GSK receives approval for Benlysta in Japan for the treatment of systemic lupus erythematosus

Issued: London, UK

GSK announced today that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Benlysta (belimumab) for the treatment of adult patients with systemic lupus erythematosus (SLE) who are inadequate responders to existing therapies. Benlysta is for use as an add-on therapy in autoantibody positive SLE patients. 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.

Benlysta is a human monoclonal antibody that works by selectively targeting B-lymphocyte stimulator (BLyS), an important factor in SLE. It binds to BLyS directly, which reduces B-cells and helps decrease the immuno-inflammation observed in SLE patients.

The medicine will be available for patients in two formulations, as an injection, for intravenous (IV) use and an injection, for subcutaneous (SC) use. The IV formulation is administered by healthcare professionals to patients as a weight-based dose of 10mg/kg, via a one-hour infusion in a hospital or clinical setting every four weeks (following an initial loading phase given at Weeks 0, 2 and 4). The subcutaneous formulation can be administered as a once weekly injection of 200mg, from either a single-dose prefilled syringe or from a single-dose autoinjector.

Vlad Hogenhuis, Senior Vice President, Head of Specialty Care, GSK said, “Patients living with SLE have limited treatment choices available and may have to endure the associated side effects these can cause. SLE symptoms are broad, variable and unpredictable in their intensity, which means an individualised treatment approach is needed. Benlysta, in its IV form, has been used to treat thousands of patients worldwide and with today’s approval of two formulations, we are delighted that we can now provide an important new treatment option to physicians and SLE patients in Japan.”

The approval is based on data from two recent pivotal Phase III studies (Northeast Asia IV study and BLISS-SC study) and also efficacy and safety data from two earlier global BLISS-IV Phase III studies (BLISS-52, BLISS-76). The studies measured reduction in disease activity at Week 52 in patients with active SLE receiving belimumab plus standard of care, versus those receiving placebo plus standard of care (assessed by SRI, a composite measure of efficacy in lupus). The pivotal Northeast Asia study (Japan, China and South Korea) evaluated the efficacy and safety of belimumab administered intravenously every four weeks in 705 patients and the BLISS-SC study evaluated subcutaneous belimumab administered weekly in 836 patients. The 2 earlier BLISS-IV global trials evaluated the efficacy and safety of belimumab administered intravenously in a total of 1,684 patients.

Benlysta IV 10 mg/kg is also licensed for use in the US, EU and more than 70 countries worldwide. Benlysta subcutaneous formulation was approved for use in the US in July 2017 and further regulatory submissions 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.

Japanese Drug Information for Benlysta will be available soon at https://www.healthgsk.jp/. Prior to the label being posted online, a copy may be requested from one of the GSK Media or Investor Relations contacts listed in the “GlaxoSmithKline enquiries” section at the end of this document.

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. There are an estimated 60,000 registered patients living with SLE in Japan. 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 for belimumab
The following Important Safety Information (ISI) is based on a summary of the Japanese Drug Information for Benlysta (belimumab). Please consult the full Drug Information for all the labelled safety information for Benlysta.

Precautions for the Indication
Use BENLYSTA as an add -on therapy in patients with disease activity remaining despite previous treatment with SLE drugs, e.g. steroids, immunosuppressive agents. Use in patients with SLE confirmed to be autoantibody positive.

Efficacy and safety have not been evaluated in SLE patients with severe lupus nephritis or central nervous system lupus.

The efficacy and safety of Benlysta has not been evaluated in combination with other biologic drug or cyclophosphamide intravenous injection.

Warning
Benlysta must not be used in patients unless its potential clinical benefit justifies the potential risks and must be given by doctors with sufficient SLE therapeutic knowledge/experience at medical institutions with relevant emergency units in handling infections. Prior to starting therapy, the efficacy and risks must be explained to the patient, including that Benlysta is not intended as a radical cure.

BENLYSTA may increase the risk of infection, and may also reactivate tuberculosis in patients with a history of tuberculosis. Serious infections:  Fatal infection such as opportunistic infection including sepsis, pneumonia, and fungal infection have been reported. Patients should be carefully monitored for possible development/exacerbation of infection and instructed to contact the attending doctor immediately upon discovery of signs and symptoms of infection following administration of Benlysta.

Cases of malignant tumours have been reported, although, causal relation with BENLYSTA is unknown.

Before using BENLYSTA, adequately consider using other medication for treatment of systemic lupus erythematous such as steroids, immunosuppressive agents.

Contraindications
BENLYSTA is contraindicated in patients with a history of hypersensitivity to belimumab or any of the excipients and in patients with serious infection or active tuberculosis.  (BENLYSTA may worsen the symptoms).

Precautions
Hypersensitivity reactions in association with BENLYSTA have been reported, which can be serious or fatal. Delayed-onset of hypersensitivity reactions may occur.  Patients should be advised to see their physician if signs and symptoms of hypersensitivity reactions are experienced, or if any signs and symptoms of infection occur.

BENLYSTA should be administered with caution in patients with infection or suspected infection, patients with a history of tuberculosis, and in patients with depression or depressed state or a history of these, and in patients with a history of suicide ideation or suicide attempt.

Prior to the commencement of BENLYSTA therapy, the presence/absence of tuberculosis and hepatitis virus infections should be confirmed.

Tuberculosis should be confirmed on interview and chest X-ray; in addition, an interferon γ release assay, and as required a chest CT should be performed. An antituberculosis drug should be considered in certain circumstances. Patients should be carefully monitored and should contact the doctor promptly upon occurrence of suspected tuberculosis symptoms (e.g. persistent cough and pyrexia). BENLYSTA should not be used if active tuberculosis is confirmed.

When Benlysta is administered to hepatitis B virus carriers/persons with a history of hepatitis B infection, attention must be paid to the appearance of signs and symptoms of virus reactivation through monitoring of hepatic function test values and hepatitis virus markers

Live vaccines should not be given during treatment with BENLYSTA.

Adverse reactions
In multinational phase III studies, adverse reactions were reported in 28.9% (IV formulation) and 31.1% (SC formulation) of patients who received BENLYSTA.  The most common adverse reactions for the IV Benlysta formulation included upper respiratory tract infections, herpes zoster, nasopharyngitis, bacterial urinary tract infection and cough; for the SC Benlysta formulation it included: viral upper respiratory infections, bacterial urinary tract infections and nasopharyngitis.

In two overseas phase III studies in the IV formulation, adverse reactions were reported in 38.1% (study BEL110751) and 36.2% (study BEL110752) of patients who received BENLYSTA. The most common adverse reactions were upper respiratory tract infection, nausea and sinusitis in BEL110751 and headache, urinary tract infection and pharyngitis in BEL110752.

Serious hypersensitivity may occur (incidence was 0.6% for IV and unknown for SC). This includes shock or anaphylaxis.  Delays in the onset of these symptoms have also been observed and these delayed-type reactions may include rash, nausea, fatigue, myalgia, headache and facial edema.  Patients should be closely monitored and if any abnormality is observed, BENLYSTA should be discontinued immediately and appropriate measures should be taken.

Infections may occur (incidence was 20% for IV and 18.7% for SC). These include serious infections such as pneumonia, sepsis and tuberculosis.

Progressive multifocal leukoencephalopathy (PML) may occur (incidence unknown). The patients condition should be carefully monitored during and after Benlysta treatment. Administration should be discontinued and appropriate measures taken if PML symptoms appear.

Interstitial pneumonia may occur (incident was 0.1% for IV and unknown for SC). Patients should be made aware of respiratory symptoms. If any abnormality is observed, patients should be immediately assessed by chest X-ray, chest CT and arterial blood gas analysis. BENLYSTA should be discontinued and take appropriate treatment considering differential diagnosis with Pneumocystis pneumonia. If a patient has a history of interstitial pneumonia, the patient should be carefully monitored by periodic interviews.

Japanese Drug Information will be available soon at http://glaxosmithkline.co.jp/healthcare/. Prior to the label being posted online, a copy of the label may be requested from one of the GSK Media or Investor Relations contacts listed in the “GlaxoSmithKline Inquiries” section at the end of this document.

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