FDA Clears IND for CAR-T Cell Therapy Equecabtagene Autoleucel in Multiple Sclerosis

Yongke Zhang, MD, PhD

(Credit: IASO Bio)

According to a new announcement, the FDA has cleared IASO Biotechnology’s investigational new drug application (IND) to test equecabtagene autoleucel in patients with multiple sclerosis (MS). Equecabtagene autoleucel, an autologous anti-B cell maturation antigen (BCMA)-directed chimeric antigen (CAR)-T cell therapy, is also in development for other autoimmune conditions, including myasthenia gravis (MG), neuromyelitis optica spectrum disorder (NMOSD), and multiple myeloma.¹

The company did not release any details as to the next steps of its clinical development, or when it may begin clinical trials involving patients with MS. This was the second FDA IND approval of equecabtagene autoleucel for the treatment of autoimmune diseases in 2024, following refractory MG in early April.

"In an investigator initiated trial (IIT) conducted in China, Eque-cel has shown promising efficacy in 6 autoimmune diseases. The IND approval of Eque-cel in the treatment of MS from the FDA is another strong evidence of IASO Bio's ongoing dedication and technological advancements in the treatment of autoimmune diseases," Yongke Zhang, MD, PhD, chief scientific officer at IASO Bio, said in a statement.¹ "We will continue to adhere to the research and development philosophy that prioritizes clinical value to address unmet clinical needs and will place great importance on implementing a global strategy. Through close collaboration and in-depth exchanges with international clinical research institutions, we aim to accelerate the development and commercialization of more innovative drugs, bringing greater benefits to patients worldwide."

Equecabtagene autoleucel was previously assessed in an investigator-initiated, open-label, single-arm, phase 1 trial of patients with NMOSD, which was published in Signal Transduction and Targeted Therapy in 2023. The trial featured 12 participants with a median age of 49.5 years who were treated with equecabtagene autoleucel, otherwise known as CT103A. All told, the therapy showed a manageable safety profile, with hematologic toxic effects as the only common events of grade 3 or higher.²

READ MORE: Spinal Movement Disorders Prevalent in Non-MS Demyelinating Disorders of Spinal Cord

During the follow-up of a median 5.5 months, 11 patients had no relapse; all patients generally reported improvement in disabilities and quality-of-life outcomes; and 11 patients with aquaporin-4 antibodies in serum showed a downward trend by the cutoff date. CAR T-cell therapy expansion was associated with responses and persisted more than 6 months post-infusion in 17% of the patients. In the study, 7 patients (58%) developed infections, but no grade 4 infections occurred.

The therapy was also assessed in a small-scale, investigator-initiated, open-label study of 2 individuals with refractor MG. One was a 33-year-old female, AChR-IgG and Titin-IgG positive, who had been treated with thymectomy 21 months prior to enrollment and had not achieved clinical remission after treatment with cholinesterase inhibitors, glucocorticoids, immunosuppressants, and anti-CD20 monoclonal antibody. The other subject was a 60-year-old female, MuSK-IgG4 positive, with a 20-year history of the disease and failed previous treatment with hormones, immunosuppressants, and anti-CD20 monoclonal antibody.³

After being treated with a single infusion of equecabtagene autoleucel at the dose of 1.0 x 106, clinical symptoms continued to improve over an 18-month period. From 3 months after the infusion, patients showed significant improvement in limb strength and vital capacity and sustained improvement in Myasthenia Gravis Activities of Daily Living Score, Quantitative Myasthenia Gravis Score, Myasthenia Gravis-Quality of Life Score, and Modified Rankin score. Of the 2 individuals, only 1 participant developed grade 1 cytokine release syndrome, and no immune effector cell-associated neurotoxicity syndrome. Overall, the therapy’s safety profile was superior compared with that of the multiple myeloma indication.

REFENCES
1. IASO Bio Receives U.S. FDA Approval of Investigational New Drug Application for Equecabtagene Autoleucel for Multiple Sclerosis. News release. IASO Bio. July 23, 2024. Accessed July 24, 2024. https://www.prnewswire.com/news-releases/iaso-bio-receives-us-fda-approval-of-investigational-new-drug-application-for-equecabtagene-autoleucel-for-multiple-sclerosis-302204711.html
2. Qin C, Tian D, Zhou L, et al. Anti-BCMA CAR T-cell therapy CT103A in relapsed or refractory AQP4-IgG seropositive neuromyelitis optica spectrum disorders: phase 1 trial interim results. Signal Transduction and Targeted Therapy. 2023;8:5. doi:10.1038/s41392-022-01278-3
3. IASO Bio Announces U.S. FDA Approval of Investigational New Drug Application for BCMA CAR-T Equecabtagene Autoleucel for Generalized Myasthenia Gravis. News release. IASO Bio. April 4, 2024. Accessed July 24, 2024. https://www.prnewswire.com/news-releases/iaso-bio-announces-us-fda-approval-of-investigational-new-drug--application-for-bcma-car-t-equecabtagene-autoleucel-for-generalized-myasthenia-gravis-302108912.htmhttps://www.prnewswire.com/news-releases/iaso-bio-announces-us-fda-approval-of-investigational-new-drug--application-for-bcma-car-t-equecabtagene-autoleucel-for-generalized-myasthenia-gravis-302108912.htm