Table 7.

Comparison of Frexalimab with other current, investigational, and gold-standard treatments for various autoimmune diseases

Condition	Therapy	Comparison with frexalimab
Multiple sclerosis (MS)	DMTs 1. Natalizumab (Tysabri) 2. Ocrelizumab (Ocrevus)	1. Natalizumab (Tysabri) MOA: Monoclonal antibody targeting α4-integrin to prevent leukocyte migration into the CNS Efficacy: Highly effective in reducing relapse rates and slowing progression in relapsing MS. Demonstrated significant reduction in relapse rates and MRI lesion activity. Sixty-eight percent reduction compared to placebo. Limited data is available on frexalimab specifically for MS. Safety: Risk of PML (Progressive Multifocal Leukoencephalopathy), infections, and liver enzyme abnormalities. Frexalimab has immune-related adverse events (e.g. pneumonitis, colitis). The safety profile is still under investigation. Overall: Well-established gold standard for relapsing MS with proven efficacy and a known risk profile; requires monitoring for PML. While on frexalimab ongoing trials will be crucial to determine its role in MS treatment. Potential for novel dosing and monitoring protocols based on immune modulation effects. 2. Ocrelizumab (Ocrevus) MOA: Monoclonal antibody targeting CD20+ B cells to deplete autoreactive B cells Efficacy: Highly effective in reducing relapse rates and slowing progression in both relapsing and primary progressive MS while Frexalimab showed 71–84% reduction vs placebo in ARR Safety: Infusion-related reactions, increased risk of infections, potential malignancies; generally well-tolerated Frexalimab: Available from pivotal trials; ongoing long-term studies Overall: Established gold standard for both relapsing and primary progressive MS; effective with a generally manageable safety profile
2. Sjögren’s syndrome	1, Hydroxychloroquine (Plaquenil) 2, Secukinumab (Cosentyx)	1, Hydroxychloroquine (Plaquenil) MOA: Antimalarial drug with immunomodulatory effects; reduces inflammation and autoimmunity Efficacy: -Widely used as part of standard treatment. Effective in reducing disease activity and improving symptoms in some patients. Safety: -Generally well-tolerated. - Side effects include gastrointestinal disturbances, retinal toxicity (rare), and skin rashes. Overall - Hydroxychloroquine is a gold standard for managing symptoms in Sjögren’s Syndrome with a well-established efficacy profile. - Generally well-tolerated and effective for many patients. Frexalimab could potentially offer a novel treatment for Sjögren’s Syndrome through its unique mechanism of targeting PD-1/PD-L1.However, Clinical trials and data are needed to establish its efficacy and safety specifically for Sjögren’s Syndrome. Promising as an investigational therapy Secukinumab (Cosentyx) MOA: Monoclonal antibody targeting IL-17A to reduce inflammation and immune response Efficacy: -Investigational for Sjögren’s Syndrome. Early studies showed potential in reducing disease activity and symptoms but not yet standard treatment. Safety: -Investigational safety profile. Possible side effects include infections, injection site reactions, and effects on the immune system. overall Secukinumab is an investigational therapy with promising early data
Type 1 diabetes SLE	1.Insulin therapy (Gold Standard) 2. Teplizumab (Tzield) 1.Hydroxychloroquine (Plaquenil) 2. Belimumab (Benlysta)	1. Insulin therapy (Gold Standard) Not directly disease-modifying; provides external insulin to regulate blood glucose levels while for Frexalimab early-phase data is needed for Type 1 Diabetes. Efficacy: Does not modify the underlying disease but is critical for managing symptoms and preventing complication While Frexalimab has the ability to modulate immune response and restore β-cell function. Safety: -Well-established safety profile. - Risks include hypoglycemia, insulin allergic reactions, and weight gain. - Requires careful management to avoid complications. While in case of Frexalimab safety profile is under investigation. Also, there is also potential for immune-related adverse events such as pneumonitis, colitis, and endocrinopathies. However, for specific safety data for Type 1 Diabetes is not yet established Overall - Insulin Therapy is the gold standard for managing Type 1 Diabetes. Frexalimab has potential to modulate immune response and preserve β-cell function, which could modify disease progression unlike insulin therapy. 2. Teplizumab (Tzield) Moa: Monoclonal antibody targeting CD3 to modulate immune response and preserve pancreatic β-cell function Efficacy: -Demonstrated efficacy in delaying the onset of insulin dependence in recent studies. - Shows potential in preserving β-cell function in newly diagnosed patients. Safety: Safety profile includes risks of infections, infusion reactions, and potential effects on the immune system. – Generally well-tolerated in clinical trials but needs further monitoring. Overall Teplizumab is an investigational therapy with promising results in delaying the progression of Type 1 Diabetes. It is a potential disease-modifying treatment. Not yet widely available but shows potential for preserving β-cell function in newly diagnosed patients. 1.Hydroxychloroquine (Plaquenil) Moa: Modulates immune response and reduces inflammation; interferes with antigen processing and immune cell activity Efficacy: -Well-established for managing SLE symptoms. It has been shown to reduce the risk of disease flares, decrease steroid dosage, prevent organ damage, and reduce thrombotic effects. In the case of Frexalimab, early data suggest it may improve disease outcomes by targeting specific immune pathways. However, the results are not yet fully established. Safety: Generally well-tolerated. - Side effects include gastrointestinal disturbances, retinal toxicity (rare), and skin rashes. For Frexalimab, the safety profile is under investigation. Specific safety data for SLE is not yet established. Overall: Hydroxychloroquine is a gold standard for managing SLE symptoms. 2. Belimumab (Benlysta) moa: Monoclonal antibody targeting B-lymphocyte stimulator (BLyS) to reduce B-cell activity and autoantibody production Efficacy: helps in reducing disease activity and flares in SLE. Proven to improve outcomes in clinical trials for moderate to severe SLE. Safety: Potential side effects include infusion reactions, infections, and potential impact on immune function. Generally well-tolerated in clinical trials but requires monitoring Overall Belimumab is an effective treatment for moderate to severe SLE, targeting a specific component of the immune system. Frexalimab could provide a new method for modulating immune response, complementing or offering an alternative to targeting BLyS