Iscalimab

Novartis is pulling back the curtain on late-stage Sjögren’s wins at this year’s American College of Rheumatology Convergence meeting.\n Novartis is pulling back the curtain on late-stage Sjögren’s wins, revealing an edge for its investigational monoclonal antibody ianalumab over placebo in both studies.“Clearly, with Sjögren\'s having no approved systemic therapies, and given the size of the patient population, there\'s an opportunity here to create a significant medicine,” Novartis CEO Vasant Narasimhan, M.D., said yesterday during a Q3 earnings call.In August, the Swiss pharma announced that it had scored a pair of phase 3 wins for ianalumab, a dual-mechanism, B-cell-depleting antibody, following its $2.9 billion acquisition of MorphoSys in 2024.The two studies, dubbed Neptunus-1 and Neptunus-2, enrolled 779 patients with the systemic autoimmune disease known as Sjögren’s syndrome. Neptunus-1 is a two-arm trial, while Neptunus-2 is a three-arm study.At the time, Novartis hailed the wins as the “first ever global phase 3 trials to demonstrate statistically significant reduction in disease activity for Sjögren’s disease,” though the pharma withheld details behind the victories.Now, Novartis has shared data at this year’s American College of Rheumatology Convergence meeting that demonstrates an edge over placebo and a favorable safety profile.Both studies’ primary endpoint measured the change from baseline in scores on an industry scale—called EULAR Sjögren Syndrome Disease Activity Index (ESSDAI)—at Week 48 versus placebo.In the two-arm trial, monthly administrations of ianalumab at 300 mg were tied to a mean ESSDAI score of 12.7 at 48 weeks, compared to 12.6 for those on placebo.Patients receiving ianalumab experienced an average score drop of 6.4 from baseline, compared to a decline of 5.1 score decline for the placebo group. That 1.3 difference was indeed statistically significant (p-value less than or equal to 0.05), though barely, with a p-value of 0.0496.For the three-arm study, 300 mg of the investigational therapy delivered once every three months failed to make a statistically significant difference in ESSDAI change from baseline against placebo.But monthly administration in Neptunus-2 demonstrated an average drop of 6.5 in ESSDAI scores compared to placebo\'s average decline of 5.5, a difference that was statistically significant (p-value of 0.041).In a pooled analysis of monthly dosing data from both studies, patients in the investigational treatment arms saw an average 6.5 drop in ESSDAI scores compared to placebo\'s 5.3 drop, a change that was also statistically significant (p-value of 0.031).During the Q&A portion of Novartis’ call yesterday, CEO Narasimhan highlighted challenges associated with drug development for Sjögren’s, pointing to the fact that it’s a heterogeneous disease, which means it can have several root causes.“We\'ve done everything we can in the design of the study to ensure that we control for placebo effects, that we power appropriately,” Narasimhan said. “We have the appropriate statistical analysis hierarchy that we\'ve included. FDA requested patient-reported outcomes, which I think will also be important for physicians.”“We\'ve done all of the steps needed to really give ourselves the best chance,” the CEO added. He also underscored the importance of not just the primary endpoint, but other measures for saliva production and fatigue that are impacted by Sjögren’s, which affects moisture-producing glands.Secondary endpoints “indicate symptom reduction and patient benefit beyond improvement in disease activity,” according to Novartis. The data show a reduction in overall disease burden starting at Week 8 as measured by a patient assessment, with improvements reported in dryness, pain and fatigue, as well.Ianalumab also demonstrated a favorable safety profile, Novartis said. The overall incidence of adverse events (AEs) and serious AEs were comparable across trial arms in both studies. One patient death was reported in the placebo arm of Neptunus-1.“I think we see ianalumab being a very significant medicine, if successful,” the CEO said yesterday. “We haven\'t guided to specific numbers yet, but I think certainly a multibillion-dollar potential medicine is what we would expect in just the Sjögren’s indication.”“If we can demonstrate, you know, that we move the needle for patient, patient, quality of life, we would expect a very significant medicine,” Narasimhan added yesterday. “So, we\'re excited about the readout.” The ianalumab readout comes in the same year that Novartis dropped its anti-CD40 antibody iscalimab after becoming skeptical of its competitive profile. That left ianalumab as Novartis’ only hope for the disease.Outside of Sjögren’s, ianalumab has faced its own clinical setbacks. Just this summer, Novartis reported that the B-cell-depleting antibody failed to hit the efficacy threshold in a phase 2 study for a painful skin condition called hidradenitis suppurativa.

Novartis hailed the win as the “first ever global phase 3 trials to demonstrate statistically significant reduction in disease activity for Sjögren\'s disease.”\n Novartis may have abandoned one Sjögren\'s syndrome asset this year, but it looks like the drugmaker has a winner on its hands with another candidate.The Swiss pharma had been evaluating ianalumab, a dual-mechanism, B-cell-depleting antibody that targets the protein BAFF-R, in a pair of phase 3 studies dubbed Neptunus 1 and 2, which in total enrolled 779 patients with the systemic autoimmune disease.Both studies hit their primary endpoint of demonstrating an improvement in disease activity as measured on the EULAR Sjögren\'s syndrome disease activity index at 52 weeks compared to placebo, Novartis announced in an Aug. 11 release. The drug was also well tolerated and demonstrated a favorable safety profile, according to the pharma.The company hailed the win as the “first ever global phase 3 trials to demonstrate statistically significant reduction in disease activity for Sjögren\'s disease.” For now, Novartis is holding back the data for a future medical conference, while referencing plans to take the results to global regulators with the aim of bringing the first targeted treatment for the autoimmune disease to market.“Sjögren\'s disease is a serious, progressive, systemic autoimmune disease, often unrecognized or misdiagnosed with a significant detrimental impact to quality of life, with very limited treatment options and an established unmet need,” Novartis Chief Medical Officer Shreeram Aradhye, M.D., said in the release.“Both phase 3 trials demonstrate that ianalumab improves disease activity in patients with Sjögren\'s disease,” Aradhye added. “These phase 3 studies mark a significant milestone. We look forward to engaging with health authorities to discuss these findings in the near future.”It’s a big win for Novartis, which started the year dropping its anti-CD40 antibody iscalimab after becoming doubtful of its competitive profile. That left ianalumab as Novartis’ last and best hope for the disease.Ianalumab had already shown \"meaningful differences in patients with this very difficult-to-treat disease” in phase 2, Novartis executives pointed out at the time.Iscalimab was only the latest Big Pharma prospect to fail to make the grade in Sjögren\'s. Last year, Sanofi crossed off Sjögren’s from the list of targeted indications for its CD40L monoclonal antibody frexalimab after seeing phase 2 efficacy data, while, more recently, Kiniksa Pharmaceuticals ended work on its own Sjögren\'s prospect abiprubart. While Novartis had always sounded positive about the potential of ianalumab in the automimmune disease, the therapy has faced its own clinical setbacks. Only last month, the company reported that the B-cell-depleting antibody had failed to hit the efficacy threshold in a phase 2 study for a painful skin condition called hidradenitis suppurativa.Ianalumab\'s story begins with Novartis’ collaboration with MorphoSys, before the Big Pharma went on to buy the biotech last year. The therapy is also being investigated for other B cell-driven autoimmune diseases like immune thrombocytopenia, systemic lupus erythematosus, lupus nephritis, warm autoimmune hemolytic anemia and diffuse cutaneous systemic sclerosis.