Novartis Reports Promising Phase 3 Results for Sjögren's Syndrome Drug Ianalumab

Novartis has unveiled encouraging results from two phase 3 clinical trials evaluating ianalumab, its investigational monoclonal antibody for the treatment of Sjögren's syndrome. The studies, known as Neptunus-1 and Neptunus-2, mark a significant milestone in the development of potential therapies for this autoimmune disease, which currently lacks approved systemic treatments.

Clinical Trial Outcomes

The Neptunus-1 and Neptunus-2 trials enrolled a total of 779 patients with Sjögren's syndrome. Both studies measured changes in disease activity using the EULAR Sjögren Syndrome Disease Activity Index (ESSDAI) at Week 48 compared to placebo.

In Neptunus-1, patients receiving monthly 300 mg doses of ianalumab experienced a mean ESSDAI score reduction of 6.4 from baseline, compared to a 5.1 reduction in the placebo group. This difference was statistically significant, albeit marginally, with a p-value of 0.0496.

Neptunus-2, a three-arm study, showed mixed results. While the quarterly dosing regimen failed to achieve statistical significance, monthly administration of ianalumab demonstrated a 6.5-point average drop in ESSDAI scores, compared to a 5.5-point decline in the placebo group (p-value 0.041).

A pooled analysis of monthly dosing data from both studies revealed a statistically significant advantage for ianalumab, with treated patients experiencing an average 6.5-point reduction in ESSDAI scores versus a 5.3-point drop for placebo (p-value 0.031).

Patient Benefits and Safety Profile

Beyond the primary endpoint, Novartis reported improvements in secondary measures crucial to Sjögren's syndrome management. Patients receiving ianalumab showed reductions in overall disease burden starting at Week 8, with notable improvements in dryness, pain, and fatigue.

The safety profile of ianalumab appears favorable, with comparable incidence of adverse events (AEs) and serious AEs across trial arms in both studies. One patient death was reported in the placebo arm of Neptunus-1.

Market Potential and Development Challenges

Novartis CEO Vasant Narasimhan expressed optimism about ianalumab's potential, stating, "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." He projected that ianalumab could become a multibillion-dollar product in the Sjögren's indication alone.

However, Narasimhan also acknowledged the challenges in drug development for Sjögren's syndrome, citing its heterogeneous nature and the need to control for placebo effects. "We've done everything we can in the design of the study to ensure that we control for placebo effects, that we power appropriately," he said during a Q3 earnings call.

The success of ianalumab in Sjögren's syndrome is particularly significant for Novartis following the company's decision to drop its anti-CD40 antibody iscalimab earlier this year due to concerns about its competitive profile. Ianalumab now stands as Novartis' primary candidate for addressing this unmet medical need.

As Novartis moves forward with ianalumab, the pharmaceutical industry will be watching closely to see if this promising therapy can navigate the regulatory pathway and potentially become the first approved systemic treatment for Sjögren's syndrome.