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FDA approves GSK’s BENLYSTA as the first medicine for adult patients with active lupus nephritis in the US

Approval builds on nearly 10 years of experience in lupus

GlaxoSmithKline plc (LSE/NYSE: GSK) announced the US Food and Drug Administration (FDA) has approved BENLYSTA (belimumab) for the treatment of adult patients with active lupus nephritis (LN) who are receiving standard therapy. Lupus nephritis is a serious inflammation of the kidneys caused by systemic lupus erythematosus (SLE), the most common form of lupus, which can lead to end-stage kidney disease, requiring dialysis or a kidney transplant. The approval extends the current indication in the US to include both SLE and LN for both the intravenous and subcutaneous formulations.

Dr. Hal Barron, Chief Scientific Officer and President R&D, GSK said: “Approximately 40% of patients with systemic lupus erythematosus develop lupus nephritis, which causes inflammation in the kidneys and can lead to end-stage kidney disease.  BENLYSTA is the first medicine approved to treat systemic lupus and adults with active lupus nephritis, an important treatment advance for patients with this incurable autoimmune disease.”

The FDA approval for adult patients with active LN follows a Breakthrough Therapy Designation and Priority Review and is based on the positive results of the BLISS-LN (Efficacy and Safety of Belimumab in Adult Patients with Active Lupus Nephritis) study and the unmet need in this patient population. The BLISS-LN study is the largest and longest phase 3 study conducted in active LN, involving 448 adult patients. The study met its primary endpoint demonstrating that a statistically significant greater number of patients achieved Primary Efficacy Renal Response (PERR) at two years (or 104 weeks) when treated with BENLYSTA plus standard therapy compared to placebo plus standard therapy in adults with active LN (43% vs 32%, odds ratio (95% CI) 1.55 (1.04, 2.32), p=0.0311). Statistical significance compared to placebo across all four major secondary endpoints was achieved, including Complete Renal Response and Time to Renal-Related Event or Death. The safety results are consistent with the known safety profile of BENLYSTA.

Dr. Richard Furie, Chief of the Division of Rheumatology and Professor at the Feinstein Institutes for Medical Research at Northwell Health and Lead Investigator of the BLISS-LN study, commented: “We have long aspired to enhance outcomes for patients with lupus nephritis. In the four decades I have been caring for people with lupus, we have not been able to achieve remission in more than just one-third of patients with lupus nephritis and, despite all of our efforts, 10% to 30% of patients with lupus kidney disease still progress to end-stage kidney disease. The data from the BLISS-LN study show that BENLYSTA added to standard therapy not only increased response rates over two years, but it also prevented worsening of kidney disease in patients with active lupus nephritis compared to standard therapy alone. Therefore, it is gratifying to see the rewards of decades of research.”

Dr. Brad Rovin, Director of the Division of Nephrology and Medical Director of the Center for Clinical Research Management at the Ohio State University Wexner Medical Center, commented: “The overarching goal in the management of patients with lupus nephritis is to delay the need for kidney replacement therapies, such as dialysis and transplantation. The BLISS-LN study not only demonstrated that the addition of BENLYSTA to standard therapy significantly increased the PERR, but also showed that patients had a 49% decrease in risk for experiencing a renal-related event. I’m encouraged by the progress we’re making in lupus nephritis.”

About the BLISS-LN study
BLISS-LN is a phase 3, 104-week, randomised, double-blind, placebo-controlled, post-approval commitment study to evaluate the efficacy and safety of intravenous (IV) BENLYSTA 10 mg/kg plus standard therapy (mycophenolate mofetil for induction and maintenance, or cyclophosphamide for induction followed by azathioprine for maintenance, plus steroids) compared to placebo plus standard therapy in adult patients with active LN. Active LN was confirmed by renal biopsy during screening visit using the 2003 International Society of Nephrology/Renal Pathology Society criteria within the past 6 months, and clinically active kidney disease requiring induction therapy.

For US Patients: Making our products affordable and accessible
GSK is actively involved in creating solutions that allow patients to have access to new scientific breakthroughs. We remain committed to helping patients access GSK medications and have a long history of providing patient assistance programs. Patients and healthcare professionals who need help with prescription coverage should visit www.BENLYSTA.com or call 1-877-4-BENLYSTA (1-877-423-6597) for eligibility information.

About lupus nephritis (LN)
Systemic lupus erythematosus (SLE), the most common form of lupus, 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. In lupus nephritis (LN), SLE causes kidney inflammation (swelling or scarring) of the small blood vessels that filter wastes in your kidney (glomeruli) and sometimes the kidneys, by attacking them like they would attack a disease[1]. LN can lead to end-stage kidney disease, which requires kidney dialysis or a transplant. Despite improvements in both diagnosis and treatment over the last few decades, LN remains an indicator of poor prognosis.[2],[3] Manifestations of LN include proteinuria, elevations in serum creatinine and the presence of urinary sediment.

About BENLYSTA (belimumab)
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. First approved in 2011, it is the first and only approved biologic for both SLE and LN in more than 50 years.

The following information is based on the US Prescribing Information for BENLYSTA in licensed indications only. Please consult the full Prescribing Information for all the labelled safety information for BENLYSTA.

INDICATION

BENLYSTA is indicated for patients aged ≥5 years with active, autoantibody-positive systemic lupus erythematosus (SLE) who are receiving standard therapy and patients aged ≥18 with active lupus nephritis who are receiving standard therapy. The subcutaneous (SC) formulation is approved for patients aged ≥18 years. BENLYSTA is not recommended in patients with severe active central nervous system lupus or in combination with other biologics.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATION
Previous anaphylaxis with BENLYSTA.

WARNINGS AND PRECAUTIONS
Serious Infections: Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents, including BENLYSTA. The incidence of serious infections was similar in patients receiving BENLYSTA versus placebo, whereas fatal infections occurred more frequently with BENLYSTA.  The most frequent serious infections in adults with SLE treated with BENLYSTA IV included pneumonia, urinary tract infection, cellulitis, and bronchitis. Use caution in patients with severe or chronic infections and consider interrupting therapy in patients with a new infection.

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. If PML is confirmed, consider stopping immunosuppressant therapy, including BENLYSTA.

Hypersensitivity Reactions (Including Anaphylaxis): Acute hypersensitivity reactions, including anaphylaxis (eg, hypotension, angioedema, urticaria or other rash, pruritus, and dyspnea) and death, have been reported, including in patients who have previously tolerated BENLYSTA. Generally, reactions occurred within hours of the infusion but may occur later. Non-acute hypersensitivity reactions (eg, rash, nausea, fatigue, myalgia, headache, and facial edema) typically occurred up to a week after infusion. Patients with a history of multiple drug allergies or significant hypersensitivity may be at increased risk. With BENLYSTA SC, systemic hypersensitivity reactions were similar to those in IV trials.

Healthcare providers (HCPs) should monitor patients during and after IV administration and be prepared to manage anaphylaxis; discontinue immediately in the event of a serious reaction. Premedication may mitigate or mask a hypersensitivity response. Advise patients about hypersensitivity symptoms and instruct them to seek immediate medical care if a reaction occurs.

Infusion Reactions: Serious infusion reactions (eg, bradycardia, myalgia, headache, rash, urticaria, and hypotension) were reported in adults. HCPs should monitor patients and manage reactions if they occur. Premedication may mitigate or mask a reaction. If an infusion reaction develops, slow or interrupt the infusion.

Depression and Suicidality:. In adult trials, psychiatric events were reported more frequently with BENLYSTA IV related primarily to depression-related events, insomnia, and anxiety; serious psychiatric events included serious depression and suicidality, including 2 completed suicides. No serious depression-related events or suicides were reported in the BENLYSTA SC trial. Before adding BENLYSTA, assess patients’ risk of depression and suicide and monitor them during treatment. Instruct patients/caregivers to contact their HCP if they experience new/worsening depression, suicidal thoughts, or other mood changes.

Malignancy: The impact of BENLYSTA on the development of malignancies is unknown; its mechanism of action could increase the risk for malignancies.

Immunization: Live vaccines should not be given for 30 days before or concurrently with BENLYSTA as clinical safety has not been established.

Use With Biologic Therapies: BENLYSTA has not been studied and is not recommended in combination with other biologic therapies, including B-cell targeted therapies.

ADVERSE REACTIONS:
The most common serious adverse reactions in adult SLE clinical trials were serious infections, BENLYSTA IV 6.0% (placebo 5.2%), some of which were fatal infections BENLYSTA IV 0.3% (placebo 0.1%). Adverse reactions occurring in ≥3% of adults and ≥1% more than placebo: nausea 15% (12%); diarrhea 12% (9%); pyrexia 10% (8%); nasopharyngitis 9% (7%); bronchitis 9% (5%);  insomnia 7% (5%); pain in extremity 6% (4%); depression 5% (4%); migraine 5% (4%); pharyngitis 5% (3%); cystitis 4% (3%); leukopenia 4% (2%); viral gastroenteritis 3% (1%).

In adult patients with active lupus nephritis, serious infections occurred in 14% of patients receiving BENLYSTA IV (placebo 17%), some of which were fatal infections, BENLYSTA 0.9% (placebo 0.9%).  Adverse reactions occurring in ≥3% of adults and ≥1% more than placebo were consistent with the known safety profile of BENLYSTA IV in SLE patients. 

Adverse reactions in pediatric patients aged ≥5 years receiving BENLYSTA IV were consistent with those observed in adults.

The safety profile observed for BENLYSTA SC in adults was consistent with the known safety profile of BENLYSTA IV with the exception of local injection site reactions.

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

Pregnancy Registry: HCPs are encouraged to register patients and pregnant women are encouraged to enroll themselves by calling 1-877-681-6296.

Lactation: No information is available on the presence of belimumab in human milk, the effects on the breastfed infant, or the effects on milk production. Consider developmental and health benefits of breastfeeding with the mother’s clinical need for BENLYSTA and any potential adverse effects on the breastfed child or from the underlying maternal condition.

Pediatric Use: The safety and effectiveness have not been established for BENLYSTA IV in SLE patients <5 years of age, and in active LN patients <18 years of age, and for BENLYSTA SC in SLE and LN patients <18 years of age.

GSK's commitment to immunology
GSK is focused on the research and development of medicines for immune-mediated diseases, such as lupus and rheumatoid arthritis, that are responsible for a significant health burden to patients and society. Our world-leading scientists are focusing research on the biology of the immune system with the aim to develop immunological-based medicines that have the potential to alter the course of inflammatory disease. As the only company with a biological treatment approved for adult and pediatric lupus, GSK is leading the way to help patients and their families manage this chronic, inflammatory autoimmune disease. Our aim is to develop transformational medicines that can alter the course of inflammatory disease to help people live their best day, every day.

About GSK
GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit www.gsk.com/about-us.

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 2019 and as set out in GSK’s “Principal risks and uncertainties” section of the Q3 Results and any impacts of the COVID-19 pandemic.
  

[1] National Kidney Foundation, Lupus and Kidney Disease (Lupus Nephritis).  Available at  https://www.kidney.org/atoz/content/lupus

[2] Gordon C, Hayne D, Pusey C, et al. European Consensus Statement on the Terminology used in the Management of Lupus Glomerulonephritis. Lupus 2009;18:257-26.

[3] Waldman M and Appel GB. Update of the Treatment of Lupus Nephritis. Kidney International 2006;70:1403-1412.