GSK announces positive results in fourth consecutive pivotal trial of Benlysta® (belimumab) in SLE

Data in Japan, China and South Korea will form basis of new regulatory submissions for Benlysta

GSK today announced positive efficacy and safety data from a pivotal study of patients with systemic lupus erythematosus (SLE) in Northeast Asia (Japan, China and South Korea). In the study, being presented at the 2016 American College of Rheumatology/Association for Rheumatology Health Professionals Annual Meeting (ACR/AHRP), Benlysta^® achieved the primary and all four pre-specified secondary endpoints with statistical significance. The information obtained will be used to submit files for the regulatory approval of belimumab in Japan and China in the next few months.

For the primary efficacy endpoint (SLE Responder Index at Week 52), significantly more of the patients on belimumab 10mg/kg administered intravenously (54%) achieved reduced disease activity compared to those on placebo (40%) (Odds Ratio: 2.03; 95% CI: 1.43-2.88; p<0.0001). SRI is a comprehensive composite endpoint measure, the components of which measure reduction in disease activity defined as clinical improvement (³4‑point improvement in SELENA-SLEDAI, [SS]) with no significant worsening in any organ system (BILAG) and no worsening in overall patient condition (PGA).

The benefits of belimumab were also seen for all the secondary endpoints in the study. The key secondary endpoint relating to average steroid reduction in patients with baseline dose of >7.5mg/day prednisone was significant (p=0.0228), favouring belimumab. In addition 56% of patients on belimumab achieved a ≥4 point reduction in SS at Week 52 (versus 42% on placebo, p=0.0001); 33% of belimumab patients achieved an SRI7 response rate (versus 23% on placebo, p=0.0099); and the belimumab group had a 50% lower risk of experiencing a severe flare versus placebo, as measured by the Severe Flare Index (p=0.0004).

The safety profile of belimumab observed in the study was consistent with that observed in previous IV and subcutaneous belimumab studies, with the overall incidence of adverse events being similar in both the belimumab (75%) versus placebo (76%) groups. Fewer serious adverse events occurred in the belimumab group compared to the placebo group (12% versus 18%). There were no deaths in the belimumab group and 1 in the placebo group. No new safety issues were identified.

David Roth, Project Lead for Benlysta at GSK, said, “Outside of South Korea, where Benlysta has already been granted approval, there is currently no approved biologic treatment option for lupus patients in Northeast Asia, so in the context of the unmet medical need in the region, this study result is extremely important. The data also reinforces our belief that the belimumab mechanism of action is central to disease activity in SLE and we are pleased that the benefit/risk profile remains favourable for patients. Based on this data and subsequent regulatory submissions, we hope to be able to make Benlysta available to more patients living with lupus in this region.”

About the Study

A total of 707 patients in Japan, China and South Korea with SLE who were at least 18 years of age , with a SELENA SLEDAI score of ≥ 8 were recruited into the Phase 3, randomized, placebo-controlled, 52-week study to evaluate the efficacy and safety of 10mg/kg belimumab administered intravenously (IV) in addition to standard of care (SoC) relative to placebo.  Patients received 14 doses of study medication over 48 weeks and were then evaluated at Week 52 for the primary efficacy endpoint.   Ninety-three percent of the patients in both the belimumab and placebo arms of the study were female with Median disease duration of 5 years.  The primary endpoint was the SLE responder index (SRI) response rate at Wk 52 (reduction ≥4 points in SS score; no worsening (<0.3 increase) in Physician’s Global Assessment (PGA); no new British Isles Lupus Assessment Group (BILAG A domain score or 2 new BILAG B domain scores vs baseline. Secondary endpoints included percent of patients with ≥4 point reduction in SS score over baseline at Wk 52, SRI7 responders (SRI where the reduction in SS is ≥7 points reduction rather than 4) at Wk 52, number of days of daily prednisone dose ≤7.5mg and/or reduced by 50% over 52 wks, and time to first severe SLE flare (using the modified SLE Flare Index).

About Benlysta^® (belimumab), for injection, for intravenous use only

Benlysta is the first medicine specifically developed and approved for SLE in over 50 years. 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.

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.

Full 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

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

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 only.

Important Safety Information for belimumab

Please consult the full Prescribing Information for all the labelled safety information for Benlysta (belimumab) for injection, for intravenous use only.

CONTRAINDICATION

Benlysta is contraindicated in patients who have had anaphylaxis with belimumab.

WARNINGS AND PRECAUTIONS

MORTALITY

There were more deaths reported with Benlysta than with placebo during the controlled period of the clinical trials. Out of 2133 patients in 3 clinical trials, a total of 14 deaths occurred in the following groups: 3/675 in placebo, 5/673 in Benlysta 1 mg/kg, 0/111 in Benlysta 4 mg/kg, and 6/674 in Benlysta 10 mg/kg. No single cause of death predominated. Etiologies included infection, cardiovascular disease, and suicide.

SERIOUS INFECTIONS

Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents, including Benlysta. Caution should be exercised when considering use in patients with a history of chronic infections. Patients receiving therapy for a chronic infection should not receive Benlysta. Consider interrupting therapy with Benlysta in patients who develop a new infection while receiving Benlysta. The most frequent serious infections included pneumonia, urinary tract infection, cellulitis, and bronchitis.

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. Patients presenting with new-onset or deteriorating neurological signs and symptoms should be evaluated for PML by an appropriate specialist. If PML is confirmed, consider stopping immunosuppressant therapy, including Benlysta.

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 of malignancies.

HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS) AND INFUSION REACTIONS

Acute hypersensitivity reactions, including anaphylaxis and death, have been reported with 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. Hypersensitivity, including serious reactions, has occurred in patients who have previously tolerated infusions of Benlysta. Patients with a history of multiple drug allergies or significant hypersensitivity may be at increased risk. Some patients received premedication; however, there is insufficient evidence to determine whether premedication diminishes the frequency or severity of these reactions.

Healthcare providers should be aware of the risk of hypersensitivity reactions, which may present as infusion reactions, and monitor patients closely. Manifestations of hypersensitivity included hypotension, angioedema, urticaria or other rash, pruritus, and dyspnea.  In the event of a serious hypersensitivity reaction, discontinue Benlysta immediately and administer appropriate medical therapy. Infusion-associated adverse events were also reported. Serious infusion reactions included bradycardia, myalgia, headache, rash, urticaria, and hypotension. In the event of an infusion reaction, the infusion rate may be slowed or interrupted.

Patients should be informed of the signs and symptoms of an acute hypersensitivity reaction and be instructed to seek immediate medical care should a reaction occur.

DEPRESSION

In clinical trials, psychiatric events (primarily depression, insomnia, and anxiety) were reported more frequently with Benlysta than with placebo. Serious psychiatric events, serious depression, and two suicides were also reported. It is unknown if treatment with Benlysta is associated with increased risk for these events. Patients should be instructed to contact their healthcare provider if they experience new or worsening depression, suicidal thoughts, or other mood changes.

IMMUNISATION

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

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 and placebo, respectively). 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 least1% 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%.

Other Important Information for Benlysta

USE IN SPECIFIC POPULATIONS

Pregnancy: Category C. Benlysta should be used during pregnancy only if the potential benefit outweighs the risk. Women of childbearing potential should use adequate contraception during treatment with Benlysta and for at least 4 months after the last dose.

Populations not studied: Benlysta has not been studied in the following patient groups, and is not recommended in patients with:

∙ severe active central nervous system lupus

∙ severe active lupus nephritis

∙ HIV

∙ a history of, or current, hepatitis B or C

∙ hypogammaglobulinaemia (IgG <400 mg/dl) or IgA deficiency (IgA <10 mg/dl)

∙ a history of major organ transplant or hematopoietic stem /cell /marrow transplant or renal transplant.

Effect in black/African American patients: In exploratory analyses of 2 Phase III trials, response rates were lower for black patients (N=148) in the groups receiving Benlysta relative to black patients in the placebo group. In the Phase II trial, black patients (N=106) in the groups receiving Benlysta did not appear to have a different response than the rest of the study population. Although no definitive conclusions can be drawn from these analyses, caution should be used when considering Benlysta  for black/African American patients.

About SLE

Systemic lupus erythematosus (SLE) is the most common form of lupus, affecting approximately 70 percent of an estimated five million people with lupus worldwide. It is a chronic, incurable autoimmune disease producing autoantibodies that can attack almost any system in the body.

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Cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D 'Risk factors' in the company's Annual Report on Form 20-F for 2014.