Belimumab

With litifilimab, Biogen is going after the type 1 interferon signature by inhibiting BDCA2.\n Biogen has bagged $250 million to advance a key pipeline prospect. Royalty Pharma is providing the cash to bankroll phase 3 development of a lupus candidate that Biogen has named in a bunch of assets with potential peak sales of $14 billion.The candidate, the anti-BDCA2 antibody litifilimab, is in phase 3 development in systemic and cutaneous lupus erythematosus (SLE/CLE). There is unmet need in both diseases. SLE patients have limited choices, with GSK’s Benlysta and AstraZeneca’s Saphnelo the only options, but that is rich pickings compared to CLE. Physicians have been waiting decades for an advance in the treatment of the cutaneous disease.Biogen believes litifilimab can address the unmet needs. But, with a pipeline of other programs—including two other lupus assets—to develop, the biotech has opted to seek external money to fund phase 3 trials in SLE and CLE.Royalty is providing the money, agreeing to drip-feed Biogen $250 million over six quarters in exchange for regulatory milestones and mid-single-digit royalties on annual worldwide sales. Royalty, a buyer of biopharmaceutical royalties, already receives a cut of the sales of Biogen’s Tysabri and Spinraza. The firm secured those royalties through deals with Ionis and Perrigo rather than directly from Biogen. Biogen has prioritized its pipeline under CEO Christopher Viehbacher, helping it cut R&D spending by 17% last year. The Royalty deal supports ongoing cost management while still allowing Biogen to attempt to bring litifilimab to market.Viehbacher talked up litifilimab’s prospects on an earnings call in October, including the asset among a clutch of candidates that the CEO said could collectively generate peak sales of $9 billion to $14 billion. CLE is an untapped opportunity. Litifilimab will face competition if it comes to market in SLE, potentially from Biogen’s own dapirolizumab, but Viehbacher sees room for multiple molecules.“This is a complex disease that affects different organs at a time,” Viehbacher said at the J.P. Morgan Healthcare Conference last month. “I think it\'s going to be a little like MS. You\'re really going to decide which product is best at which point in time for every patient. And so I don\'t think this is one product for the whole disease.”Dapirolizumab inhibits the CD40 ligand to reduce activation of B and T cells and downregulate interferon. With litifilimab, Biogen is going after the type 1 interferon signature by inhibiting BDCA2 in the plasma delta. The biotech is aiming to file for approval of litifilimab in SLE and CLE from 2027 to 2029.

Roche's Gazyva has excelled in a phase 3 trial of patients with lupus nephritis. When Gazyva was added to standard therapy, 46% of patients achieved complete renal response compared to 33% of those on standard care alone. While Roche’s Gazyva has been on the market for a dozen years and has won four approvals from the FDA, it is making a late push to gain a nod in what would be its most important indication—lupus nephritis.In September, Roche revealed success in the phase 3 Regency trial in lupus nephritis. Now the numbers are out, showing that 46.4% of patients who received Gazyva plus a standard therapy achieved complete renal response compared to 33.1% of patients on standard care alone, which consists of the immunosuppressive agent mycophenolate mofetil and glucocorticoids.Patients were evaluated at 76 weeks after receiving twice annual infusions of Gazyva.The primary endpoint results, which were characterized as statistically significant and clinically meaningful, were accompanied by improvements in complement levels and other biomarkers of disease activity and inflammation, Roche said.It did fall short, however, on secondary responses that looked at patients’ mean change in estimated glomerular filtration rates, death or renal-related events and overall renal responses. The results were revealed in the New England Journal of Medicine and presented at the World Congress of Nephrology in New Delhi, India.“The fact that nearly half of lupus nephritis patients achieved a complete renal response, together with clinically meaningful benefits observed consistently across subgroups, indicates superior disease control with Gazyva compared to standard treatment alone,” Levi Garraway, M.D., Ph.D., Roche’s chief medical officer and head of global product development, said in a release.Richard Furie, a rheumatologist at Northwell Health, added that it was “gratifying to see that patients who received (Gazyva) were not only more likely to achieve the desired outcome but were able to taper corticosteroids.”Roche has sent the data to the FDA and the European Medicines Agency (EMA) for regulatory review.Gazyva was first endorsed by the FDA in 2013 and has so far been cleared to treat various blood cancers. If greenlighted, Gazyva would become the first CD20-directed therapy approved in lupus nephritis. GlobalData projects that a nod could catapult sales of the monoclonal antibody to $1.7 billion by 2030. A dozen years ago, Roche failed to gain approval for Gazyva predecessor Rituxan in lupus nephritis as it came up short in a phase 3 trial. Despite this, doctors have been using Rituxan off-label based on real-world results. Lupus nephritis is a potentially life-threatening manifestation of the most common form of the disease lupus erythematosus (SLE) and has no cure. It involves kidney inflammation and primarily affects women, specifically women of color. Of the 1.7 million worldwide who have the disorder, a third will develop end-stage kidney disease within ten years, with dialysis and kidney transplants serving as their only available treatment options, according to Roche.GSK’s biologic blockbuster Benlysta, which was approved in 2011, is the dominant treatment for SLE. AstraZeneca’s biologic Saphnelo was approved in 2021 in the indication.