In an interview with PharmaShots, Steve Bradford, Vice President, Medicines Commercialization Leader at GSK shed light on the US FDA’s approval of Benlysta as the first and only approved treatment for both lupus and adult patients with active LN who are receiving standard therapy.
- The US FDA has approved GSK’s Benlysta (belimumab) as the first and only approved treatment for both lupus and adult patients with active LN who are receiving standard therapy
- With Benlysta as the first and only approved biologic for lupus in 50+ years, this approval builds on 10 years of clinical evidence in lupus and results of the largest clinical trial in LN
- Benlysta is a BLyS-specific inhibitor and a mAb that binds to soluble BLyS. 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
Tuba: Tell us more about BENLYSTA’s approval in active lupus nephritis (LN) and how BENLYSTA works?
Steve: On behalf of GSK, I’m proud that on December 16, 2020, the US Food and Drug Administration (FDA) approved BENLYSTA (belimumab) for the treatment of adult patients with active lupus nephritis (LN) who are receiving standard therapy. First approved in 2011 for systemic lupus erythematosus (SLE), BENLYSTA is the first and only approved treatment for both SLE and LN in more than 50 years.
The approval of BENLYSTA in adults with active LN who are receiving standard therapy is a profound advancement for the lupus community, as now healthcare professionals have a treatment option that works across the spectrum of SLE and LN and can further improve outcomes for those living with the disease.
LN, one of the most common organ manifestations of lupus, can lead to end-stage kidney disease (ESKD), 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.
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.
Tuba: Can you discuss the epidemiology of LN?
Steve: At least 5 million people worldwide have a form of lupus, and as the most common form of the disease, SLE accounts for approximately 70% of all cases. In the US, approximately 330,000 people have SLE; of those, LN can occur in up to 40% of adults with SLE. Although women are disproportionately affected by SLE, men with SLE are more likely to develop LN than women with SLE.
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. In LN, SLE causes kidney inflammation (swelling or scarring) of the small blood vessels that filter waste in your kidney (glomeruli) and sometimes the kidneys, by attacking them like they would attack a disease. LN can lead to ESKD, which could require dialysis or a transplant.
The goal of treating lupus nephritis is to achieve a renal response, prevent relapse/flares and progression to ESKD while minimizing treatment toxicity. Despite improvements in both diagnosis and treatment over the last few decades, LN remains an indicator of poor prognosis. Historically, only 40-50% of LN patients have responded to standard therapies for the disease. Standard therapies did not help as many patients achieve a renal response.
With this new indication for BENLYSTA, GSK has the potential to address a significant unmet medical need for the lupus community. Healthcare professionals now have a treatment option that may help improve the lives of people living with this potentially fatal condition.
Tuba: Is the company planning to explore the potential of BENLYSTA in other indications? If yes, what are those indications?
Steve: Due to the unmet need of patients with SLE and GSK’s focus on research and development of medicines for people living with lupus, we continue to investigate SLE in various populations and have initiated post-approval research programs to look at different ways of treating. Approximately 80% of patients with SLE who may be eligible for a biologic are not currently receiving one. So, there is tremendous opportunity for growth overall.
GSK has a long history in lupus R&D, we are extremely proud of what we have been able to deliver through the BENLYSTA program. We’ve now had five consecutive successful pivotal trials. In addition to the BLISS-LN study, which was the basis of the current Supplemental Biologics License Application (sBLA) and approval, in the past two years alone the immense BENLYSTA lifecycle program delivered results for the largest study ever conducted in lupus (BASE), our pediatric study, (PLUTO), which resulted in indications in children five and older in US, Europe, Japan and China – the first of their kind; our study in the black race (EMBRACE), and real-world evidence on the delayed progression of long term organ damage. Additionally, we have an ongoing Phase 3 trial, BLISS-BELIEVE, evaluating BENLYSTA plus a single cycle of Rituximab (RITUXAN), which is aimed at demonstrating sustained disease control while minimizing immuno-suppressants and steroids.
Tuba: Please explain the Phase 3 study supporting the efficacy of BENLYSTA in adults with active LN.
Steve: BLISS-LN is a Phase 3, 104-week, randomized, double-blind, placebo-controlled, study to evaluate the efficacy and safety of BENLYSTA 10 mg/kg IV 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.
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.
Tuba: Are you evaluating the efficacy of BENLYSTA in infants and pregnant women?
Steve: BENLYSTA is currently FDA approved for the treatment of patients aged 5 years and older with active, autoantibody-positive SLE who are receiving standard therapy.
We have a registry established to monitor maternal-fetal outcomes of pregnant women exposed to BENLYSTA. Healthcare professionals are encouraged to register patients and pregnant women are encouraged to enroll themselves by calling 1-877-681-6296.
Tuba: What are the other targeted countries for seeking approval in LN?
Steve: For general SLE, BENLYSTA IV is approved in more than 70 countries, with the subcutaneous formulation approved in more than 40 countries. We have submitted applications for adults with active LN in the EU (EMA), China (CDE), Canada, Brazil, Switzerland, Russia, and Taiwan with more to come in the coming months.
Tuba: How does the addition of BENLYSTA to the standard therapies help people with lupus or LN?
Steve: Historically, only 40-50% of LN patients achieve a renal response with standard therapies. Even when the renal response is achieved, it’s difficult to maintain, and up to a third of patients experience a renal flare or relapse. Significantly more patients on BENLYSTA received renal response versus standard therapy alone and showed a significantly reduced risk of kidney worsening.
This approval builds on nearly 10 years of experience in lupus post initial approval. With its deep history and heritage in lupus R&D, GSK is committed to improving the lives of patients living with the disease with therapeutics.
Tuba: Do we have few details about BENLYSTA Cares? Are there any other patient support/adherence programs running/planned by GSK?
Steve: BENLYSTA Cares is a US patient support program that provides financial support, a phone helpline, injection support, and education to provide patients with the confidence they need to start BENLYSTA or BENLYSTA subcutaneous. For more information, please contact 1-877-4-BENLYSTA or BENLYSTA.com.
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.
Tuba: Are you planning for any digital initiative to improve the lives of patients with LN and other autoimmune diseases?
Steve: GSK is continuing to expand its patient marketing for BENLYSTA in all media channels, including social, web search, point-of-care and targeted TV.
One initiative that we’re particularly proud of is our Us in Lupus program, which is a 12-week virtual education program for those newly diagnosed with SLE and now LN, providing resources such as education, a patient journal, and symptoms tracker to help people have honest and open conversations with their healthcare team. Through the www.UsInLupus.com and corresponding Facebook community, we hope this also serves as a reminder that those living with lupus are not alone, and that others living with lupus have found help, self-confidence, and strength.
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Steve Bradford serves as the Vice President, Global Medicine Commercialization Lead, Benlysta of GSK. Steve started at GSK in September of 2018 and currently resides in the Raleigh-Durham, North Carolina Area.