Rituximab biosimilars

Chimeric mouse-human IgG1 kappa monoclonal antibody of about 145 kDa, with murine variable regions and human constant regions, produced in Chinese hamster ovary cells. It was the first monoclonal antibody approved for cancer.

Binds the CD20 antigen on the surface of pre-B and mature B lymphocytes and depletes them through complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity and direct induction of apoptosis. All three routes depend on the Fc region, so Fc glycosylation and effector potency are the critical quality attributes in biosimilar comparisons.

Intravenous infusion; half-life about 22 days in lymphoma patients at the 375 mg per m2 dose, longer in rheumatoid arthritis, with clearance falling as tumour burden and circulating B cells are depleted. A subcutaneous formulation with hyaluronidase exists for the reference product in some markets.

Lymphoma: 375 mg per m2 per cycle with chemotherapy, or as maintenance every two or three months. Chronic lymphocytic leukaemia: 375 then 500 mg per m2. Rheumatoid arthritis: two 1,000 mg infusions two weeks apart. Supplied as 100 mg/10 mL and 500 mg/50 mL concentrate for infusion at 10 mg/mL.

• Non-Hodgkin lymphoma: follicular lymphoma and diffuse large B-cell lymphoma
• Chronic lymphocytic leukaemia
• Rheumatoid arthritis after inadequate response to TNF inhibitors
• Granulomatosis with polyangiitis and microscopic polyangiitis
• Pemphigus vulgaris (reference product)

Human anti-chimeric antibodies are detected in a small proportion of lymphoma patients and more often in autoimmune indications; they have not been clearly linked to loss of efficacy. Comparative programmes use analytical similarity with emphasis on ADCC and CDC potency, a pharmacokinetic study, and a comparative efficacy study in either rheumatoid arthritis or follicular lymphoma, with regulators accepting extrapolation between oncology and autoimmune indications once the Fc functions are shown comparable.

Rituxan was licensed by FDA on 26 November 1997 (BLA 103705) and MabThera authorised in the EU on 2 June 1998 (EMEA/H/C/000165), first for relapsed follicular lymphoma, with the remaining indications added over the following two decades. EU patents expired in 2013 and US patents in 2016 to 2018; Truxima became the first EU biosimilar in February 2017 and the first US biosimilar in November 2018. In India, Dr. Reddy's Reditux, launched in 2007, is widely reported as the first rituximab biosimilar in the world, though it predates the CDSCO permission lists published today.

Sources: Purple Book (S016), EMA medicines data (S017), CDSCO lists (S013, S014); patent expiry and Reditux launch from company and press reports.

Rituximab was where the biosimilar industry learned oncology antibodies: the first Indian products in 2007 and 2013, the first EU oncology antibody biosimilar in 2017, and the first US one in 2018. It is also the molecule where the analytical package matters most, because all three mechanisms of cell killing run through the Fc region. India remains the deepest market, with six domestic manufacturers permitted and two more added in 2025, and the UAE has three EU-sourced products registered.