Ianalumab for the Treatment of Patients with Sjögren’s Disease 2026 Mariette

[Jaybee00]

Ianalumab for the Treatment of Patients with Sjögren’s Disease​

Authors: Xavier Mariette, M.D., Ph.D. https://orcid.org/0000-0002-4244-5417, ThomasGrader-Beck, M.D., Stephanie Finzel, M.D., ElenaSchiopu, M.D., Athena Papas, Ph.D., ValerieDevauchelle-Pensec, M.D., Ph.D., Monika Sopala, Ph.D., +24

Abstract​

BACKGROUND​

Sjögren’s disease is a complex, systemic autoimmune disease with no approved targeted therapies. Ianalumab is an IgG1 monoclonal antibody with a dual mechanism of action, depleting B cells through antibody-dependent cellular cytotoxicity and inhibiting B-cell activation and survival through blockade of B-cell activating factor receptor.

METHODS​

We conducted two 52-week, double-blind, randomized, placebo-controlled trials involving patients with active Sjögren’s disease. Patients in the NEPTUNUS-1 trial were assigned in a 1:1 ratio to receive subcutaneous ianalumab (300 mg monthly) or placebo; patients in the NEPTUNUS-2 trial were assigned in a 1:1:1 ratio to receive 300 mg of ianalumab monthly or every 3 months or placebo. The primary end point was the change from baseline in the score on the European Alliance of Associations for Rheumatology (EULAR) Sjögren’s Syndrome Disease Activity Index (ESSDAI) at week 48 (scores range from 0 to 123, with higher scores indicating greater disease activity). The first key secondary end point in the hierarchical plan for the NEPTUNUS-1 trial was an ESSDAI response (≥5-point reduction) at week 48; for the NEPTUNUS-2 trial, it was the change from baseline in the score on the Sjögren’s Syndrome Symptom Diary (SSSD) or EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) at week 48.

RESEARCH SUMMARY

Ianalumab for the Treatment of Patients with Sjögren’s Disease​

RESULTS​

Overall, 275 patients underwent randomization in the NEPTUNUS-1 trial (ianalumab monthly, 137 patients; placebo, 138 patients) and 504 in the NEPTUNUS-2 trial (ianalumab monthly, 168 patients; ianalumab every 3 months, 167 patients; and placebo, 169 patients). In both trials, ianalumab monthly led to a significantly greater decrease in the ESSDAI score at week 48 than placebo, with a between-group difference of −1.3 points (95% confidence interval [CI], −2.6 to 0.0; P=0.0496) in NEPTUNUS-1 and −1.0 points (95% CI, −2.0 to 0.0; P=0.04) in NEPTUNUS-2. No significant differences in the incidence of an ESSDAI response or in the change from baseline in SSSD or ESSPRI scores were observed at week 48. The incidence of serious adverse events was similar with ianalumab and placebo. Nonserious local injection-site and systemic injection-related reactions were more common in the ianalumab groups.

CONCLUSIONS​

In these two trials involving patients with active Sjögren’s disease, ianalumab at a dose of 300 mg monthly resulted in a significantly greater decrease in disease activity at week 48 than placebo, although there were no significant differences in the incidence of an ESSDAI response or in the change from baseline in SSSD or ESSPRI symptom scores. (Funded by Novartis Pharma; NEPTUNUS-1 and NEPTUNUS-2 ClinicalTrials.gov numbers, NCT05350072and NCT05349214, respectively.)

https://www.nejm.org/doi/full/10.1056/NEJMoa2601088

 

[Jaybee00]

I guess folks aren’t so impressed

Ianalumab's Road to Approval for Sjogren's Looks Bumpier​

Key Takeaways​

• Sjögren's disease currently has no approved targeted therapies, but recent research on the role of B cells in driving the condition led to a biologic agent, ianalumab, that inhibits B-cell activating factor.
• Two parallel phase III trials tested the drug in a total of 779 Sjögren's disease patients, with change from baseline in so-called ESSDAI scores as the primary endpoint.
• Published findings indicate that it was met, but less impressive results for secondary outcomes raise questions about its true efficacy; ianalumab's sponsor has commenced a new phase III trial.

Ianalumab's Road to Approval for Sjogren's Looks Bumpier

Pivotal studies, now published, yield mixed results; new phase III trial now underway

www.medpagetoday.com

 

[Utsikt]

For assessment of the primary end point, we calculated that a sample size of approximately 268 patients (134 per group) in the NEPTUNUS-1 trial would provide the trial with a power of 82%, at a two-sided alpha level of 5%, and a sample size of 489 (163 per group) in the NEPTUNUS-2 trial would provide the trial with a power of 83%, at a two-sided alpha level of 5%, to show the superiority of ianalumab over placebo in terms of change from baseline (under the assumption of a between-group difference of 2 points) in the ESSDAI score at week 48.

The protocol is 800+ pages, so I’ve not been able to find what the MCID was/is.

Both results were well below 2, even though the CIs barely reached it.

In both trials, ianalumab monthly led to a significantly greater decrease in the ESSDAI score at week 48 than placebo, with a between-group difference of −1.3 points (95% confidence interval [CI], −2.6 to 0.0; P=0.0496) in NEPTUNUS-1 and −1.0 points (95% CI, −2.0 to 0.0; P=0.04) in NEPTUNUS-2.

I can’t say it looks that promising if the outcomes are relevant and the MCIDs are reasonable.

 

[Jonathan Edwards]

I can’t say it looks that promising if the outcomes are relevant and the MCIDs are reasonable.

I suspect that for Sjögren's MCID is meaningless. Measuring benefit in these ANA-related diseases is a nightmare at best. Which is why it took 25 years for a trial to show that rituximab was useful in lupus. People do not design trials well because of bureaucracy. To my mind a statistically significant difference indicates that there is some effect. The tricky problem is deciding which people with Sjögren'smight get useful benefit. There was a time when I was confident that I had some skill with that sort of thing but most physicians have no idea of the biology and I am now too old to be in touch.

I suspect the drug reduces pathogenic antibody and I also suspect that for a select few people it could be of major value to their life quality. The licensing process and drug company philosophy is so far away from reality though.