GSK receives FDA approval for a new self-injectable formulation of Benlysta (belimumab) for systemic lupus erythematosus

LONDON, July 21, 2017 /PRNewswire/ -- GSK announced today that the US Food and Drug Administration (FDA) has approved a new subcutaneous formulation of Benlysta (belimumab) for the treatment of adult patients with active, autoantibody-positive SLE who are receiving standard therapy. Systemic Lupus Erythematosus (SLE) is the most common form of lupus, a chronic, incurable autoimmune disease producing autoantibodies that can attack almost any system in the body. The approval marks the first subcutaneous self-injection treatment option for patients with SLE.

Experience the interactive Multichannel News Release here: https://www.multivu.com/players/English/8127551-gsk-benlysta-fda-approval/

After training from their health care provider, patients will be able to administer the medicine as a once weekly injection of 200mg, from either a single-dose prefilled syringe or from a single-dose autoinjector. This is the second formulation of Benlysta to be granted approval for SLE, adding to the existing intravenous (IV) formulation, approved in 2011, which is administered by healthcare professionals to patients as a weight-based dose of 10mg/kg, via a one-hour infusion in a hospital or clinic setting every four weeks (following an initial loading phase given on days 0, 14 and 28).

Vlad Hogenhuis, Senior Vice President, Head of Specialty Care, GSK said, "We are delighted with today's decision. Lupus can impact the lives of patients in many different ways with varied and often unpredictable symptoms. Since it launched in its IV form, thousands of patients worldwide have received treatment with Benlysta. The approval of the new injectable formulation will now provide an additional choice for patients, allowing them to self-administer their medicine at home rather than going to hospitals or clinics for their infusions."

The approval is based on data from the BLISS-SC phase III pivotal study of more than 800 patients with active SLE, which measured reduction in disease activity at Week 52 in patients receiving belimumab plus standard of care, versus those receiving placebo plus standard of care (assessed by SRI, a composite measure of efficacy in lupus).

Benlysta subcutaneous formulation will be available in specialty pharmacies in the US in late August.

Further regulatory submissions for the subcutaneous formulation of Benlysta are under review or planned in other countries during the course of 2017.

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 indicated 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.

Full US prescribing information including Medication Guide will be available in the near future at: gsksource.com. In the meantime, you may request a copy through GSK Communications.

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.

Benlysta subcutaneous formulation is currently not approved in the European Union.

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

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. Approximately 170,000-200,000 Americans live with SLE. It is a chronic, incurable autoimmune disease producing autoantibodies that can attack almost any system in the body.

Important Safety Information for belimumab
Please consult the full Prescribing Information for all the labelled safety information for Benlysta (belimumab).

BENLYSTA (belimumab):

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 intravenous clinical trials. Out of 2,133 patients in 3 clinical trials, a total of 14 deaths occurred during the placebo-controlled, double-blind treatment periods: 3/675 (0.4%), 5/673 (0.7%), 0/111 (0%), and 6/674 (0.9%) deaths in the groups receiving placebo, BENLYSTA 1 mg/kg, BENLYSTA 4 mg/kg, and BENLYSTA 10 mg/kg, respectively. Etiologies included infection, cardiovascular disease, and suicide.

In the controlled clinical trial of BENLYSTA administered subcutaneously (N = 836), a total of 5 deaths occurred during the placebo-controlled, double-blind treatment period (0.7% [2/280] of patients receiving placebo and 0.5% [3/556] of patients receiving BENLYSTA). Infection was the most common cause of death.

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 severe or chronic infections. Consider interrupting therapy with BENLYSTA in patients who develop a new infection while receiving BENLYSTA and monitor these patients closely.

In controlled clinical trials of BENLYSTA administered intravenously, serious infections occurred in 6.0% and 5.2% of patients receiving BENLYSTA and placebo, respectively. The most frequent serious infections included pneumonia, urinary tract infection, cellulitis, and bronchitis. Infections leading to discontinuation of treatment occurred in 0.7% and 1.0% of patients receiving BENLYSTA and placebo, respectively. Infections resulting in death occurred in 0.3% (4/1,458) and 0.1% (1/675) of patients receiving BENLYSTA and placebo, respectively. In the controlled trials of BENLYSTA administered subcutaneously (N = 836), serious infections occurred in 4.1% and 5.4% of patients receiving BENLYSTA and placebo, respectively.

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. Risk factors for PML include treatment with immunosuppressant therapies and impairment of immune function. Consider the diagnosis of PML in any patient presenting with new-onset or deteriorating neurological signs and symptoms and consult with a neurologist or other appropriate specialist as clinically indicated. In patients with confirmed PML, consider stopping immunosuppressant therapy, including BENLYSTA.

HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)
Acute hypersensitivity reactions, including anaphylaxis and death, have been reported in association 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. Limited data suggest that patients with a history of multiple drug allergies or significant hypersensitivity may be at increased risk.

In the controlled clinical trials of BENLYSTA administered intravenously, hypersensitivity reactions occurring on the day of the infusion were reported in 13% (191/1,458) and 11% (76/675) of patients receiving BENLYSTA and placebo, respectively. Anaphylaxis was observed in 0.6% (9/1,458) and 0.4% (3/675) of patients receiving BENLYSTA and placebo, respectively. Manifestations included hypotension, angioedema, urticaria or other rash, pruritus, and dyspnea.

Some patients (13%) received premedication, which may have mitigated or masked a hypersensitivity response. 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 and be prepared to manage anaphylaxis. In the event of a serious hypersensitivity reaction, discontinue BENLYSTA immediately and administer appropriate medical therapy. Patients should be monitored during and for an appropriate period of time after the intravenous administration of BENLYSTA. Patients receiving BENLYSTA 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.

In the controlled trial of BENLYSTA administered subcutaneously (N = 836), the incidence and severity of systemic hypersensitivity reactions were similar to those observed in the intravenous clinical trials.

INFUSION REACTIONS
In the controlled clinical trials, infusion reactions occurring on the day of the infusion were reported in 17% (251/1,458) and 15% (99/675) of patients receiving BENLYSTA and placebo, respectively.

Serious infusion reactions (excluding hypersensitivity reactions) were reported in 0.5% and 0.4% of patients receiving BENLYSTA and placebo, respectively. Serious infusion reactions included bradycardia, myalgia, headache, rash, urticaria, and hypotension. The most common infusion reactions occurring in ≥3% of patients receiving BENLYSTA were headache, nausea, and skin reactions.

Some patients (13%) received premedication, which may have mitigated or masked an infusion reaction; however, there is insufficient evidence to determine whether premedication diminishes the frequency or severity of these reactions. BENLYSTA should be administered by healthcare providers prepared to manage infusion reactions. The infusion rate may be slowed or interrupted if the patient develops an infusion reaction. Healthcare providers should be aware of the risk of hypersensitivity reactions, which may present as infusion reactions, and monitor patients closely.

DEPRESSION
In controlled clinical trials of BENLYSTA administered intravenously, serious psychiatric events were reported in 0.8% and 0.4% of patients receiving BENLYSTA and placebo, respectively. Serious depression was reported in 0.4% and 0.1% of patients receiving BENLYSTA and placebo, respectively. Two suicides were reported in patients receiving BENLYSTA. In the controlled trial of BENLYSTA administered subcutaneously, serious psychiatric events were reported in 0.2% of patients receiving BENLYSTA and in no patients receiving placebo. It is unknown if treatment with BENLYSTA 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.

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 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
Intravenous administration
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 least 1% 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%.

Subcutaneous administration
The safety profile observed for BENLYSTA administered subcutaneously was consistent with the known safety profile of BENLYSTA administered intravenously, with the exception of local injection site reactions, which occurred in 6.1% and 2.5% of patients receiving BENLYSTA and placebo, respectively.

OTHER IMPORTANT INFORMATION FOR BENLYSTA

USE IN SPECIFIC POPULATIONS
Pregnancy: There are insufficient data on use of BENLYSTA in pregnant women to establish whether there is drug-associated risk for major birth defects or miscarriage. Following an assessment of benefit versus risk, if prevention is warranted, women of childbearing potential should use effective contraception during treatment and for at least 4 months after the final treatment.

Lactation: There is no information available on the presence of belimumab in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for BENLYSTA and any potential adverse effects on the breastfed child from BENLYSTA or from the underlying maternal condition.

Black/African American Patients: In controlled clinical trials of BENLYSTA administered intravenously, SLE Responder Index-4 (SRI-4) response rates were lower for black/African American patients receiving BENLYSTA relative to black/African American patients receiving placebo.

In the controlled trial of BENLYSTA administered subcutaneously, SRI-4 response was slightly higher for black/African American patients receiving BENLYSTA relative to black/African American patients receiving placebo, but the treatment difference was not as great as that observed in the overall population. Use with caution in black/African American patients.

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.

GSK – 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.  For further information please visit www.gsk.com.

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 'Principal risks and uncertainties' in the company's Annual Report on Form 20-F for 2016.

Registered in England & Wales:
No. 3888792

Registered Office: 980 Great West Road
Brentford, Middlesex
TW8 9GS

SOURCE GSK