Hulio Receives EU Marketing Authorization, Entering the Biosimilar Competition for Humira
EU Approval and Product Profile
The European Union approved the marketing authorization for Hulio (adalimumab) on September 17, 2018, and Mylan began its European sales in October of the same year. Hulio is a monoclonal antibody that blocks tumor necrosis factor alpha (TNF-α) and is a biosimilar referencing AbbVie's (ABBV) Humira (adalimumab). It can be used for major indications of Humira, including rheumatoid arthritis, psoriasis, Crohn's disease, and ulcerative colitis, targeting a broad market for immune disorders beyond single diseases. As the product transitions from approval to commercialization, the competitive focus has shifted from clinical development to pricing, tendering, and distribution capabilities.
Equivalence Proven in Phase 3 Clinical Trials
In a Phase 3 clinical trial involving 730 patients with rheumatoid arthritis inadequately controlled by methotrexate, the ACR20 response rate at 24 weeks was 74.1% for Hulio and 75.7% for Humira. The 95% confidence interval for the treatment difference was -7.9% to 4.7%, falling within the predefined equivalence range. Structural, purity, and biological activity, as well as pharmacokinetics, also showed high similarity. In an extension study, no clinically significant differences were observed in efficacy, safety, or immunogenicity after switching between Humira and Hulio. These results support the development of biosimilars by reinforcing prescription switching and extrapolation of indications, rather than demonstrating superiority through a new mechanism.
Regulatory History and Competitive Landscape
The EMA Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion on July 26, 2018, and EU-wide marketing authorization became effective on September 17. The approval was granted through a centralized EMA review process, without a separate FDA advisory committee (AdComm) procedure, and the regulatory phase is now approval and sales. In Europe, Amgen's (AMGN) Amgevita, Samsung Bioepis and Biogen's (BIIB) Imraldi, and Sandoz's Hyrimoz are direct competitors, while the existing standard of care includes Humira and other TNF inhibitors such as infliximab and etanercept. The simultaneous market entry of multiple products has shifted the key factors for market share to tender pricing and supply stability in individual countries, rather than clinical differentiation.
Market Potential and Rights Transfer
Humira recorded global sales of USD 18.427 billion in 2017, with USD 6.066 billion in sales outside the U.S., forming a large revenue base for biosimilars to target. Mylan paid USD 25 million upfront and USD 10 million as an approval milestone to Fujifilm Kyowa Kirin Biologics and also agreed to royalty payments tied to net sales. Following Mylan's succession by Viatris (VTRS), the biosimilar business, including Hulio, was transferred to Biocon Biologics for up to USD 3.335 billion, integrating commercial rights and sales infrastructure. Biocon has secured the foundation to directly recognize product sales and profits, but strong price reductions and tender competition in Europe limit the direct translation of revenue growth into high margins.
Hulio is a TNF-α biosimilar in the approval and sales phase, directly targeting the European market opportunity following the expiration of Humira's patent, which recorded global sales of USD 18.427 billion in 2017. The Phase 3 ACR20 response rates were 74.1% for Hulio and 75.7% for Humira, with a 95% confidence interval of -7.9% to 4.7%, meeting equivalence criteria and providing a scientific basis for prescription switching. In the short term, tender competition with Amgevita, Imraldi, and Hyrimoz is pressuring drug pricing and AbbVie's Humira sales outside the U.S., offering patients and healthcare institutions improved treatment access and cost savings. In the medium to long term, Biocon (BIOCON.NS) has internalized the distribution and sales of Hulio through the acquisition of Viatris' biosimilar business, but profitability remains dependent on tender market share and supply cost per country. For researchers and the industry, post-multiple-switch immunogenicity data, supply reliability, and non-price differentiators such as high-concentration and sodium citrate-free formulations are key indicators for subsequent competition.
Source: EMA (ema)