Novartis' Ianalumab Shows Breakthrough in Phase III Trials for Autoimmune Diseases

On August 11-12, Novartis consecutively announced three pieces of "good news" — its independently developed anti-BAFF-R monoclonal antibody Ianalumab (VAY736) achieved breakthrough results in three key Phase III clinical trials: including two global multicenter studies targeting active Sj?gren’s syndrome (NEPTUNUS-1, NEPTUNUS-2) and one study combining Eltrombopag for primary immune thrombocytopenia (ITP) treatment (VAYHIT2), all meeting their primary endpoints.

This series of achievements not only marks Ianalumab as a potential first approved targeted therapy for Sj?gren’s syndrome but also opens a new therapeutic pathway in the ITP field.

Ianalumab, acquired by Novartis for $2.9 billion from MorphoSys, is a fully human monoclonal antibody targeting B cell activating factor receptor (BAFF-R). It has a dual mechanism of depleting B cells and inhibiting BAFF-R, applicable for treating Sj?gren’s syndrome, immune thrombocytopenia (ITP), systemic lupus erythematosus (SLE), and other autoimmune diseases.

Sj?gren’s Syndrome: Global Multicenter Validation of Efficacy

Sj?gren’s syndrome is a chronic autoimmune disease characterized primarily by dry eyes and dry mouth, with a global prevalence of approximately 0.25%, over 90% of patients being female. The disease is often accompanied by extraglandular organ damage (such as lungs, kidneys, nervous system), and patients have a 4 to 44 times higher risk of lymphoma compared to the general population.

However, for a long time, Sj?gren’s syndrome lacked systemic treatment options. Clinical management was limited to symptom relief with artificial tears and saliva substitutes, unable to halt disease progression.

The NEPTUNUS-1 and NEPTUNUS-2 studies are randomized, double-blind, multicenter Phase III clinical trials (n=275). The former evaluated the efficacy and safety of Ianalumab (300mg, subcutaneous injection, once monthly) versus placebo in active Sj?gren’s syndrome, while the latter assessed Ianalumab (300mg, subcutaneous injection, once monthly or once every three months) versus placebo.

The primary endpoint for both studies was the change from baseline in the EULAR Sj?gren’s Syndrome Disease Activity Index (ESSDAI) score at week 52 between the Ianalumab and placebo groups. Results showed both studies met their primary endpoints, with significant improvement in disease activity for patients receiving Ianalumab. Additionally, Ianalumab demonstrated good tolerability and safety.

Novartis plans to present detailed data from these two studies at upcoming medical conferences and intends to submit a marketing application. If approved, Ianalumab will become the first targeted therapy for Sj?gren’s syndrome, filling an unmet clinical need.

ITP Treatment: Combination Therapy Opens New Track

Primary ITP is a rare disorder characterized by abnormally low platelet counts, putting patients at risk of bleeding, bruising, and chronic fatigue. Although current treatments (such as glucocorticoids and TPO receptor agonists) can temporarily increase platelet counts, long-term efficacy is limited with notable side effects.

The VAYHIT2 study is a randomized, double-blind, multicenter Phase III clinical trial evaluating the efficacy and safety of Ianalumab (3mg/kg or 9mg/kg, subcutaneous injection, once monthly) combined with Eltrombopag versus placebo plus Eltrombopag in primary ITP patients who failed prior corticosteroid first-line therapy.

The primary endpoint was time to treatment failure, defined as the time from randomization to any of the following: platelet count dropping below 30 G/L within 8 weeks post-randomization; need for rescue treatment within 8 weeks; initiation of new ITP therapy at any time; failure to taper or discontinue Eltrombopag; or death.

Results indicated significantly prolonged time to treatment failure in the Ianalumab group compared to placebo. Furthermore, at 6 months, the proportion of patients achieving sustained platelet count improvement was significantly higher in the Ianalumab group. Safety profile was consistent with prior studies, with no new safety signals observed.

Novartis expects to submit a marketing application for Ianalumab for ITP treatment in 2027, following the primary endpoint achievement of the ongoing Phase III VAYHIT21 study combining Ianalumab with corticosteroids.

Beyond These Indications

Ianalumab’s potential extends further. As a "star molecule" in Novartis’ autoimmune pipeline, its development spans lupus nephritis, systemic lupus erythematosus, hidradenitis suppurativa, systemic sclerosis, and other autoimmune indications. Phase III studies for SLE and lupus nephritis are underway.

The BAFF/BAFF-R pathway is a central target in B cell-mediated autoimmune diseases, but until now, only Belimumab (anti-BAFF antibody) has been globally approved for SLE treatment. Ianalumab’s dual mechanism of depletion and blockade offers a more thorough intervention on the BAFF pathway, promising to reshape autoimmune disease treatment paradigms.

Domestically, Betta Pharmaceuticals’ JH013 has received clinical approval and entered Phase I trials targeting Sj?gren’s syndrome and other diseases; Shijian Biotech’s ESG206 is in Phase I/II trials targeting immune thrombocytopenia and related conditions.