GSK Plans Benlysta Expansion In Lupus Nephritis Based On Successful Phase III
Executive Summary
Benlysta was an early pioneer in systemic lupus erythematosus, but GSK now plans to expand the drug into the acute area, active lupus nephritis, with a filing in 2020.
Nearly eight years after GlaxoSmithKline PLC's Benlysta (belimumab) became the first drug approved by the US Food and Drug Administration for lupus, the company is looking to expand the drug's indication to a substantial new subset of patients in the acute phase of the disease, even as the late-stage development space is heating up.
The company announced on 18 December positive data from a Phase III trial testing Benlysta in patients with lupus nephritis, the acute inflammation of the kidneys caused by chronic systemic lupus erythematosus (SLE)
Even today Benlysta remains the only drug approved by FDA for lupus, despite lots of development work in the space. (Also see "Lupus Market Snapshot: There's No Debate It's A Blockbuster Opportunity" - Scrip, 10 Aug, 2017.)
The BLyS-specific inhibitor was hailed as a major milestone when it was approved for SLE in 2011 with big blockbuster commercial expectations, but the drug's efficacy was viewed as moderate in the commercial market and the product ultimately became far more niche than GSK and the initial developer Human Genome Sciences Inc. had envisioned.
Nonetheless, Benlysta has been growing double digits in recent years, powered by a newer, more convenient subcutaneous formulation and patient and physician experience.
(Also see "Benlysta Is Niche, But Growing, So GSK's Not Giving Up On Lupus" - Scrip, 7 Aug, 2017.) Sales of Benlysta grew 35% in the third quarter to £172m, partly driven by the launch of a subcutaneous version.
Now GSK has an eye on expanding the drug to a substantial new patient population, those with active lupus nephritis (LN). If approved, it would represent a new target market for Benlysta because the drug's labeling currently includes a limitation of use in the indications section highlighting that the drug has not been studied in patients with active lupus nephritis.
"There are currently no medicines approved for severe active lupus nephritis by FDA, and we will be working fast and furiously to ensure we can bring Benlysta to these patients so Benlysta can treat the full spectrum of SLE, including those most severe patients with lupus nephritis," senior VP-US specialty pharma business Sheri Mullen said in an interview.
The company said it is on track to file for a labeling expansion in the first half of 2020. The timeline would position it in a tight race with Aurinia Pharmaceuticals Inc. to secure an approval in LN.
There are about 330,000 patients in the US with SLE, including those that are diagnosed and undiagnosed, according to GSK. There has been a lot of discrepancy about lupus’ prevalence given poor rates of diagnosis, and they have been estimated by the Lupus Foundation of America to be much higher, more than 1 million. That's one reason GSK has previously said the pre-approval blockbuster forecasts for Benlysta were overblown.
Of the roughly 330,000 patients GSK estimates have SLE, about 60% of patients experience LN, and about half of those patients are the most severe patients with biopsy-documented severe active lupus, Mullen said.
"That is why this study is so important, because this BLISS-LN study met the primary endpoint and all the secondary endpoints in these most severe patients," she added.
The BLISS-LN study, a post-approval commitment in the US and Europe, enrolled 448 patients and measured treatment with belimumab plus standard therapy compared to placebo plus standard therapy in adults with active LN. The study met the primary endpoint, showing a statistically significant greater number of patients achieved Primary Efficacy Renal Response (PERR) over two years in the belimumab arm versus placebo (43% vs 32%).
Belimumab also demonstrated statistical significance compared to placebo across all four major secondary endpoints: Complete Renal Response (CRR) after two years, considered the most stringent measure of renal response; Ordinal Renal Response (ORR) after two years; PERR after one year; and the time to death or renal-related event. CRR was defined as estimated Glomerular Filtration Rate (eGFR)of no more than 10% below the pre-flare value or within normal range. PERR was defined as 60mL/min/1.73m2 or greater or no decrease in eGFR from pre-flare of more than 20%; and urinary protein creatinine ratio (uPCR) of 0.7 or less.
The study tested the intravenous version of Benlysta, which is dosed every two weeks for the first three doses and then every four weeks. The subcutaneous version is dosed weekly. GSK said it would discuss the data and the dosing options with FDA.
Benlysta may not have the lupus market to itself for long, but Mullen said GSK welcomes new competition and expects to remain a leader.
"There has been such a gap in this space for these lupus patients, I do believe new treatment options are needed across the board," Mullen said. "We more treatment options for SLE and for patients with the most difficult LN, it will raise all tides."
"Benlysta stands strong on the wealth of clinical evidence and experience in research and development and commercialization since 2011," she added.
Aurinia's voclosporin in Phase III and Roche's CD20 blocker Gazyva (obinutuzumab) in Phase II are two of the drugs in advanced development. Aurinia recently reported positive Phase III data on voclosporin based on renal response measures in LN and plans to file for FDA approval in the first half of 2020. (Also see "Aurinia Closing In On Lupus Nephritis With Voclosporin" - Scrip, 5 Dec, 2019.) Meanwhile, AstraZeneca PLC announced positive Phase III data on the interferon blocker anifrolumab in SLE. (Also see "AstraZeneca Closer To Filing Anifrolumab For Lupus " - Scrip, 12 Nov, 2019.) Biogen Inc. recently reported positive Phase II data on its antibody targeting blood dendritic cell antigen 2 (BCDA2), which also blocks type I interferon in SLE.