In the global wave of CAR-T therapy expanding from oncology to autoimmune diseases, the question of who will be first to cross the finish line has been a focal point of industry attention.

 

On May 12, a key development in this race emerged: Kyverna Therapeutics has begun a rolling submission of its Biologics License Application (BLA) to the FDA for its CAR-T cell drug, mivocabtagene autoleucel (miv-cel, development code: KYV-101), for the treatment of stiff person syndrome (SPS).

 

This is not only the first BLA submission for an autoimmune CAR-T but also marks the first time, after years of competition, that someone has positioned themselves at the threshold of the finish line.

 

If miv-cel is successfully approved, it will not only open new growth avenues for Kyverna but also expand the commercial landscape of CAR-T therapy from oncology into the vast field of autoimmune diseases – a milestone for the entire cell therapy industry.

 

Kyverna's potential first-to-market is not an isolated narrative.

 

Behind it, a broader industrial transformation is rapidly taking shape: major players are placing substantial bets, in vivo and ex vivo technology routes are iterating, and Chinese players are emerging as a powerful force. These three forces are intersecting and resonating, propelling the autoimmune CAR-T field into an era of unprecedented high-speed development and intense competition.

 

TONACEA 01: Racing to Claim the Autoimmune CAR-T Space

 

Miv-cel is an autologous CD19 CAR-T cell therapy and one of the first autoimmune CAR-T products to enter clinical development. KYV-101 is currently being evaluated in various B-cell-mediated autoimmune diseases, with a focus on SPS, myasthenia gravis, and lupus nephritis.

 

The BLA submission for miv-cel is for SPS, a rare, progressive, and severely debilitating neuroautoimmune disease. Patients experience progressive muscle rigidity and painful spasms, with up to 80% eventually losing the ability to walk.

 

This rare disease affects only about 1–2 per million people. There are currently no FDA-approved therapies, and patients rely on off-label treatments with limited efficacy and significant side effects. Although the overall market size is not large, the SPS treatment space has far fewer competitors than other indications, and the rapidly progressive nature of the disease allows for faster clinical trial readouts.

 

Previously, Kyverna had concerns about whether the FDA would accept results from an open-label, uncontrolled study as sufficient evidence, especially after the agency rejected UniQure's plan to use an external control cohort to support its Huntington's gene therapy candidate.

 

However, in a recent meeting, the FDA agreed to Kyverna's plan, confirming that data from the single-arm KYSA-8 trial would be sufficient to support the SPS BLA submission.

 

According to data released by Kyverna in December 2025, among 26 patients, miv-cel met the primary endpoint, with a 46% improvement from baseline in the timed 25-foot walk test (T25FW) at week 16. 81% of patients achieved a "clinically meaningful" improvement, defined as at least a 20% reduction from baseline.

 

Detailed analysis presented in April at the AAN Annual Meeting also showed that among the 12 patients who required a walking aid at baseline, 8 (67%) no longer needed one at week 16. At the time of the last follow-up, all 26 patients in the KYSA-8 trial had discontinued all SPS-directed immunomodulatory or immunosuppressive treatments.

 

Secondary endpoints also showed significant improvements across multiple measures of disability, mobility, muscle stiffness, and spasm sensitivity.

 

Despite the breakthrough evidence, how long miv-cel's efficacy will last remains an open question – particularly important because CAR-T therapy typically requires only one infusion.

 

Dr. Amanda Piquet, the study's principal investigator at the University of Colorado, noted: "This requires continued observation, but early biomarker data already show evidence of this immune reset. Even just 16 weeks after treatment, the magnitude and consistency of the observed functional improvements are unprecedented."

 

Another positive indication that miv-cel's efficacy may be durable is that two SPS patients in Germany treated with miv-cel under compassionate use have achieved sustained efficacy for over 15 and 26 months, respectively, without requiring ongoing immunotherapy.

 

Kyverna has not yet completed all BLA submission materials. The company plans to release one-year follow-up data in the second half of 2026 to further validate long-term benefit.

 

On the commercial front, Kyverna states that its current manufacturing capacity can support the launch of miv-cel. In early May, the company appointed Nadia Dac as Chief Commercial Officer to lead commercialization preparations, with a planned product launch in 2027. Nadia Dac has nearly 30 years of marketing experience, having worked at AbbVie, Novartis, Pfizer, and other leading pharmaceutical companies, successfully launching multiple drugs and leading the launch of Yartemlea.

 

Beyond SPS, Kyverna continues patient enrollment for its Phase III trial for generalized myasthenia gravis (gMG). One-year long-term follow-up data from its Phase II trial have confirmed durable efficacy. Miv-cel has also shown positive preliminary data in an investigator-initiated trial (IIT) for progressive multiple sclerosis (PMS).

 

TONACEA 02: Global Clinical Race

 

While Kyverna is racing to complete its BLA submission, BMS's CAR-T candidate, zolacaptagene autoleucel (zola-cel), is carving out a differentiated competitive path in the treatment of scleroderma.

 

In January, clinicaltrials.gov registered the initiation of a Phase III trial for zola-cel in active systemic sclerosis (SSc).

 

This is a randomized, open-label, multicenter trial (n=92) designed to evaluate the efficacy and safety of zola-cel in combination with fludarabine and cyclophosphamide versus standard of care (tocilizumab, rituximab, nintedanib) in SSc. The primary endpoint is the absolute change from baseline in forced vital capacity (FVC) at month 12.

 

Zola-cel uses the same CD19 CAR construct as BMS's approved CAR-T product, Breyanzi, and is manufactured using the NEX-T platform, which aims to shorten manufacturing time (ex vivo manufacturing cycle of approximately 5 days), increase production efficiency, and improve CAR-T cell quality.

 

Zola-cel entered clinical development in 2020 and has completed Phase I validation in multiple autoimmune indications, including systemic lupus erythematosus (SLE), idiopathic inflammatory myositis, SSc, and multiple sclerosis, preliminarily validating its safety and potential efficacy across various autoimmune diseases.

 

Previously announced Phase I Breakfree-1 study results showed that in six patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD), a single infusion of zola-cel led to unprecedented improvements in lung function, with a median 10% increase from baseline in relative predicted FVC (pFVC) at six months.

 

For SSc-ILD patients, who have a very poor prognosis and limited effective treatment options, these results are highly significant and form the core confidence for BMS to accelerate this pipeline.

 

In April, when releasing its first-quarter 2026 results, BMS also updated its key milestone expectations, moving the readout date for registrational data for zola-cel from 2028 to 2027.

Another autoimmune CAR-T product that has entered Phase III is Descartes-08 from Cartesian Therapeutics.

 

Descartes-08 is a potential first-in-class (FIC) mRNA-engineered CAR-T cell therapy targeting BCMA to eliminate autoantibody-secreting plasma cells. Unlike traditional CAR-T, its administration does not require lymphodepleting chemotherapy, supports outpatient dosing, and avoids the risk of oncogenic genomic integration.

 

The Phase III AURORA trial for patients with myasthenia gravis continues to enroll. The trial plans to enroll 100 acetylcholine receptor autoantibody-positive (AChR Ab+) patients, with a dosing regimen of once-weekly outpatient infusions for six weeks. The primary endpoint is the proportion of patients with a ≥3-point improvement from baseline in the MG-ADL score.

 

Additionally, Descartes-08 will initiate the Phase II TRITON trial in myositis and continue the Phase I/II HELIOS pediatric trial in autoimmune diseases, including juvenile dermatomyositis.

Beyond these pipelines, the in vivo CAR-T wave over the past two years further underscores the high regard major players have for the autoimmune CAR-T field.

 

In June 2025, AbbVie acquired Capstan for US2.1 billion, betting on the potential of its core pipeline, CPTX2309, in autoimmune diseases. In October, BMS acquired Orbital for US2.1billion,bettingonthepotentialofitscorepipeline,CPTX2309,inautoimmunediseases.InOctober,BMSacquiredOrbitalforUS1.5 billion; Orbital's core product, OTX-201, was then at the IND filing stage for autoimmune disease treatment. In February, Eli Lilly entered the field with a US$2.4 billion acquisition of Orna, whose core pipeline is an in vivo CD19 CAR-T therapy for autoimmune diseases.

 

The core of treating autoimmune diseases lies in eliminating pathogenic B cells and re-establishing immune tolerance. In theory, in vivo CAR-T therapies could provide an efficient and safe solution for autoimmune diseases through transient or controllable CAR expression.

 

TONACEA 03: The Emerging Power of China

 

Substantial breakthroughs from Chinese players have also become an unignorable transformative variable in the development of autoimmune CAR-T.

In 2024, the number of clinical trials initiated in the CAR-T field in China historically surpassed that of the US, ranking first globally. Many Chinese biotech companies have responded rapidly to this new direction in autoimmune diseases, quickly laying out relevant pipelines.

 

In October 2025, IASO Biotherapeutics announced the online publication in Cell of its research results on the use of its proprietary, fully human BCMA-targeting CAR-T cell therapy, Equecabtagene Autoleucel, for the treatment of progressive multiple sclerosis (PMS).

 

The results showed that in five PMS patients, EDSS scores, nine-hole peg test performance, and 25-foot walk times significantly improved. Oligoclonal bands in cerebrospinal fluid disappeared completely, Kappa free light chain levels decreased significantly, and MRI follow-up detected no new or enlarged gadolinium-enhancing T1 lesions or T2 hyperintense lesions.

 

On safety, 80% of patients experienced only transient Grade 1 CRS, with no Grade ≥2 CRS. No immune effector cell-associated neurotoxicity syndrome (ICANS) or other neurotoxic reactions were observed.

 

Significantly, this study not only confirmed for the first time globally the safety and efficacy of CAR-T therapy for treating PMS but also marked the first time Cell published research results on the successful treatment of autoimmune diseases with a BCMA-targeted CAR-T cell therapy.

 

Around the same time, JW Therapeutics announced that it had submitted data from its Phase I study of relmacabtagene autoleucel (relma-cel) in Chinese adults with active SLE to the NMPA. Results showed that among 12 patients evaluable for six-month efficacy, 12 (100%) achieved SRI-4, 6 (50%) achieved LLDAS, and 12 (100%) achieved drug-free status.

 

In July 2025, Legend Biotech registered a Phase I clinical trial for LUCAR-G19 in autoimmune diseases on Clinicaltrials.gov. The study plans to enroll 42 patients with relapsed or refractory autoimmune diseases, covering indications including SLE, systemic sclerosis, ANCA-associated vasculitis, inflammatory myopathy, Takayasu arteritis, and IgG4-related disease, with primary completion expected in 2028.

 

In May, BRL Medicine, in collaboration with a team from Zhejiang University School of Medicine, published a paper in Cell Research, reporting for the first time globally the successful treatment of relapsed/refractory SLE using CRISPR/Cas9 gene-edited allogeneic anti-CD19 CAR-T cells (TyU19). The trial results showed that TyU19 could achieve rapid, deep clinical remission with an excellent safety profile, opening a new paradigm for treating autoimmune diseases.

 

In the in vivo CAR-T space, in September 2025, Hongxin Biotech published first-in-human clinical trial data in The New England Journal of Medicine (NEJM) for its mRNA-LNP-based in vivo CAR-T candidate, HN2301, in SLE patients. This study provided the first proof-of-concept for targeted LNP-based in vivo CAR-T therapy for SLE.

 

From BCMA to CD19, from autologous to universal, from ex vivo to in vivo, China's autoimmune CAR-T pipeline has formed a multi-dimensional, full-chain competitive landscape and is becoming a significant global force in this transformation.

 

TONACEA 04: The "Three Gates" of Commercial Realization

 

If the past decade has seen CAR-T therapy rewrite the history of cancer treatment, this transformation is now spreading with even greater ambition into the field of autoimmune diseases.

 

In 2021, a German team's first case of curing refractory SLE with CAR-T ignited industry enthusiasm for exploring autoimmune indications. After five years of development, with Kyverna now submitting the first BLA, autoimmune CAR-T stands on the eve of commercial realization.

 

But approval is never the finish line; it is the starting point of even greater challenges.

 

In February, a team led by Dr. Vinay Prasad, former Director of the FDA's Center for Biologics Evaluation and Research (CBER), published an article in the Annals of Internal Medicine acknowledging the potential of CAR-T therapies to offer durable, drug-free remission for patients with severe autoimmune diseases.

 

However, the article also cautioned about "unpredictable long-term toxicity." To address this, the FDA intends to work "case-by-case" with CAR-T developers, encouraging research in appropriate autoimmune populations and expressing a willingness to support the development of these novel cell therapies with flexible regulatory approaches.

 

This article highlights three core issues that the FDA will weigh carefully in its approval considerations:

 

First, the challenge of long-term safety: Autoimmune patients are generally younger and have longer life expectancies. Therefore, the FDA's tolerance for acute toxicities such as CRS and ICANS is far lower than for oncology drugs.

 

An even more critical concern is the risk of infection due to prolonged B cell/plasma cell depletion, as well as potentially delayed risks such as secondary malignancies and effects on fertility. Years of real-world data will be needed to demonstrate a favorable risk-benefit profile compared to lifelong immunosuppression. Companies must provide detailed long-term follow-up and risk management plans.

 

Second, the durability of efficacy and the definition of "cure": Although multiple cases of autoimmune patients achieving remission after CAR-T therapy have been reported, does this mean "cure"? The FDA needs solid evidence that such deep remission can persistently prevent organ damage caused by autoimmune diseases, not just provide short-term symptom control.

 

Furthermore, after "immune reset," can patients regain normal immune function, including the ability to respond to vaccines? If a patient remains disease-free but loses the ability to defend against infections, the long-term value of the therapy will be greatly diminished. The functional integrity of the reconstituted immune system is a question the FDA must answer when assessing the long-term benefit of autoimmune CAR-T.

 

Finally, the practical issue of cost and payment: This is the first real-world challenge following FDA approval. Cell therapies priced at several hundred thousand dollars, even if a single infusion might replace a patient's lifetime spending on immunosuppressants, present an upfront cost barrier that is daunting for both healthcare systems and individual patients.

 

How to transform these high-cost therapies into accessible treatment options through innovative payment models, risk-sharing agreements, or reimbursement negotiations, as well as through technology-driven cost reduction (e.g., universal CAR-T, in vivo CAR-T), is a problem the entire industry must work together to solve.

With the first autoimmune CAR-T on the horizon, a new chapter in cell therapy is about to begin.

 

But before celebrating the "miracle," the industry must clearly recognize: technological breakthrough is only the first step. Safety, durability, and accessibility are the three gates that must be crossed for this transformation to truly take hold.

 

References:

1. Kyverna, Kyverna Therapeutics Announces Initiation of Rolling SPS BLA Submission and Reports First Quarter 2026 Financial Results

2. FierceBiotech, Kyverna begins rolling submission for autoimmune CAR-T as FDA requests more natural history analysis

3. FierceBiotech, Racing toward first FDA nod for autoimmune CAR-T, Kyverna bolsters lead with full SPS dataset

4. TONACEA, The Comeback of the "First Autoimmune CAR-T Stock"

5. Drug Times, The Dawn Battle of Autoimmune CAR-T: Who Will Take the First Ticket?

6. TONACEA, The Battle of the Gods: BCMA CAR-T

7. TONACEA, In Vivo CAR-T: On the Eve of the Explosion

8. Pharma Innovation, FDA Officials Publish Article in Support, Accelerating Autoimmune CAR-T Development