New Biosimilar for Adalimumab in Rheumatoid Arthritis

Damian McNamara

June 15, 2017

MADRID — For patients with rheumatoid arthritis, treatment efficacy at 24 weeks is similar with adalimumab (Humira, AbbVie) and the biosimilar FKB327, according to results of a phase 3 study.

In addition, the safety profiles were comparable, with no new concerns arising, said Rieke Alten, MD, PhD, from the Medical University of Berlin in Germany.

"Overall, these results demonstrate that FKD327 is a candidate biosimilar to the adalimumab reference product," Dr Alten said here at the European League Against Rheumatism (EULAR) Congress 2017.

The study participants were recruited at 105 sites in 12 countries. All had moderate to severe rheumatoid arthritis for 3 months or longer and were poorly controlled on methotrexate. Participants also had elevated C-reactive protein levels of 10 mg/L or greater. No previous adalimumab treatment was allowed, but a history of one tumor necrosis factor inhibitor or biologic was permitted.

Treatments were administered as 40-mg subcutaneous injections every other week while patients continued receiving methotrexate. A total 366 people were randomly assigned to receive FKB327, and another 362 to receive the reference product.

These results demonstrate that FKD327 is a candidate biosimilar to the adalimumab reference product. Dr Rieke Alten

At 24 weeks, American College of Rheumatology (ACR) 20 response rates were 74.4% for the FKB327 group and 75.7% for the adalimumab group, meeting the study's primary endpoint for bioequivalent efficacy.

A key secondary endpoint was change in Disease Activity Score 28 using C-reactive protein (DAS28-CRP) at week 24.

"DAS28-CRP is the same over time — all the curves are overlapping," Dr Alten reported, further demonstrating the comparability of FKB327 and the reference product.

In addition, the proportion of patients achieving the additional secondary endpoints of ACR20, ACR50, and ACR70 over time "were totally comparable between the two treatment groups," she added.

A Patient Death

The adverse event profile was similar for both drugs, with pharyngitis, respiratory infections, and urinary tract infections the most common adverse events reported. Discontinuations in both groups were very low, said Dr Alten.

There was one death in the FKB327 group. A man from Romania who had tested negative for tuberculosis (TB) before study entry was found to be positive when retested at week 22. He developed gastric bleeding leading to his death, study investigators reported.

This case of disseminated TB might have been treatment related, Dr Alten added.

There were very low numbers of active TB overall, with one case reported in the FKB327 group and three in the adalimumab group. "This could be attributed to the countries where the study was performed, including some where TB is highly endemic," she explained.

In addition, immunogenicity findings were comparable between the treatment groups, with approximately 60% of participants in each group positive for antidrug antibodies, Dr Alten reported.

The next step in the research is to evaluate the results of the ongoing open-label extension of the phase 3 trial to look at long-term data and get more insight into the effect of switching to the biosimilar, she added.

Audience member Jonathan Kay, MD, from UMass Memorial Medical Center in Worcester, Massachusetts, complimented the presentation, but also raised a question about antidrug antibody levels seen in the study.

"You pointed out that the immunogenicity was comparable, but it looked like the biosimilar had a higher proportion of antidrug antibodies than the reference product," he said during the question-and-answer period.

High Antidrug Antibody Levels

"This is unusual for a biosimilar, in that most biosimilar studies show, if anything, a lower incidence of antidrug antibodies," Dr Kay explained.

"I don't agree with the expectation that normally the rate of antidrug antibodies is lower," Dr Alten replied.

In addition, although antidrug antibodies were a couple of percentage points higher in the biosimilar group, it was not statistically significant, she added. "There really is no difference in the frequency of the antidrug antibodies."

A second meeting attendee pointed out that the proportion of patients testing positive for antidrug antibodies was high in both groups. He suggested that the assay the investigators used could have been very sensitive.

"The assay was very sensitive," said Dr Alten. "These assays are in evolution. As our experience is growing, the assays are also growing better and better, and showing more and more."

From a clinical point of view it's pretty exciting that another adalimumab biosimilar will be coming out. Dr Jackie Nam

"This study adds to the body of work in biosimilars. From a clinical point of view, it's pretty exciting that another adalimumab biosimilar will be coming out," said session moderator Jackie Nam, MD, from the Leeds Institute of Rheumatic and Musculoskeletal Medicine in the United Kingdom. "It means there will be more new treatments out on the market."

However, "these are important questions in biosimilars as they come out: efficacy, the effect of switching, and the antidrug antibodies," she told Medscape Medical News.

She added that potential differences in antidrug antibodies between agents or between assays warrants a closer look in the future.

Dr Alten is a consultant for Fujifilm Kyowa Kirin Biologics, which funded the study. Dr Kay has financial relationships with AbbVie, Alexion, Amgen, Ardea Biosciences, AstraZeneca, BI, BMS, Crescendo Bioscience, Eli Lilly, Epirus, Genentech, GSK, Hospira, Janssen, MSD, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Roche, and UCB. Dr Nam has disclosed no relevant financial relationships.

European League Against Rheumatism (EULAR) Congress 2017: Abstract OP0021. Presented June 14, 2017.

Follow Medscape Rheumatology on Twitter @MedscapeRheum and Damian McNamara @MedReporter

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