Biosimilar for Crohn's Noninferior to Adalimumab

Maureen Salamon

December 14, 2019

In patients with moderate or severe active Crohn's disease, the adalimumab biosimilar BI 695501 (Boehringer Ingelheim) is as safe and effective as adalimumab (Humira, AbbVie), new results from a phase 3 trial suggest.

This is the first randomized controlled study to compare the biosimilar with adalimumab specifically in Crohn's patients, opening the door to less-costly treatment options for this group, said lead investigator Stephen Hanauer, MD, from Northwestern University in Chicago, who is cochair of Advances in Inflammatory Bowel Diseases (AIBD) 2019.

Previously, clinicians had to rely on trials that showed the noninferiority of BI 695501 to adalimumab in patients with rheumatoid arthritis to determine dosing in patients with Crohn's disease, he told Medscape Medical News. Gastroenterologists wanted to see a study in inflammatory bowel disease; that's why this research was done, he added.

Once a biosimilar is approved by the US Food and Drug Administration (FDA) for one indication, it is automatically approved for all indications in a category. The BI biosimilar was approved for rheumatoid arthritis in 2017, meaning that it is approved for Crohn's disease as well.

But the biosimilar can't be marketed for Crohn's disease until various patent issues are legally resolved, Hanauer explained.

Once that happens — a process he predicts will take 1 to 3 years — "by virtue of competition, it will hopefully drive costs down," he said. "Then more individuals will have access to this highly effective class of medication."

Hanauer presented results from the randomized, double-blind, multicenter trial comparing BI 695501 with adalimumab in 147 adults who had had moderate or severe active Crohn's disease for at least 4 months at AIBD 2019 in Orlando.

Patients were randomized 1:1 to receive BI 695501 or adalimumab, with a 160 mg loading dose on day 1, 80 mg on day 15, and 40 mg every 2 weeks thereafter. After 4 weeks, responders continued on a maintenance phase for up to 24 weeks, after which the adalimumab group was switched to the biosimilar. Participants were also stratified by previous use of infliximab and their Simple Endoscopic Score for Crohn Disease.

Effectiveness over 4 weeks was analyzed using Crohn's Disease Activity Index (CDAI) scores. The primary end point was a decrease in CDAI scores of at least 70 points; secondary end points looked at week 24 CDAI response and clinical remission.

CDAI response rates at week 4 were similar in the two groups, with scores decreasing at least 70 points in 89.7% of the BI 695501 group and 94.4% of the adalimumab group. The percentage of patients showing CDAI improvements of at least 100 points and absolute CDAI scores lower than 150 was also similar in the two treatment groups, Hanauer reported.

A safety analysis showed no significant differences in the two groups and no unexpected outcomes at week 24. Infection rates were comparable in the biosimilar and adalimumab groups (13.9% vs 14.7%). Injection-site reactions were observed in 4% of adalimumab patients but in 0% of biosimilar patients.

One limitation of the research, said Hanauer, is that biosimilars are evaluated with the same criteria used to approve the original reference drug in a disease setting. In this case, the study's primary end point mirrored that used to approve adalimumab in Crohn's disease nearly 2 decades ago.

"Nowadays, studies are going beyond CDAI and look at parameters such as endoscopic improvement, which was not part of the original approval," he said, noting that this wasn't done in the current study.

I think the greatest impact is that this will present a tremendous cost savings.

Other physicians were enthusiastic about the new findings. Miguel Regueiro, MD, from the Cleveland Clinic, said the clinical impact could be "huge."

"Thousands and thousands of adalimumab patients may actually look to a biosimilar" for Crohn's disease relief, "which is not something that's been done to this point," said Regueiro, who is cochair of the conference.

"I think the greatest impact is that this will present a tremendous cost savings," he told Medscape Medical News. "The way biosimilars are currently hitting the US market, patients will likely be switched to them at some point. Since this is noninferior to adalimumab, there's comfort in knowing the efficacy and safety and pharmacokinetics of the biosimilar are the same."

Although the study's primary outcome looked at the efficacy of BI 695501 over 4 weeks, which is "a nanosecond in IBD care," Raymond Cross, MD, from University of Maryland in Baltimore, said that he doesn't "anticipate surprises" when long-term data are eventually obtained.

"I think these studies are important because they reassure providers who have concerns about the biosimilar, not only about the efficacy of starting it in [patients naïve to biologics], but also in switching," Cross told Medscape Medical News.

But patients may be skeptical of switching to a biosimilar if their Crohn's is under control using a biologic, he added, so it might be harder to convince them if the cost savings isn't passed on to them, but is absorbed by their health insurer.

"It's certainly likely there's cost savings to society as a whole, but unfortunately, it's not necessarily to the patient," he explained.

Advances in Inflammatory Bowel Diseases (AIBD) 2019: Abstract P052. Presented December 13, 2019.

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