Efficacy and Safety of Ianalumab in Sjogren's Disease Save
Drs. Yuz Yusof and Xavier Mariette discuss abstract OP0126 presented at the 2026 EULAR meeting in London
Transcription
Hello everyone. My name is Dr. Yse Yusuf. I'm from Leeds, United Kingdom. I'm reporting for RheumNow to cover the EULAR 2026 Congress in London, United Kingdom. Today is the first day of the congress, and there have been many abstracts that were presented, and the majority of them are very, very good studies.
So the one that caught my eye was presented in the Sjögren's abstract session. The session itself is really interesting — it's called "Positive Clinical Trials in Sjögren's." So it's a really exciting time for Sjögren's disease, and today I'm delighted to be joined by the presenting author, Professor Xavier Mariette. Hello, Xavier. Hello. Hello, Yse. Hello. Yeah, thank you for joining us.
Today we will be discussing the abstract titled OP0126. So basically this is about the efficacy and safety of ianalumab for the treatment of Sjögren's disease, and the results are up to 108 weeks.
So Xavier, can you please enlighten us about the background of the study and design? Yes, thank you. So the background of this study is that B cell activity and BAFF are key elements in the pathogenesis of Sjögren's disease. You do know that B cells play a key role, and my group has demonstrated now 23 years ago that the BAFF cytokine was elevated in this disease and correlated with the level of autoantibodies, and the BAFF cytokine is a key element for activating the B cells.
So ianalumab is a monoclonal antibody that targets the BAFF receptor, and in doing that it has a dual action. The first one is to deplete the B cells, because the BAFF receptor is expressed at the surface of the B cells. And we do know that after B cell depletion there is an increase in BAFF in the serum, and this increase in BAFF may reactivate new autoimmune B cells. But with ianalumab, which blocks the receptor, this increase in BAFF will not result in activity of autoimmune B cells. So that is the dual action of the drug.
Yeah. Thank you. And just please summarize a little bit of the study design of these NEPTUNE trials. Yeah. So the NEPTUNE trial is the first positive phase three in Sjögren's disease. So it's a big step in the treatment of the disease. So actually there are two concurrent randomized phase three studies — NEPTUNE 1 and NEPTUNE 2 — and each of the studies achieved its primary endpoint, which is the decrease of ESSDAI from baseline, and that was presented at ACR as a late-breaking abstract.
So the primary endpoint — and for this study at the EULAR presentation — you also present the data up to week 108. Can you please tell us more about the efficacy of the treatment up to week 108 briefly? Yes. So the NEPTUNE study concerns patients with systemic activity — it means patients with ESSDAI of five or more. And so as I said, the primary endpoint was achieved, and in this presentation I gave new data.
The first one is the evolution of different domains of ESSDAI, because ESSDAI is a composite score with 12 domains, and actually we found that 60% of the improvement is observed thanks to clinical domains and 40% of the improvement refers to the biological domain. So that is the first new result.
The second new result is that the Sjögren's community is setting up a new composite outcome which is called STAR. And in the NEPTUNE study there was a significant improvement of STAR in patients treated with ianalumab compared with placebo, with an effect size of 15 to 20%.
And the third new data concern the evolution of biomarkers that are linked to the risk of developing lymphoma, which is one of the main risks of the disease. And actually we found that rheumatoid factor was decreased — and rheumatoid factor is an increased risk of lymphoma. C4 was increased, because low C4 is an increased risk of lymphoma. And we also demonstrated that the BAFF receptors were completely occupied by the doses of ianalumab, meaning that BAFF cannot act anymore, and we do know that BAFF is a risk factor of lymphoma in the disease.
Brilliant. Fantastic. So that's based on the clinical and immunological activity. So how about patient-reported outcomes? Do you see any signal of improvement there? Yeah. When we pool the two studies of NEPTUNE 1 and NEPTUNE 2, we see a significant difference comparing to placebo regarding the patient global assessment and the physician global assessment. The other PRO — for example, the ESSPRI score — was not statistically different between the two groups, but there is a trend. So there are also some signals suggesting there is also an improvement in patient burden.
Okay. So in terms of safety up to week 108, was there anything that we need to be looking out for? Yeah. And it is a further result I have presented regarding the extension use. So after 52 weeks, the patients treated with ianalumab continue to be treated, and the patients treated on
placebo are randomized between ianilimab QM and Q3M. [clears throat] And if you compare the evolution of these two groups, firstly the patients who continue ianilimab QM [clears throat] continue to improve SDI, and the patients on placebo the curve is going to go just with the other patients. So you have a reduction of SDI in these patients. So it confirmed the efficacy, and regarding safety there was no signal in the randomized phase of the study between placebo and ianilimab, and when continued up to two years it is the same, and especially there is no increased risk of infection in the patients treated with the drug for two years.
I mean, this all being said, one last question. So now that this compound shows promising phase three results, I'm just wondering whether — do you know how long we would expect in terms of regulatory approval and when can we then start fitting it into our clinical pathways?
That's a $1,000 question, and it will depend on the agencies. I do know that Novartis, which is the sponsor of the study, requested fast access to the market from the FDA. What I know is that they are in the process of discussion with the two agencies, FDA and EMA, in order to have probably a fast approval, and it could be around during the year 2027. And it is a hope for the patients, but again it concerns the patients with systemic complications, and today we don't know yet if the drug will also be efficient in the patients with fatigue, dryness, and pain but without systemic complications. So it is planned to do a specific study in this kind of patients to see if the drug also works in this subset of patients.
Absolutely. Yeah. Thank you so much. And like I say, thank you so much for your explanation. And it's really great news for the field of Sjögren's, and certainly for both clinicians and also for our patients. So thank you so much for your time to be interviewed today. Thank you everyone for listening. Follow RheumNow for more content and coverage. Thank you. Bye-bye. Okay, thank you.
So the one that caught my eye was presented in the Sjögren's abstract session. The session itself is really interesting — it's called "Positive Clinical Trials in Sjögren's." So it's a really exciting time for Sjögren's disease, and today I'm delighted to be joined by the presenting author, Professor Xavier Mariette. Hello, Xavier. Hello. Hello, Yse. Hello. Yeah, thank you for joining us.
Today we will be discussing the abstract titled OP0126. So basically this is about the efficacy and safety of ianalumab for the treatment of Sjögren's disease, and the results are up to 108 weeks.
So Xavier, can you please enlighten us about the background of the study and design? Yes, thank you. So the background of this study is that B cell activity and BAFF are key elements in the pathogenesis of Sjögren's disease. You do know that B cells play a key role, and my group has demonstrated now 23 years ago that the BAFF cytokine was elevated in this disease and correlated with the level of autoantibodies, and the BAFF cytokine is a key element for activating the B cells.
So ianalumab is a monoclonal antibody that targets the BAFF receptor, and in doing that it has a dual action. The first one is to deplete the B cells, because the BAFF receptor is expressed at the surface of the B cells. And we do know that after B cell depletion there is an increase in BAFF in the serum, and this increase in BAFF may reactivate new autoimmune B cells. But with ianalumab, which blocks the receptor, this increase in BAFF will not result in activity of autoimmune B cells. So that is the dual action of the drug.
Yeah. Thank you. And just please summarize a little bit of the study design of these NEPTUNE trials. Yeah. So the NEPTUNE trial is the first positive phase three in Sjögren's disease. So it's a big step in the treatment of the disease. So actually there are two concurrent randomized phase three studies — NEPTUNE 1 and NEPTUNE 2 — and each of the studies achieved its primary endpoint, which is the decrease of ESSDAI from baseline, and that was presented at ACR as a late-breaking abstract.
So the primary endpoint — and for this study at the EULAR presentation — you also present the data up to week 108. Can you please tell us more about the efficacy of the treatment up to week 108 briefly? Yes. So the NEPTUNE study concerns patients with systemic activity — it means patients with ESSDAI of five or more. And so as I said, the primary endpoint was achieved, and in this presentation I gave new data.
The first one is the evolution of different domains of ESSDAI, because ESSDAI is a composite score with 12 domains, and actually we found that 60% of the improvement is observed thanks to clinical domains and 40% of the improvement refers to the biological domain. So that is the first new result.
The second new result is that the Sjögren's community is setting up a new composite outcome which is called STAR. And in the NEPTUNE study there was a significant improvement of STAR in patients treated with ianalumab compared with placebo, with an effect size of 15 to 20%.
And the third new data concern the evolution of biomarkers that are linked to the risk of developing lymphoma, which is one of the main risks of the disease. And actually we found that rheumatoid factor was decreased — and rheumatoid factor is an increased risk of lymphoma. C4 was increased, because low C4 is an increased risk of lymphoma. And we also demonstrated that the BAFF receptors were completely occupied by the doses of ianalumab, meaning that BAFF cannot act anymore, and we do know that BAFF is a risk factor of lymphoma in the disease.
Brilliant. Fantastic. So that's based on the clinical and immunological activity. So how about patient-reported outcomes? Do you see any signal of improvement there? Yeah. When we pool the two studies of NEPTUNE 1 and NEPTUNE 2, we see a significant difference comparing to placebo regarding the patient global assessment and the physician global assessment. The other PRO — for example, the ESSPRI score — was not statistically different between the two groups, but there is a trend. So there are also some signals suggesting there is also an improvement in patient burden.
Okay. So in terms of safety up to week 108, was there anything that we need to be looking out for? Yeah. And it is a further result I have presented regarding the extension use. So after 52 weeks, the patients treated with ianalumab continue to be treated, and the patients treated on
placebo are randomized between ianilimab QM and Q3M. [clears throat] And if you compare the evolution of these two groups, firstly the patients who continue ianilimab QM [clears throat] continue to improve SDI, and the patients on placebo the curve is going to go just with the other patients. So you have a reduction of SDI in these patients. So it confirmed the efficacy, and regarding safety there was no signal in the randomized phase of the study between placebo and ianilimab, and when continued up to two years it is the same, and especially there is no increased risk of infection in the patients treated with the drug for two years.
I mean, this all being said, one last question. So now that this compound shows promising phase three results, I'm just wondering whether — do you know how long we would expect in terms of regulatory approval and when can we then start fitting it into our clinical pathways?
That's a $1,000 question, and it will depend on the agencies. I do know that Novartis, which is the sponsor of the study, requested fast access to the market from the FDA. What I know is that they are in the process of discussion with the two agencies, FDA and EMA, in order to have probably a fast approval, and it could be around during the year 2027. And it is a hope for the patients, but again it concerns the patients with systemic complications, and today we don't know yet if the drug will also be efficient in the patients with fatigue, dryness, and pain but without systemic complications. So it is planned to do a specific study in this kind of patients to see if the drug also works in this subset of patients.
Absolutely. Yeah. Thank you so much. And like I say, thank you so much for your explanation. And it's really great news for the field of Sjögren's, and certainly for both clinicians and also for our patients. So thank you so much for your time to be interviewed today. Thank you everyone for listening. Follow RheumNow for more content and coverage. Thank you. Bye-bye. Okay, thank you.
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