Although a range of regulatory definitions exist, a biosimilar drug is generally defined as \a biological compound that is highly similar to the reference drug, with no clinically meaningful differences in safety, purity and potency.1,2 In addition, biosimilars can be characterized as reducing healthcare costs while maintaining clinical efficacy and safety outcomes similar to the originator biologic.1
Globally, the number of biosimilars in active development has risen from approximately 70 in 2011 to around 290 in 2016, with approximately 16% of candidates in Phase 1 and 23% of candidates in Phase 3.3 As of September 2016, approximately 197 biosimilars have been launched worldwide, including 23 for the treatment of rheumatoid arthritis (RA).3 RA is the most active indication within the biosimilar pipeline.3 As of May 2017, there were approximately 27 planned/ongoing Phase 1-3 biosimilar RA studies.4 AbbVie’s Humira (adalimumab) is the lead reference biologic with the highest number of biosimilar candidates (27 in global development – preclinical through to Phase III trials), as of September 2016.5
As a consequence of regulatory authorities in some emerging markets having a less rigorous approval pathway for “biosimilars” (i.e. not requiring head to head data that compares their product to the innovator/reference biologic) and thus not meeting the rigorous requirements of established bodies (e.g. US, EU, WHO, etc.) for demonstrating “biosimilarity,” a large number of “similar biologics” are already on the market in some developing countries ‒ by August 2016 India had approved more than 60 “similar biologics”.5
Key Issues for Study Recruitment
As competition for RA patients increases with new, innovative RA therapies in development and an increasing number of RA studies being conducted to assess the efficacy and safety of biosimilar agents, it is becoming more difficult to identify sufficient top tier sites with available patients and resources. Consequently, studies are requiring more sites than would be suggested by historical enrollment data, and/or extended recruitment windows.
Another factor heavily impacting on the most efficient recruitment strategy for RA biosimilar trials is whether to include only biologic naïve vs biologic experienced RA patients. This choice will drive the mix of geographic locations for planned sites, since targeting biologic-naïve patients will require a bias towards countries outside of the most established markets (e.g. US.. and Western Europe), where a significant portion of patients with moderate-to-severe RA have already been treated with biological agents.6 Furthermore, enthusiasm for biosimilars, and to an extent experience/comfort in using them, is much higher in emerging markets where access to the originator biologics has typically been constrained due to cost. In contrast, within North America and Western Europe, there is little incentive for patients to participate in biosimilar clinical studies, since significant levels of reimbursement for biologics already exists through government funding and/or private healthcare insurance.7
As discussed in a previous blog7, the existing pool of RA Investigators is saturated with clinical studies particularly focusing on innovative new treatments. Added to this, a proportion of these investigators will simply not be interested in participating in clinical studies of biosimilars, because their mechanism of action, efficacy and safety profiles are (by definition) well established.
It is obvious that the successful delivery of a biosimilar RA study requires a different approach. We are dedicated to assisting our clients in the development of biosimilars and offers a number of recruitment solutions including:
- A global reach, enabling the targeting of countries in emerging markets where, if required, access to patients naïve to biologics is still greater than in developed markets, and where there is greater enthusiasm for biosimilars.
- A recent global outreach to RA investigators has established a database of >1000 investigators that have confirmed their interest in participating in RA biosimilar studies (see table 1). This database will allow us and our clients to immediately target a receptive group of physicians for future RA biosimilar studies, thus saving considerable time, effort and expense during study-specific site identification activities.
Table 1: Regional Distribution of Sites Interested in RA Biosimilar Studies
|Region||Number of Investigators Interested in Biosimilar Studies|
- Established relationships with specialist recruitment vendors that have the expertise to raise the profile of clinical trials amongst rheumatologists, patients and patient advocacy groups.
- Perhaps an under-utilized resource in historical RA studies, possibly due to disease prevalence, the current RA trial landscape is now demanding their involvement.
- Greater education of physicians currently participating in, or interested in doing clinical research. In particular, the concept of biosimilars and the rigorous type of data required to demonstrate that biosimilars are comparably efficacious and safe in order for them to be licensed for use in RA or other indications.
- Within the U.S., our parent company’s (Labcorp) proprietary database contains >324,000 de-identified RA patients; consequently, we have the ability to pinpoint indication-specific patient densities/hotspots aligned with clusters of treating physicians that are not active investigators. Linking this powerful data to the above physician education initiative offers the potential to identify new Investigators as well as neighboring referral sites. Furthermore, patients utilizing the laboratory facilities of Labcorp are being offered the opportunity to “opt in”, i.e. to be contacted directly about participating in clinical trials. Already, within the infancy of this initiative, >1300 RA patients have opted in.
Early estimates of price discounts that biosimilars could offer in comparison to the innovator product range from 15 to 35%, but there are examples where much higher discounts are being seen.8 Regardless of the extent of the discount, it is evident that biosimilars offer the ability to significantly increase patient access to highly effective treatments for RA. Adherence to the appropriate robust regulatory pathways and employing the right strategic recruitment initiatives will ensure that biosimilar candidates are developed as quickly as possible leading to a much higher proportion of RA patients reaping the benefits offered by a number of biologic treatments.
- Rompas S, Goss T, Amanuel S, et.al. Demonstrating value for Biosimilars: A conceptual framework. Am Health Drug Benefits. 2015 May; 8(3): 129–139.
- US Food and Drug Administration. Drugs: information for healthcare professionals (biosimilars). Updated March 6, 2015. http://bit.ly/2gWwWM3
- Trends – Hot Topic; Datamonitor Healthcare; DMKC0166679; Published 18 November 2016
- Citeline Trialtrove
- Biosimilars in Emerging Markets; Datamonitor Healthcare; DMKC0172273
- Lai Z, La Noce A. Key design considerations on comparative clinical efficacy studies for biosimilars: adalimumab as an example. RMD Open 2016; 2: e000154. doi:10.1136/rmdopen-2015-000154
- Regional Availability of and Reimbursement Models for Biologic Therapies to Treat RA Patients with Moderate to Severe Disease
- Yu B. Am J Manag Care. 2016;22(5):378