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.