on Benlysta than a placebo (53% vs. 44%), though the difference between the groups did not reach statistical significance. The proportion of children who had a severe disease flare was lower among those on Benlysta compared with a placebo (17% vs. 35%), reflecting a 64% lower risk of having a severe flare over a year.
Subcutaneous Benlysta in SLE
The safety and effectiveness of Benlysta by a subcutaneous injection were assessed in a Phase 3 trial called BLISS-SC (NCT01484496) that enrolled 836 adults with SLE. Participants were randomized to be treated with subcutaneous Benlysta (200 mg once weekly) or a placebo, on top of standard therapy, for a year. As in studies assessing the safety and effectiveness of intravenous Benlysta, the main goal of BLISS-SC was to determine patient responder rate based on SRI-4.
Results showed the SRI-4 responder rate was significantly higher for patients on Benlysta than those given a placebo (61% vs. 48%) after a year. In an exploratory analysis of 91 Black patients, the response rate was slightly higher among those on Benlysta compared with a placebo (45% vs. 39%). Severe disease flares were seen in 11% on Benlysta compared with 18% on a placebo, indicating patients with Benlysta had a 49% lower risk of having at least one severe lupus flare over a year.
Intravenous Benlysta in lupus nephritis
Benlysta’s approval for adults with lupus nephritis was supported by data from a Phase 3 trial called BLISS-LN (NCT01639339) that enrolled 448 adults with this lupus complication at sites in Asia, North America, South America, and Europe. Participants were randomly assigned to receive Benlysta at 10 mg/kg or a placebo for two years.
The study’s main goal was to determine the patient response rate based on the Primary Efficacy Renal Response (PERR), a composite measure of kidney function. After two years, the proportion of PERR responders was significantly higher among those on Benlysta compared with a placebo (43% vs. 32%).
A similar difference was seen at one year (47% vs. 35%) and other measures of kidney function also generally favored Benlysta. Patients on Benlysta were significantly less likely than those on a placebo to die or experience a serious kidney-related health event.
Common side effects of Benlysta
The most common side effects of Benlysta include:
- nausea
- diarrhea
- fever
- the common cold
- bronchitis (lung inflammation)
- insomnia
- pain in the extremities
- depression
- migraine
- sore throat
- injection site reactions (with the subcutaneous administration only)
Serious infection risks
Benlysta works by reducing the activation of the immune system, which normally helps protect the body against infection. Serious and sometimes fatal infections have occurred in people taking Benlysta. Caution should be used if it’s being used in someone with a history of severe or chronic infections, and treatment should be interrupted if a new infection develops.
If patients show symptoms of neurological damage, they should be evaluated for a rare form of brain infection called progressive multifocal leukoencephalopathy (PML). If PML is diagnosed, it’s recommended to consider discontinuing Benlysta and other immune-suppressing medicines.
Due to the risk of infection and related complications, vaccines that contain a live virus should not be given to those on Benlysta.
Allergic reactions
Allergic reactions to Benlysta, including serious and fatal allergic reactions, have been reported. If patients show signs of a serious allergic reaction, Benlysta should be discontinued immediately and an appropriate treatment should be started.
Depression and suicidality
Depression and suicidality have been reported in trials of Benlysta. Patients should undergo a mental health evaluation before starting treatment and should be monitored during treatment. Those on Benlysta should contact their healthcare team if they experience new or worsening mood changes.
Use in pregnancy and breastfeeding
There is not enough data on using Benlysta in pregnancy to determine whether treatment affects the risk of miscarriage or complications for the fetus. Data from animals have generally shown no toxicity for the fetus when Benlysta is used during pregnancy, though some data suggest treatment may affect the immune system’s development.
A registry monitors patient outcomes when Benlysta is used during pregnancy. Clinicians can register their pregnant patients by calling 1-877-681-6296.
There is no data on using Benlysta while breastfeeding. The benefits and potential risks of using or stopping Benlysta during pregnancy should be discussed by the patient and healthcare team.
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