Late-breaking Phase III data show ianalumab, Novartis’ dual-targeted antibody, reduced disease activity and patient burden in Sjögren’s disease, the pharma reported at the American College of Rheumatology Convergence congress on Wednesday.
It’s the second most common rheumatic autoimmune disease—and there is no targeted treatment available. Novartis aims to change that with ianalumab, presenting new data Wednesday showing reduced disease activity and patient burden in two Phase III trials in Sjögren’s disease, becoming the first drug to do so.
Ianalumab, pronounced yan-al-umab, is named after the Roman god Janus for its dual mechanism of action as a B cell depleting antibody that also targets the BAFF receptor. “The core premise was that this dual mechanism should allow us to more effectively deliver tissue level B cell depletion in difficult to treat autoimmune diseases,” Shreeram Aradhye, president of development and chief medical officer at Novartis, told BioSpace in an interview prior to the presentation.
That premise seemed to pay off, with ianalumab eliciting a greater reduction in disease activity by week 16 with improvements sustained through week 52 compared to placebo, as measured by the EULAR Sjögren’s Syndrome Disease Activity Index, meeting the studies’ primary objective. In addition, patients treated with ianalumab also saw consistent improvements in dryness, pain and fatigue—all hallmark symptoms of Sjögren’s.
The data, from the Phase III NEPTUNUS-1 and NEPTUNUS-2 trials, were presented at the American College of Rheumatology Convergence congress in Chicago on Wednesday. Novartis first announced topline results from NEPTUNUS-1 and NEPTUNUS-2 in August.
Aradhye characterized Sjögren’s as a “difficult, heterogeneous disorder,” with varied manifestations. Sjögren’s is estimated to afflict between 3 million and 4 million people in the U.S., around 90% of whom are women, according to Sjogren’s Advocate.
Current options for Sjögren’s are only symptomatic treatments, with patients turning to eye drops and unapproved immunomodulators, Aradhye said. The general theme that has emerged, based on discussions with rheumatologists and patient representatives, is that if a targeted drug is approved with “a profile that is reasonably safe . . . there is the expectation that people will want to try it,” he added.
Novartis plans to submit the Phase III results to global regulators early next year.
“It’s an exciting time for our immunology portfolio,” Aradhye said, highlighting both the ianalumab data in Sjögren’s and a successful Phase III readout last week for Cosentyx, first approved in 2015 to treat plaque psoriasis, in people over 50 with polymyalgia rheumatica.
Besides Sjögren’s, which is listed on Novartis’ pipeline page as the lead indication for ianalumab, the drug is also in Phase III trials for systemic lupus erythematosus (SLE) and lupus nephritis, in Phase II for systemic sclerosis, and in earlier-stage development for three hematological indications. Aradhye expects the lupus trials to read out in the 2027 timeframe.
He explained Novartis’ drug development philosophy. “We’ve had this common theme around saying that when we understand a drug and its mechanism of action, we will evaluate it in multiple indications simultaneously.”
Immunology is one of four key therapeutic areas at Novartis, the others being cardiovascular, renal and metabolic, neuroscience and oncology.
Novartis has had a “long legacy” in immunology, Aradhye said, pointing to the company’s work in transplantation and with Cosentyx. In this space, Novartis is committed to another emerging theme: the use of CAR T in autoimmune diseases—something that has been front and center at ACR this week. This is somewhat of a natural fit for Novartis, given its ownership of Kymriah, a CD-19 directed CAR T that in 2017 became the first cell-based gene therapy approved by the FDA, to treat acute lymphoblastic leukemia.
Novartis will also present biomarker data at ACR from a Phase I/II study of its autologous CD-19 CAR T therapy, rapcabtagene autoleucel (YTB323), in SLE.
YTB323 has previously shown “good proliferation of the clones, a decrease in B cells, reconstitution over time and then a meaningful control of disease activity” in lupus and lupus nephritis, Aradhye said.
Novartis has dominated the biopharma headlines this past week, announcing its intent on Sunday to acquire neuromuscular drug developer Avidity Biosciences for around $12 billion—the year’s second largest deal—and reporting Q3 earnings on Tuesday. Novartis also announced on Tuesday the successful completion of its $1.4 billion purchase of Tourmaline Bio.
