The US FDA approval of Fresenius Kabi’s Tyenne®, the first Tocilizumab biosimilar with both intravenous and subcutaneous formulations, is a breakthrough in bringing high-quality, affordable, and accessible autoimmune treatment options to patients and healthcare providers. The biosimilar has been launched across the globe in more than 10 countries, with plans to launch in many more countries between 2024 and 2025.

Tocilizumab, marketed as Actemra®, is an immunosuppressive anti-IL-6R humanised monoclonal antibody. It is approved for treating COVID-19, systemic juvenile idiopathic arthritis, and rheumatoid arthritis. The licensing for its development was granted by Hoffmann-La Roche to Osaka University and Chugai Pharmaceutical. Initially introduced in 2003, Actemra® is available in two formulations: subcutaneous (SC) and intravenous (IV).

It received approval in Europe in January 2009 and in the US in January 2010. In FY 2023, Actemra® had generated worldwide sales of 2.6 billion CHF. Additionally, it has received emergency authorization for use in Ghana and the United States, and provisional approval in Australia. It is also approved for defined patient groups hospitalized with severe or critical COVID-19 in several countries including the European Union, Ecuador, Honduras, Japan, Myanmar, Peru, the United Kingdom, and Ukraine, as recommended by the World Health Organization (WHO).

In the US, Actemra® was protected by US5795965, which expired in April 2019, and US5851793, which expired way before in December 2015. These two patents can be considered as the primary patents, serving as the base for generating a patent thicket. In Roche’s annual report of 2022, it was claimed that the basic and primary patents have expired and that they expect biosimilar entries by H2-2023.

In July 2023, Genentech, Inc., Hoffmann-La Roche, Inc., and Chugai Pharmaceutical Co. Ltd. initiated a BPCIA litigation against Biogen MA Inc. and Bio-Thera Solutions, Ltd. in the District of Massachusetts. The litigation revolved around Biogen’s pursuit of FDA approval for ‘BIIB800,’ a proposed biosimilar to Genentech’s drug Actemra® (tocilizumab). According to Genentech’s complaint, Bio-Thera manufactures BIIB800 for Biogen and would be involved in its importation into the United States. Genentech’s complaint detailed the exchanges between the parties during the “patent dance,” highlighting Biogen’s alleged failure to provide sufficient information about the manufacturing process as required by the BPCIA. Genentech claimed that Biogen’s incomplete information hindered their assessment of potential infringement. The asserted patents covered various procedures, therapeutic modalities, antibody subtypes, and formulations. The asserted patents were U.S. Patent Nos. 7,332,289; 7,521,052; 8,398,980; 8,512,983; 8,574,869; 8,734,800; 9,714,293; 9,902,777; 10,017,732; 10,336,983; 10,501,769; 10,662,237; 10,676,710; 10,744,201; 10,829,732; 10,982,003; 11,021,728; 11,078,294; 11,136,610; and 11,377,678.

Genentech sought several forms of relief, including an infringement judgment, statutory relief, damages (including lost profits or a reasonable royalty), an accounting of damages, a declaration of case exceptionality, and attorneys’ fees. Additionally, Genentech requested a jury trial. Ultimately, a settlement was reached in December 2023.

Following this, the FDA has approved two biosimilars to date. The initial one, Tofidence® (tocilizumab-bavi), a product of Biogen and Bio-Thera Solutions, obtained FDA clearance in September 2023. However, it is solely authorized for intravenous (IV) administration. It is approved for the treatment of moderately to severely active Rheumatoid arthritis, Polyarticular juvenile idiopathic arthritis and Systemic juvenile idiopathic arthritis in USA.

The second biosimilar, manufactured by Fresenius Kabi under the name Tyenne® (tocilizumab-aazg), offers the flexibility of subcutaneous or intravenous (IV) administration. It is launched for Rheumatoid arthritis, Juvenile rheumatoid arthritis, and Giant cell arteritis in USA.

Other biosimilars which are being developed, are as follows:

The approval of Actemra® biosimilars represents a significant step forward in healthcare accessibility and affordability. With biosimilars on the market, patients can benefit from increased availability of this vital medication, potentially improving adherence to treatment regimens and overall health outcomes. Moreover, biosimilars undergo rigorous testing to ensure safety and efficacy, providing patients with confidence in their treatment options.

Actemra®, a cornerstone immunosuppressive medication, plays a crucial role in managing various medical conditions, including rheumatoid arthritis and severe cases of COVID-19. Its widespread use and effectiveness are evident in its substantial global sales. The availability of biosimilars presents promising opportunities to expand access to Actemra®, especially in regions where cost may have previously been a barrier to treatment.

Rheumatoid arthritis (RA), a chronic inflammatory disease caused by an autoimmune response, leading to joint swelling and pain, often results in severe disability. Biologic disease-modifying anti-rheumatic drugs (DMARDs) have become a mainstay in RA treatment. However, their high cost poses a barrier to access for many patients and healthcare systems. In response, biosimilar DMARDs (biosimilars) have been developed to offer a more affordable alternative, aiming to expand access to effective biologic therapy.

Along with Actemra® and its biosimilars, there are multiple other biosimilar products of various drugs approved for Rheumatoid arthritis. As of May 2024, a total of 29 biosimilars for the treatment of RA have been approved cumulatively in the US and EU, as follows. These biosimilars references biologics such as Adalimumab, Etanercept, Infliximab and Rituximab.

Patient access to rheumatoid arthritis biosimilars, thus, presents a promising opportunity to enhance the affordability and availability of effective treatment options. Biosimilars offer comparable efficacy and safety to their reference biologic drugs but at a reduced cost, potentially alleviating financial burdens for patients and healthcare systems. By providing more affordable alternatives to biologics, biosimilars have the potential to expand access to essential therapies for individuals with rheumatoid arthritis, particularly those facing economic challenges or limited insurance coverage. However, achieving widespread adoption and acceptance of biosimilars requires addressing concerns related to their interchangeability, safety, and efficacy. Healthcare providers play a crucial role in educating patients about the benefits and risks of biosimilars and in fostering confidence in these treatments. Additionally, policy interventions may be necessary to incentivize the use of biosimilars and promote competition in the biologics market, ultimately improving access to high-quality care for individuals living with rheumatoid arthritis.

In addition to this, the regulatory approvals for emergency use of Actemra® in multiple countries underscore its importance in addressing urgent medical needs. Ongoing clinical trials for additional Actemra® biosimilars demonstrate continued interest and investment in improving patient care and expanding treatment options.

In conclusion, Actemra® remains a vital tool in the treatment of critical medical conditions, and the emergence of biosimilars offers new avenues for enhancing accessibility and affordability. By leveraging the benefits of biosimilars, healthcare providers can better meet the diverse needs of patients worldwide, ultimately improving outcomes and quality of life.