Biosimilar Gastroenterology Roundup: October 2019

With new research presented this month, and with new biosimilars in the pipeline that target inflammatory bowel disease (IBD), October was a notable month for biosimilars in the gastroenterology space.

First, this month saw announcements of phase 1 clinical trials for biosimilars referencing Stelara. Ustekinumab, a human interleukin-12 and -23 antagonist, is approved by the FDA to treat Crohn disease and ulcerative colitis, as well as psoriasis and psoriatic arthritis.

NeuClone was the first to announce that it had begun dosing participants in its trial, and Formycon followed shortly thereafter, with news that has begun a phase 1 trial of its own. It remains to be seen which biosimilar developer, if either, will be able to advance its candidate to regulatory submissions first, but Formycon said that it anticipates being able to launch its product in Europe in 2024 and in the United States in 2023.

In other development news, as Amgen awaits the FDA’s decision on its Biologics License Application for APB 710, a proposed infliximab biosimilar, which the drug maker submitted in December of last year, researchers have published detailed results from a phase 1 study of the drug. The pharmacokinetic study met its primary end point of area under the serum concentration—time curve from time 0 extrapolated to infinity, and 90% confidence intervals of the geometric mean ratios for comparisons between the biosimilar and the US reference as well as the EU reference (and the 2 references to one another) fell within the prespecified equivalence margin of 0.80 to 1.25.

While the study did include a bridge between the US and EU references, Amgen has, notably, withdrawn its application for the biosimilar from the European Medicines Agency, citing a change of corporate strategy.

Also on the infliximab front, Celltrion, maker of biosimilar CT-P13 (Inflectra, Remsima) has made strides forward with a proposed subcutaneous form of the biosimilar. After having received a positive opinion for the novel formulation from European Medicines Agency’s Committee for Medicinal Products for Human Use last month for the indication of rheumatoid arthritis, the proposed product got a boost from research presented during the United European Gastroenterology (UEG) Week 2019 meeting, held in Barcelona, Spain.

Findings from a phase 1 pivotal study of the product in patient with IBD, which were presented in a late-breaking abstract session, show that the subcutaneously administered biosimilar was noninferior to the intravenously administered version at week 22, and had comparable safety and efficacy up to week 30. Celltrion plans to file for European regulatory approval for the formulation in IBD in 2020.

This month also saw new data underscoring the safety of the already approved intravenous formulation of CT-P13. Also during UEG Week, researchers presented pooled data from 3 postmarketing studies of the biosimilar in patients with IBD, and reported that the incidence of adverse events of special interest—including serious infections like tuberculosis—was low, and was consistent with the known safety profile of infliximab.

The study presented at UEG Week that may hold the greatest interest for biosimilar stakeholders, however, may be one that addresses multiple biosimilars of infliximab, and the feasibility of switching among them. Researchers reported on 133 patients with IBD being treated at Southampton General Hospital in Southampton, United Kingdom, who switched from CT-P13 to SB2, Samsung Bioepis’ biosimilar, sold as Flixabi in the EU context and Renflexis in the United States. Among these patients, say the researchers, there was no significant difference in treatment persistence versus a historical CT-P13 cohort.

With respect to treatments outside of infliximabs, UEG Week presentations also included data on Samsung Bioepis’ biosimilar adalimumab, Imraldi, particularly with respect to therapeutic drug monitoring. One research team, which studied 87 patients with IBD who switched from the reference Humira to the biosimilar, reported that there was excellent quantitative agreement between adalimumab trough levels before and after the switch. A second team reported that they observed quantitative agreement between 2 measurement kits—a tumor necrosis factor—based ELISA kit and a monoclonal antibody-based ELISA kit—used for monitoring trough levels of the biosimilar.

While biosimilar adalimumab is now widely used in the European Union following its introduction 1 year ago, some stakeholders said this month that they see dwindling opportunities for biosimilars of the blockbuster Humira to make an impact in the US context when they arrive in the market in 2023. A new viewpoint article in JAMA argued that, by 2023, oral therapies, even oral biologics, could well have overtaken Humira in terms of market share, and patients may be unwilling to go back to injectable drugs.

Challenges also appear to be afoot for biosimilars in regulatory territories outside of the United States and Europe; this month, the Canadian Association of Gastroenterology and Crohn’s and Colitis Canada, announced the upcoming publication of a joint statement on biosimilars in IBD, in which they recommend that stable patients not be switched to biosimilars. The organizations also took a stand against automatic substitution, citing what they called a “paucity of evidence” on the topic.

Such a lack of confidence in biosimilars on the part of providers could pose a barrier to uptake. In fact, this month, a survey of physicians revealed that providers think their own lack of confidence is the biggest barrier to widespread adoption.

The Canadian position paper comes at the same time as new research has shown that, as public coverage for infliximab and adalimumab grew in Ontario, Canada, the prevalence of hospitalizations related to Crohn disease (CD) fell by more than 30%. Surgeries for CD fell by just under 40%.

The benefits of biologic access for patients with IBD are notable in this context because, earlier this year, a Canadian advisory council recommended the use of biosimilars in particular to help Canada create a universal, single-payer public health system for pharmaceutical coverage.

Meanwhile, in the United States, stakeholders continue to grapple with the skyrocketing cost of biologics that can hinder patient access. A Kaiser Family Foundation analysis found that, between 2016 and 2017, 60% of drugs in the Medicare Part D drug spending dashboard, like Humira, had list prices hikes that exceeded the rate of inflation. Current policy proposals have suggested that Medicare could save money if drug makers limit price increases to the rate of inflation, but some have argued that drug makers could offset such changes by simply increasing launch prices or reducing rebates.