Novartis recently announced that it had released positive results from two late-stage trials using ianalumab for the treatment of patients with Sjögren’s disease, dubbed NEPTUNUS-1 and NEPTUNUS-2. The point was to see if this drug would be able to achieve the primary endpoint of the EULAR Sjögren’s Syndrome Disease Activity Index [ESSDAI] score. It was noted by this big pharma that this intended efficacy primary endpoint was met in a statistically significant manner. This particular disorder is harsh, and what it entails is the immune system attacking the glands responsible for controlling moisture of a person’s body. What are typically affected by this disease are the eyes and mouth as part of the salivary system.
With that being said, the company wanted to expand its horizons here and not just focus on this specific subset of Sjögren’s disease patients. In essence, the study was put into motion to go after patients with extraglandular disease. What this means is other organs that are affected with moisture dysfunction beyond that of the eyes and mouth. With that being said, the ESSDAI score is put in place to measure disease severity, with 123 total points being possible. The higher the score, the higher the disease symptom severity in place as part of the 12 domains being looked at with this scoring system. On the flip side, a lower score indicates less disease severity.
This is a huge win for patients with this autoimmune disorder, specifically because it could provide them with the first-ever disease-modifying drug for them. It is expected that detailed data from these late-stage studies will be shown at an upcoming medical conference. Thus, there will be more light shed on how the primary endpoint was met and likely other positive findings to be noted at the very same time. More important than this is that Novartis has enough data on hand to submit regulatory applications to health authorities around the globe. There is no doubt that this is an unmet medical need, as current therapies available to these patients don’t target the underlying systemic cause of disease.
Instead, patients are treated for their symptoms. In the case of dry eyes and dry mouth, patients are given artificial tears and saliva production therapies. When there is organ involvement, which is far more severe, corticosteroids are given alongside rituximab, cyclophosphamide, or other immunosuppressants. As you can see, treatment options for these patients are limited. The science of ianalumab involves a dual mode of action. You have antibody-dependent cellular cytotoxicity [ADCC] to deplete B-cells, causing disease, and then the blocking of the BAFF-R pathway, which is needed for B-cell survival. There is far more that can be done with this monoclonal antibody after this company has achieved this win in treating these Sjögren’s disease patients.
There is ongoing development to use this drug to target other B-cell-mediated autoimmune disorders, which brings about a host of expansion opportunities. It is being investigated for targeting other autoimmune disorders like immune thrombocytopenia and systemic lupus erythematosus [SLE], plus many others. This wasn’t a drug that it had developed on its own; instead, it was first being developed in collaboration with MorphoSys AG, and later on, it had acquired it in 2024, which brought this monoclonal antibody into its pipeline. Novartis didn’t always have luck in targeting Sjögren’s disease; it had a major setback when another drug iscalimab, an anti-CD40 antibody developed by the company itself, didn’t have a good risk/benefit profile in place.
The drug was shown to have done well with the ESSDAI score noted above in terms of efficacy, but not so well in terms of safety. Especially with an event of a fatal infection in one patient. With this in mind, Novartis made the decision to discontinue this drug for further development of this autoimmune disorder. As is evidenced by today’s win with ianalumab, all is not lost, as the company can still move forward in bringing a therapy that could potentially treat the underlying systemic cause of disease. That is, if approved by regulators, this could end up being the first targeted treatment for them. The strong efficacy of this BAFF-R [B-cell activating factor receptor] inhibitor isn’t the only win; the drug was shown to be safe and tolerable. This overcomes the prior obstacle of the risk/benefit profile it had with iscalimab.
Novartis is set to present these results of the NEPTUNUS-1 and NEPTUNUS-2 studies at an upcoming medical conference, and the hope is that investors are impressed with the clinical data released. Beyond that, the company is continuing on with testing of ianalumab, in that patients were given two options, which were to continue to be followed for an extended period of time or to be entered into a long-term extension study. I believe the importance of this will be to see if this therapy provides a long-term impact on patients’ lives going forward.