When Will Biosimilars Be Available for Inflammatory Bowel Disease?

Biosimilars face scrutiny before they can be indicated for inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis.

It is a time of mixed emotions in the world of biological therapies. On one hand, the emergence of biological agents has revolutionized treatment options for several debilitating immune-mediated inflammatory diseases, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriasis, psoriatic arthritis, Crohn’s disease (CD), and ulcerative colitis (UC).

On the other hand, explained a review in Intestinal Research, the prohibitive cost of innovator biologics along with regulatory issues inhibiting the approval of biosimilars have served to limit access to the clinical potential of these drugs.

Authors of the review pointed out that the growing incidences of CD and UC increase the number of chronic inflammatory bowel disease (IBD) patients who could benefit from biologic therapy.

Especially when applied early in the course of immune-mediated inflammatory diseases, tumor necrosis factor alpha (TNF-a) antagonists—adalimumab, certolizumab, etanercept, golimumab, and infliximab—have been associated with clinical remission; less structural damage; reduced need for corticosteroids, hospitalization, and surgery; and improved quality of life for patients.

They explained, however, that the duration and cost of biologics research and development keeps their prices prohibitively high for many patients, while testing and regulatory requirements limit how quickly biosimilar alternatives are being made available.

Can a New Biosimilar Be Indicated for Inflammatory Bowel Disease?

A new biosimilar, CT-P13, was recently developed as an alternative to the originator infliximab. CT-P13 has been approved in several countries, based on only 1 equivalence trial for RA supplemented by a pharmacokinetic study on AS, the authors noted. Of the 6 indications for infliximab, however, RA is probably the least sensitive model to demonstrate differences in efficacy between CT-P13 and infliximab. Therefore, additional testing is needed before CT-P13 can pass FDA approval to be indicated for IBD.

Additional hurdles stand in the way of biosimilar approval for IBD. Immunogenicity is a primary safety concern, the review said. Especially for CD, the incidence of immunogenicity with biologic use is quite high (61%) compared with the rate for RA (under 10%).

Authors emphasized that demonstrating interchangeability will be an even greater challenge than demonstrating biosimilarity. A discouraging study comparing epoetin-a with its biosimilar SB309 as treatments for renal anemia showed that switching to the biosimilar resulted in a 10% to 15% dose increase and a 5% decrease in hemoglobin concentration, whereas, switching back to epoetin-a reduced the dose almost by 10% and raised hemoglobin levels by 10%.

Clinical Evidence for IBD Biosimilars

The review concluded that to make biosimilars available to treat IBD, well designed, prospective randomized non-inferiority trials are needed to assess efficacy, safety, immunogenicity, and interchangeability with their branded counterparts.

Authors offered data from their own research in Korea, in which they conducted a retrospective multicenter study of the clinical efficacy and safety of CT-P13. In a group of 32 anti-TNF naïve CD patients, clinical response rates with CT-P13 at week 8, 30, and 54 were 90.6%, 95.5%, and 87.5%, respectively.

CD remission rates were 84.4%, 77.3%, and 75%, respectively. For a group of 42 anti-TNF naïve UC patients, clinical response rates with CT-P13 were 81%, 91.3%, and 100%, respectively; and UC remission rates were 38.1%, 47.8%, and 50%, respectively.

Looking at interchangeability among 27 CD patients and 9 UC patients, they found efficacy maintained in 92.6% of CD patients (25 of 27) and 66.7% of UC patients (6 of 9). There were no infusion reactions or serious adverse events among this small patient population.

The review referenced 2 other studies thus far, which suggested that biosimilars may offer comparable efficacy, safety, and immunogenicity for IBD patients.