The FDA has approved the first biosimilar version of the interleukin-6 (IL-6) blocker tocilizumab, to be marketed as Tofidence and with indications for rheumatoid arthritis (RA), systemic Juvenile Idiopathic Arthritis (sJIA), and polyarticular juvenile idiopathic arthritis (pJIA).

Manufactured and marketed by Biogen with the formal generic name of tocilizumab-bavi, the new product will compete with Roche/Genentech’s blockbuster original, Actemra.

But Tofidence won’t sport all the indications that Actemra now carries. Missing are conditions including: giant cell arteritis, interstitial lung disease arising from systemic sclerosis, cytokine release syndrome, and most notably, COVID-19. As well, Tofidence is approved only in an intravenous formulation, whereas Actemra also comes in prefilled syringes for subcutaneous administration, which is how RA and JIA patients typically take it.

Actemra has reportedly been earning upwards of $3 billion annually for its makers, but Tofidence and another tocilizumab biosimilar sold by Fresenius Kabi called Tyenne, approved 2 weeks ago in Europe, are expected to take a substantial cut of the market. This past summer, Roche sued Biogen alleging patent infringement in an attempt to keep Tofidence off the market. For its part, Biogen said it is “currently evaluating the potential launch timeline for Tofidence in the U.S.”

Tyenne’s European approval gave it all the indications currently enjoyed by Actemra, and includes prefilled syringes for subcutaneous injection, but Fresenius Kabi has given no indication that it plans to seek U.S. authorization.

In announcing the approval, the FDA emphasized that Tofidence was the first biosimilar drug of any kind to be indicated for sJIA.

The agency also confirmed that Biogen had successfully shown both pharmacokinetic and clinical equivalence to the original version. However, the new product is not listed as interchangeable with Actemra, in the sense of freely switching back and forth between them. (On the other hand, new FDA guidance is expected to weaken the distinction by prohibiting makers from advertising interchangeability status.) Tofidence was initially developed by Bio-Thera, with Biogen buying marketing and manufacturing rights for most of the world (China, Hong Kong, Macau, and Taiwan excepted) in April 2021.

Tocilizumab was the first IL-6 inhibitor to reach the market, and has established that this is an effective target for a range of rheumatologic conditions. Other IL-6 blockers have since joined the competition, including sarilumab (Kevzara) and satralizumab (Enspryng). Its role in RA, the biggest market among the approved indications, is as a second-line treatment after conventional synthetic anti-rheumatic drugs such as methotrexate have proved inadequate. Most RA patients eventually need second-line therapy, although there are numerous other choices including tumor necrosis factor blockers and oral Janus-associated kinase inhibitors.

IL-6 also emerged as a potential target for severe COVID-19 after studies showed that it was a key player in the excessive immune response to infection. Roche/Genentech won an FDA approval for this indication, but with relatively few COVID cases now reaching such severity, tocilizumab is not often used.