Adalimumab biosimilar noninferior to reference product for Crohn’s disease

The adalimumab biosimilar BI 695501 shows similar efficacy and safety profile as its reference product in patients with moderate-to-severe Crohn's disease (CD), according to a phase III study recently presented at the Advances in Inflammatory Bowel Diseases (AIBD) 2019 Conference.

While BI 695501 was previously shown to be bioequivalent to the adalimumab reference product for rheumatoid arthritis, it has not been specifically tested in patients with CD. The current study represents the first randomized trial to do so for the indication of CD, said lead investigator Dr Stephen Hanauer from Northwestern University in Chicago, Illinois, US.

“In a primary analysis based on efficacy data up to week 4, BI 695501 demonstrated noninferior efficacy compared with adalimumab reference product in patients with active CD,” he reported.

At 4 weeks, the primary endpoint of CD Activity Index (CDAI) response, defined as a ≥70-point decreased score, occurred in similar proportion of patients in the biosimilar and the adalimumab groups (89.7 percent vs 94.4 percent). The corresponding relative risk (RR) was 0.945 (95 percent confidence interval [CI], 0.856–1.044), thus meeting the criteria for the exploratory noninferiority margin. [AIBD 2019, abstract P052]

The per-protocol analysis also showed similar rates of CDAI response between the two groups (RR, 0.941, 95 percent CI, 0.859–1.030), consistent with the results of the primary analysis. 

In addition, treatment effects were comparable between both groups in terms of improvements of ≥100 points in CDAI scores and absolute CDAI scores of <150 during the induction phase.  

“Moreover, safety profiles up to 24 weeks were similar between treatment arms,” observed Hanauer.

There were no significant differences in the incidence of adverse events (AEs) of any grade (41.7 percent vs 36.0 percent) and serious AEs (2.8 percent vs 4.0 percent) with no unexpected safety signals at 24 weeks.

AEs of special interest were uncommon in both groups (1.4 percent vs 2.7 percent). Specifically, infection rates were similar, reported in 13.9 percent of the patients receiving the biosimilar and 14.7 percent of those on adalimumab. Injection site reactions occurred more frequently with adalimumab (4.0 percent) compared with none in the biosimilar group.  

The phase III, double-blind, multicentre, noninferiority trial involved 147 patients with active CD who were randomized 1:1 to receive the biosimilar BI 695501 or the reference EU-approved adalimumab with the following dosing regimen: loading dose of 160 mg on day 1, 80 mg on day 15, followed by 40 mg every 2 weeks subsequently. Those who showed response to treatment after 4 weeks continued on maintenance therapy up till 24 weeks, at which point patients receiving the adalimumab reference product were switched to BI 695501.

Patients were stratified according to whether they had previous exposure to infliximab and baseline Simple Endoscopic Score for CD. Both groups were balanced in terms of baseline characteristics. In general, the population showed high response and remission rates.  

According to Hanauer, the finding that BI 695501 was noninferior to adalimumab specifically in CD would allow for less costly treatment options for CD patients.