GlaxoSmithKline and Human Genome Sciences initiate phase III trial of belimumab (Benlysta®) administered subcutaneously in subjects with systemic lupus erythematosus

GlaxoSmithKline (GSK) and Human Genome Sciences, Inc. (Nasdaq: HGSI) today announced that dosing has been initiated in BLISS-SC, a new Phase III trialto evaluate the efficacy, safety and tolerability of BENLYSTA® (belimumab) administered subcutaneously (SC) once-weekly to autoantibody-positive adults with active systemic lupus erythematosus (SLE).

“Initiation of this new trial investigating a subcutaneous formulation of BENLYSTA represents an important step in our ongoing clinical development programme,” said H. Thomas Watkins, President and Chief Executive Officer, Human Genome Sciences (HGS).

About the Design of BLISS-SC

BLISS-SC is a Phase III, multi-centre, international, randomised, double-blind, placebo-controlled, 52-week study to investigate use of belimumab administered subcutaneously once-weekly in autoantibody-positive adult subjects with active SLE.

Approximately 816 SLE subjects will be randomised to one of two arms, with a target of 544 subjects receiving belimumab 200 mg weekly plus standard of care (SOC) and 272 subjects receiving placebo plus SOC. Subjects completing the 52-week double-blind period can enter a 6-month open-label extension in which all subjects will receive belimumab 200 mg SC weekly.

The primary efficacy endpoint of BLISS-SC is response rate at week 52, as measured by the SLE Responder Index (SRI) defined as:

• A reduction from baseline of at least 4 points on the SELENA-SLEDAI; and
• No worsening (increase of <0.30 points from baseline) in Physician’s Global Assessment (PGA); and
• No new BILAG A organ domain score (which would indicate a severe flare of lupus disease activity) or 2 new BILAG B organ domain scores (which would indicate a moderate flare of disease activity) compared with baseline at the time of assessment.

BLISS-SC is being conducted at over 200 sites globally. Initial results from the trial are anticipated in the second half of 2014. Data from this study will be subject to evaluation and approval by regulatory authorities before belimumab could be made available in a subcutaneous formulation.

About BENLYSTA (belimumab)

Belimumab is the first in a drug class known as BLyS-specific inhibitors. Belimumab was approved by the U.S. Food and Drug Administration (FDA) on March 9, 2011 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 belimumab has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Belimumab has not been studied in combination with other biologics or intravenous cyclophosphamide. Use of belimumab is not recommended in these situations. Belimumab is currently administered as a one-hour intravenous infusion given at 2-week intervals for the first 3 doses and at 4-week intervals thereafter.

In Europe, belimumab was approved by the European Commission on 13th July 2011. It is indicated as an add-on therapy in adult patients with active autoantibody-positive systemic lupus erythematosus, with a high degree of disease activity (e.g. positive anti-dsDNA and low complement), despite standard therapy. The summary of product characteristics (SmPC) lists patient groups which have not been studied with belimumab, including severe active CNS lupus or severe active lupus nephritis. Use of belimumab is therefore not recommended to treat these conditions. Caution should be exercised if belimumab is co-administered with other B cell targeted therapy or intravenous cyclophosphamide, as it has not been studied in combination with these agents.

IMPORTANT SAFETY INFORMATION

The following safety information relates to the intravenous formulation of belimumab. It is not known if the subcutaneous formulation will have a similar safety profile.

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 BENLYSTA therapy in patients who develop a new infection while receiving BENLYSTA. The most frequent serious infections included pneumonia, urinary tract infection, cellulitis, and bronchitis.

MALIGNANCY

The impact of treatment with BENLYSTA on the development of malignancies is not known. As with other immunomodulating agents, the mechanism of action of BENLYSTA could increase the risk of malignancies.

HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS) AND INFUSION REACTIONS

Healthcare providers should be aware of the risk of hypersensitivity reactions, which may present as infusion reactions, and monitor patients closely. Some patients received premedication; however, there is insufficient evidence to determine whether premedication diminishes the frequency or severity of these reactions. Patients should be informed of the signs and symptoms of a hypersensitivity reaction and instructed to seek immediate medical care should a reaction occur.

In clinical trials, hypersensitivity reactions, including anaphylaxis, were reported. Manifestations 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.

In clinical trials, infusion-associated adverse events were 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.

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 BENLYSTA treatment is associated with increased risk for these events. Instruct patients to contact their healthcare provider if they experience new or worsening depression, suicidal thoughts, or other mood changes.

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 commonly reported adverse reactions (≥5%) were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, and pharyngitis.

OTHER IMPORTANT INFORMATION

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 BENLYSTA treatment and for at least 4 months after the last dose.

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 BENLYSTA group relative to black patients in the placebo group. In the Phase II trial, black patients (N=106) in the BENLYSTA group 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.