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iStock/ JHVEPhoto 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 pro 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. Cell therapy 5 CAR T Cell Therapies With Autoimmune Readouts in 2025 Having established success in cancer, biopharma is now looking to leverage CAR T therapies against a new target, autoimmune disorders, with several early- to mid-stage readouts expected this year. March 17, 2025 · 9 min read · Tristan Manalac 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.

iStock, wildpixel The patient-specific nature of autologous cell therapies presents unique challenges that can best be addressed by a middle path between on-site and centralized manufacturing. Since the 2017 approval of Novartis’ Kymriah for a form of leukemia demonstrated the feasibility and transformative potential of CAR T cell therapies for cancer, the field has experienced a wave of investment and innovation, leading to multiple marketed products. However, it’s increasingly clear that current approaches to manufacturing are not conducive to achieving consistent, sustainable and globally accessible manufacturing of high-quality cell therapies. Producing an autologous cell therapy is a lengthy, highly technical and demanding manual process, from cell collection and shipping from an individual hospital to modification in a manufacturer’s facility, to return shipping and administration of the final product. As a result, costs are high and access is limited. As more cell therapies enter the scene, the existing system will experience significant strain. I’ve spent the past 15 years of my career working in chemistry, manufacturing and controls (CMC) and regulatory affairs for novel biologics, first-to-market monoclonal antibodies (mAbs), and now in cell-based therapies. While uniform starting materials, robust and scalable processes and powerful analytics supported large-scale, centralized manufacturing of mAbs, autologous cellular therapies require a unique approach. That’s because patients are part of the supply chain, as the starting material comes from their own cells or tumor; therefore, patient proximity is a key factor. Moreover, given that many of these patients have rapidly progressing disease, this process creates a race against time to produce and return a therapeutic product while they are still eligible for treatment. In my role at CTMC (the Cell Therapy Manufacturing Center), launched by the University of Texas MD Anderson Cancer Center and National Resilience in 2022, I’ve seen how many innovative therapies in the field fail to reach their full potential. To build a strong foundation for the long-term success and scalability of cell therapies, we need a reimagined manufacturing system designed to accommodate future growth and ensure accessibility. In my view, a regionalized manufacturing model is the best approach. Decentralization’s Pain Points Given the highly technical manufacturing process of cell therapies, even well-equipped hospitals are overwhelmed with the logistics of preparing and shipping patient material. This complexity also limits the global accessibility of cellular therapies, as the shipping time and customs requirements associated with receiving starting material from abroad—not to mention the evolving regulations governing such shipments—can be prohibitive. While a fully decentralized manufacturing model, with each hospital producing the cell therapies it administers, may be an attractive prospect, it poses greater challenges than the current system for scalable, reproducible production of high-quality cellular therapies given regulators’ high expectations for establishing comparability across sites. Even if comparability can be demonstrated, changes in operators, supply chain disruptions and other factors can lead to a gradual drift in processes over time. Without a fully digitized infrastructure, a highly experienced staff and proximity to the supply chain, these issues cannot be uniformly addressed. The Regional Solution Rather than fully centralized or decentralized manufacturing, then, the most feasible approach lies between these two options. By investing time and resources into building high-capacity, state-of-the-art facilities, we can achieve greater scalability, consistency and quality than would be possible with numerous smaller, manual sites. A regionalized manufacturing model involves multiple manufacturing hubs that serve as cell therapy “pharmacies” for the surrounding area. Rather than coordinating and navigating the logistics of each individual drugmaker’s shipping process, area hospitals could work with a single regional manufacturing hub equipped to produce multiple sponsors’ products. This system streamlines hospital processes, reduces turnaround times for patients, and overcomes communication and logistical barriers to global access. Although a regionalized model does not eliminate the challenge of establishing comparability, strategic planning and technological innovations can help expand control over both the process and product. Infrastructure investments such as process automation, for example, can overcome variability associated with manual processing and ensure consistent manufacturing methods that can be replicated across sites. Powerful, advanced analytics can provide in-depth data insights and identify critical quality attributes to demonstrate site-to-site comparability of products. Additionally, strategies like using split starting material in comparability studies to overcome issues of donor variability can further strengthen submission data. Importantly, site-to-site comparability should be addressed proactively, not as an afterthought. Early engagement with the FDA allows organizations to align with regulators on comparability study design and minimize unexpected pitfalls when it is time to scale. In such a new industry, regulators and drugmakers alike are continuously learning and adapting to evolving technologies. Ori Biotech, for example, recently received Advanced Manufacturing Technology (AMT) designation from the FDA. This designation recognizes novel manufacturing technologies that have the potential to substantially improve manufacturing processes and provides sponsors utilizing AMTs with enhanced regulatory engagement to accelerate product development and commercialization. CTMC is part of Ori’s preferred partner network, and data produced through our collaboration contributed to Ori’s achievement of this designation. This experience reinforces how building strong relationships with regulators—and approaching regulatory interactions as a collaborative process—can pave the way for long-term success in the development and commercialization of cell-based products. As the field of cell therapy continues to expand and progress, current manufacturing models will be insufficient to deliver the full potential of these groundbreaking therapies. The approaches that fueled the first decade of cellular therapies cannot sustain the field in the future. Making safe, high-quality autologous cellular therapies more cost-effective and globally accessible will require a manufacturing approach as unique as the treatments themselves. In this way we can fully realize their transformative potential.