GSK: We are delighted to start the phase III study and evolve our research programme for belimumab in systemic lupus erythematosus (SLE)

LONDON, 22-Mar-2018 — /EuropaWire/ — GSK today announced the start of a phase III study investigating Benlysta (belimumab) in combination with rituximab in adult patients with systemic lupus erythematosus (SLE). Belimumab and rituximab have different but potentially complementary mechanisms of action. This study will assess whether co-administration enhances the treatment effect of belimumab and provides sustained disease control, which could lead to clinical remission. SLE is a chronic, incurable, autoimmune disease associated with a range of symptoms that can fluctuate over time, affecting almost any system in the body.

Gijs van den Brink, Global Head, Immuno-Inflammation Research and Clinical Development, GSK said, “We are delighted to start this study and evolve our research programme for belimumab in SLE. Belimumab has already demonstrated its consistent efficacy in reducing disease activity for patients with SLE, with four successful phase III trials. The underlying biology of the disease, combined with the results from a small investigator-sponsored study in severe refractory SLE, provide a strong scientific rationale for initiating this study. Our aim with this study is to assess whether the combination treatment will not only achieve a state of low disease activity, but potentially also achieve clinical remission in patients living with this chronic and unpredictable disease.”

At least 200 patients with active SLE indicated by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K score of 6 or more will be randomised to receive either belimumab plus rituximab-placebo, plus standard therapy (control arm); belimumab plus rituximab, plus standard therapy (combination arm); or belimumab plus standard therapy (reference arm); the control and combination arms will have background immunosuppressants discontinued by Week 4 and all three arms will have a corticosteroid taper. The primary endpoint of the study is disease control defined as a SLEDAI-2K score <2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <5 mg/day at Week 52. Clinical remission (defined as a Clinical SLEDAI-2K score=0 at Week 64) and durable response (defined as maintenance of disease control achieved at Week 104) with no treatment other than antimalarials, are major secondary endpoints. Safety and tolerability will also be assessed. The study is anticipated to complete in 2021.

Belimumab, a monoclonal antibody, is currently the only biologic medicine specifically approved to treat SLE anywhere in the world.

About the phase III study

The pivotal phase III study named BLISS-BELIEVE is a multi-centre, three-arm, randomised, double-blind, placebo-controlled, 104-week superiority study in at least 200 adult patients with SLE to evaluate the efficacy and safety of belimumab administered in combination with a single cycle of rituximab. Patients will be randomly assigned in a 1:2:1 ratio to one of three treatment arms all on a background of standard therapy including corticosteroids, immunosuppressants and antimalarials; belimumab plus rituximab-placebo (control), belimumab plus rituximab (combination), or open-label belimumab plus standard therapy (reference). Blinded independent assessors will conduct the SLEDAI-2K at key time points.

The control and combination arms are double-blind; patients will receive belimumab subcutaneous 200 mg/week for 51 weeks. The reference arm is open-label and patients will receive belimumab subcutaneous 200 mg/week and standard therapy for 104 weeks. Rituximab (1000 mg) or placebo will be administered as an intravenous infusion at Weeks 4 and 6 for the combination and control arms respectively.  Patients in the control or combination arms who enter the study on immunosuppressants will discontinue immunosuppressants by Week 4. After the initial 12 weeks of study treatment, a corticosteroid taper to <5 mg/day by Week 26 will be initiated and conducted under the direction of the investigator for participants in all three arms.

About Benlysta (belimumab)

Benlysta is currently the only medicine specifically developed and approved for SLE. Benlysta, a BLyS-specific inhibitor, is a human monoclonal antibody that binds to soluble BLyS. Benlysta does not bind B cells directly. By binding BLyS, Benlysta inhibits the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells.

Benlysta is available as 120 mg in a 5-mL single-use vial and 400 mg in a 20-mL single-use vial for injection, for intravenous use. Benlysta is available as a 200mg single-dose autoinjector or prefilled syringe for subcutaneous injection.

Benlysta is licensed in the European Union as an add-on therapy in adult patients with active autoantibody-positive SLE, with a high degree of disease activity (e.g. positive anti-dsDNA and low complement), despite standard therapy.

For the EU Summary of Product Characteristics for Benlysta, please visit www.ema.europa.eu

Benlysta is licensed in the US 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.

Benlysta is indicated for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy. Full US prescribing information including Medication Guide is available at: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Benlysta/pdf/BENLYSTA-PI-MG.PDF

About rituximab

Rituximab is an anti-CD20 monoclonal antibody, marketed by Roche under the brand names MabThera and Rituxan. It was originally approved to treat certain types of cancer and has since been approved in the treatment of certain autoimmune conditions. It is administered intravenously and works by targeting and depleting B-cells.

Rituximab is not approved for the treatment of SLE.

About systemic lupus erythematosus (SLE)

Systemic lupus erythematosus (SLE) is the most common form of lupus, affecting approximately 70 percent of an estimated 5 million people with lupus worldwide. SLE is a chronic, incurable, autoimmune disease associated with a range of symptoms that can fluctuate over time including painful or swollen joints, extreme fatigue, unexplained fever, skin rashes and organ damage.

Important Safety Information (ISI) for belimumab

The following ISI is based on the Highlights section of the US Prescribing Information for Benlysta. Please consult the full Prescribing Information for all the labelled safety information for Benlysta.

CONTRAINDICATION

Previous anaphylaxis with BENLYSTA.

WARNINGS AND PRECAUTIONS

Mortality: There were more deaths reported with BENLYSTA than with placebo during the controlled period of clinical trials.

Serious Infections: Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents, including BENLYSTA. Use with caution in patients with severe or chronic infections. Consider interrupting therapy with BENLYSTA if patients develop a new infection during treatment with BENLYSTA.

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: Serious and fatal reactions have been reported. BENLYSTA for intravenous use should be administered by healthcare providers prepared to manage anaphylaxis. Monitor patients during and for an appropriate period of time after intravenous administration of BENLYSTA. Patients should be informed of the signs and symptoms of hypersensitivity reactions and be instructed to seek immediate medical care should a reaction occur.

Depression: Depression and suicidality have been reported in trials with BENLYSTA. Patients should be instructed 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 or concurrently with BENLYSTA as clinical safety has not been established.

Common adverse reactions (>5%): nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, pharyngitis, and injection site reactions (subcutaneous administration).

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.

GSK – a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit www.gsk.com/en-gb/about-us/.

SOURCE: GlaxoSmithKline plc.

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