Roche Submits Third Indication NDA for Tocilizumab in China

On July 8, the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration released its latest public notice, indicating that Roche has submitted a marketing application for a new indication of tocilizumab injection, an IL-6 monoclonal antibody. This marks the third time tocilizumab has been submitted for market approval in China, following previous submissions in 2010 and 2016. The product has previously been approved in China for the treatment of rheumatoid arthritis (RA) and systemic juvenile idiopathic arthritis (sJIA). Globally, tocilizumab has also been approved for the treatment of conditions such as cytokine release syndrome (CRS), giant cell arteritis (GCA), and active polyarticular juvenile idiopathic arthritis (pJIA). The submission of this third marketing application in China suggests that tocilizumab is poised to gain a third approved indication in the country.

Source: CDE Official Website

Tocilizumab is a recombinant humanized monoclonal antibody against the human interleukin-6 (IL-6) receptor, expressed in mammalian cells (CHO). It exerts its therapeutic effect by inhibiting the activity of the IL-6 receptor. IL-6 is a pro-inflammatory cytokine whose release can trigger a cascade of downstream pro-inflammatory responses. Tocilizumab blocks the binding of IL-6 to both soluble and membrane-bound IL-6 receptors, thereby inhibiting IL-6 signal transduction and reducing pathological inflammatory responses.

Globally approved for the treatment of various immune-mediated diseases

It is reported that tocilizumab is the first humanized IL-6 receptor antagonist approved for administration via both intravenous infusion and subcutaneous injection. Since 2009, this product has been sequentially approved for marketing in multiple countries and regions, including the European Union, the United States, and Japan. The approved indications are as follows:

Adult patients with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate response to treatment with at least one other disease-modifying antirheumatic drug (DMARD);

Adult-onset giant cell arteritis; tocilizumab thus became the first FDA-approved therapeutic product specifically indicated for GCA.

Active polyarticular juvenile idiopathic arthritis, indicated for patients aged 2 years and older;

Active systemic juvenile idiopathic arthritis, indicated for patients aged 2 years and older;

Indicated for pediatric patients aged 2 years and older and adult patients who develop severe or life-threatening cytokine release syndrome (CRS) following treatment with CAR-T cell therapy;

In addition to the aforementioned approved indications, Roche is advancing tocilizumab for the treatment of a broader patient population. Notably, clinical studies evaluating this product for the treatment of systemic sclerosis have progressed to late-stage development.

Tocilizumab in China

Tocilizumab was first approved in China in 2013 for the treatment of rheumatoid arthritis (RA) under the brand name Actemra. In 2016, it received approval for a new indication—systemic juvenile idiopathic arthritis (sJIA)—based on an exemption from Phase III clinical trials, thereby becoming the first biologic agent approved in China for the treatment of sJIA. According to the Drug Clinical Trial Registration and Information Publicity Platform, multiple studies involving tocilizumab have been registered in China, covering indications such as systemic juvenile idiopathic arthritis and rheumatoid arthritis.

According to Roche’s previous announcement, in August 2019, tocilizumab was officially included in the National Reimbursement Drug List of China for second-line treatment of systemic juvenile idiopathic arthritis, as well as for patients with a clear diagnosis of rheumatoid arthritis (RA) who have shown less than a 50% reduction in disease activity after 3–6 months of treatment with conventional DMARDs.

In addition, several pharmaceutical companies in China are currently engaged in the development of tocilizumab biosimilars, including Bio-Thera Solutions and Jinyu Biopharma. In May this year, the Center for Drug Evaluation (CDE) released the “Guidelines for Clinical Trials of Tocilizumab Injection Biosimilars (Draft for Comment)” to further promote the development of biosimilars for this product.

Phase 3 Study on COVID-19 Treatment to Announce Results This Summer

Studies have shown that in some patients with severe COVID-19, elevated IL-6 levels are significantly associated with the occurrence of a "cytokine storm." When a "cytokine storm" occurs, it can lead to severe lung injury and may be life-threatening. Based on this, tocilizumab, an IL-6-targeting agent, has been hoped to improve pulmonary inflammation.

Currently, Phase 3 studies of tocilizumab for the treatment of severe coronavirus disease 2019 (COVID-19) patients are underway in multiple countries. According to Roche’s first-quarter financial report, the results of these studies are expected to be released in early summer 2020. Notably, in April this year, Roche received $25 million in support from the U.S. Biomedical Advanced Research and Development Authority (BARDA) to accelerate the Phase 3 clinical trials of tocilizumab for treating COVID-19 patients.

Roche’s submission of a new indication marketing application for tocilizumab in China is expected to expand the product’s indicated uses. In addition to systemic juvenile idiopathic arthritis and rheumatoid arthritis, tocilizumab has the potential to benefit patients with giant cell arteritis, cytokine release syndrome, and active polyarticular juvenile idiopathic arthritis. We wish the product a smooth subsequent registration process, enabling more patients to benefit from this medication at an earlier date.

References:

[1] Center for Drug Evaluation, National Medical Products Administration of China. Retrieved July 7, 2020, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=21#

[2] Roche’s Actemra® (tocilizumab) approved by the FDA for the treatment of cytokine release syndrome induced by CAR-T therapy, Retrieved August 31, 2017, from https://endpts.com/gsk-licenses-ionis-experimental-hep-b-treatments-in-up-to-262m-deal/

[3] Okuda. (2018). Review of tocilizumab in the treatment of rheumatoid arthritis. Biologics: Targets & Therapy DOI:10.2147/BTT.S1828

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