GlaxoSmithKline plc (GSK) and Human Genome Sciences, Inc. announced that the US Food and Drug Administration (FDA) has approved Benlysta (belimumab) for the treatment of adult patients with active, autoantibody-positive Systemic Lupus Erythematosus (SLE) who are receiving standard therapy.

The US label includes the following 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, and has not been studied in combination with other biologics or intravenous cyclophosphamide. Use of belimumab is therefore not recommended in these situations.

Moncef Slaoui, PhD, chairman, GSK Research and Development, said, “The approval of Benlysta is an important step for appropriate lupus patients. Patients have been waiting for new treatment options to help manage this chronic disease. We look forward to working together with HGS to bring this new medicine to patients in the US.”

“We and GSK are honoured to have the opportunity, with the approval of FDA, to bring Benlysta forward in the United States as the first new drug for systemic lupus in more than 50 years,” said H. Thomas Watkins, president and chief executive officer, HGS. “We expect to have this novel therapy available to physicians and patients within about two weeks, and our entire organisation looks forward to the positive impact we hope this new therapy will have for patients with systemic lupus.”

Benlysta (belimumab) is contraindicated in patients who have had anaphylaxis with belimumab. There were more deaths reported with belimumab than with placebo during the controlled period of the clinical trials. No single cause of death predominated. Etiologies included infection, cardiovascular disease, and suicide.

Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents, including belimumab. In controlled clinical trials, serious infections occurred in 6.0% of patients treated with belimumab and in 5.2% of patients who received placebo. The most frequent serious infections included pneumonia, Urinary Tract Infection (UTI), cellulitis, and bronchitis. The most frequent infections (=5%) were upper respiratory tract infection, UTI, nasopharyngitis, sinusitis, bronchitis, and influenza.

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

Hypersensitivity reactions were reported in 13% of patients receiving belimumab and 11% of patients receiving placebo, and included anaphylaxis (0.6% with belimumab and 0.4% with placebo).  Infusion-associated adverse events were reported in 17% of patients receiving belimumab and 15% of patients receiving placebo.  Serious infusion reactions included bradycardia, myalgia, headache, rash, urticaria, and hypotension.  The most common infusion reactions (>3%) were headache, nausea, and skin reactions.

Psychiatric events (primarily depression, insomnia, and anxiety) were reported more frequently with belimumab (16%) than with placebo (12%). Serious psychiatric events, serious depression and two suicides were also reported (0.8% for belimumab and 0.4% for placebo). It is unknown if belimumab treatment is associated with increased risk for these events.

The most commonly reported adverse reactions (³5%) with Benlysta were nausea, diarrhea, pyrexia, nasopharyngitis, bronchitis, insomnia, pain in extremity, depression, migraine, and pharyngitis.

Benlysta (belimumab) is the first in a new class of drugs called BLyS-specific inhibitors. Belimumab blocks the binding of soluble BLyS, a B-cell survival factor, to its receptors on B cells. Belimumab does not bind B cells directly, but by binding BLyS, belimumab inhibits the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells. BLyS is a naturally occurring protein which was discovered by HGS in 1996.

Benlysta is made available as a lyophilised powder in single-use vials for intravenous infusion only and must be reconstituted and diluted by a healthcare professional prior  to administration.

GSK submitted a Marketing Authorisation Application (MAA) for Benlysta to the European Medicines Agency (EMA) in June 2010. Regulatory applications have also been submitted and are currently under consideration in Canada, Australia, Switzerland, Russia, Brazil and The Philippines.

HGS and GSK are developing belimumab under a definitive co-development and co-commercialisation agreement entered into in 2006. Under the agreement, HGS had responsibility for conducting the belimumab Phase III trials, with assistance from GSK. The companies share equally in Phase III/IV development costs, sales and marketing expenses, and profits of any product commercialised under the current agreement.

GlaxoSmithKline – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer.

Human Genome Sciences exists to place new therapies into the hands of those battling serious disease.