Biosimilar to Humira, IBI303, Shows Comparable Efficacy and Safety in Phase 3 Trial in China

Treating ankylosing spondylitis (AS) patients with Humira (adalimumab) or a potential biosimilar called IBI303 had comparable effects in reducing disease activity and improving quality of life, and showed a similar safety profile, according to a Phase 3 trial in China.

The study, “IBI303, a biosimilar to adalimumab, for the treatment of patients with ankylosing spondylitis in China: a randomised, double-blind, phase 3 equivalence trial,” was published in the journal The Lancet Rheumatology.

As a biosimilar, IBI303 — developed by Innovent Biologics — is a monoclonal antibody with the same amino acid sequence, formulation, and route of administration of Humira. It also has highly similar chemical properties, potency, pharmacological profile, and activity against TNF-alpha. Therapies targeting this pro-inflammatory molecule show anti-inflammatory activity and prevent disease progression, and are widely used in the treatment of AS.

But while Humira is approved for AS in China, its roughly $2,250 per month price puts it “far beyond affordable for most patients” in that country, Huji Xu, a professor at the School of Medicine of Tsinghua University, said in a press release.

Humira, by AbbVie, is also approved in the U.S. and the EU to treat AS and similar diseases like rheumatoid arthritis and psoriasis, as is the biosimilar Amjevita, by Amgen: it was approved by the FDA in 2016, and by the EMA in 2018. More recently, other biosimilars joined the approval list in the U.S. and the EU.

No biosimilar for Humira exists in China, however.

Aiming to find a more affordable alternative, a double-blind study was conducted at 20 hospitals across the country (NCT02893254). It assessed the efficacy and safety of IBI303 in comparison with Humira in 438 adults (up to age 65).

It also offered the first large-scale, head-to-head Phase 3 comparison of Humira with a biosimilar in people with AS. FDA and EMA approval came from comparative trials in rheumatoid arthritis or plaque psoriasis, with a decision made to cover all indications given to Humira.

A total of 220 patients were treated with IBV303 and the remaining with Humira, given via under-the-skin injection of 40 mg once every two weeks for 22 weeks. All patients had failed to respond to treatment of at least four weeks with nonsteroidal anti-inflammatory drugs, or NSAIDs.

The primary endpoint, or goal, was the ASAS20 response rate at week 24. ASAS20 means an improvement of at least 20% in four domains: patient global assessment of disease, pain, function, and inflammation.

Results showed that 165 (75%) of the patients on IBI303 and 158 (72%) of those on Humira achieved ASAS20, indicating clinical equivalency between the two therapies. Other endpoints further supported this finding, including ASAS20 at week 12, ASAS40 at week 24 — improvement of at least 40% in a minimum of three of the four domains, partial response rates, and BASDAI (a measure of disease activity).

The findings indicate comparable effects in the improvement of physical functions, spinal mobility, disease activity, tendonitis, overall patient assessment, and quality of life.

Treatment with IBI303 was also found to be well-tolerated, with similar safety and immunogenicity — triggering of an immune response — to Humira. A total of 174 (79%) patients taking IBI303 and 178 (82%) on Humira experienced treatment-emergent adverse events, with the most common being elevated liver enzymes levels and upper respiratory infections. Most injection reactions were mild, and were fewer with IBI303 than with Humira.

“This trial showed therapeutic equivalence of IBI303 and adalimumab in the treatment of [AS],” the researchers wrote. According to Xu, the leading principal investigator in the trial, the results also indicate that China-based Innovent “has reached international standard in process development and clinical research of biosimilars.”

An application requesting IBI303’s approval has been granted priority review by China’s National Medical Products Administration based on clinical and preclinical results.

“We are very excited about the publication of IBI303 Phase [3] clinical trial results … which further validated our clinical results, the drug’s efficacy, safety and Innovent’s development capability,” said Michael Yu, founder, CEO and chairman of Innovent.

If approved, IBI303 would become the first biosimilar of Humira in China. “We sincerely hope this high-quality drug could be approved and launched soon so that it can benefit patients and their families,” Yu added.

In an accompanying comment in the same journal, “Biosimilars for rheumatic diseases: China joins the club,” Stanley Cohen, MD, a professor at University of Texas Southwestern Medical Center, said the Phase 3 results “support the approval” of IBI303.

“We hope that the substantial cost reductions noted in some countries will be realised in China too, fulfilling the hope of allowing greater access to these highly effective therapies,” he added.