It is essential that a biosimilar can gain approval as close to when the innovator product comes off patent and or ahead of competitors that are developing biosimilars for the same reference product. Completing the clinical trial in a timely manner is critical, so that the sponsor is able to submit BLA/MAA as soon as possible, obtain approval and gain market share. Timely study start-up and enrollment are key components to successfully achieving this objective.

ICON was awarded a Global Phase III study (>700 patients) in Non-Small Cell Lung Cancer (NSCLC) patients for a biosimilar bevacuzimab with First Patient In (FPI) planned for May 2015 and the approved Enrollment timeline outlined from 18-May-2015 to 13 Jan 2017 (20 months). During study conduct, a 2-month hold on screening was imposed due to availability of the reference product.

Country and site selection in a highly competitive landscape for sites and patients

Oncology drug development is a highly competitive environment and it is even more pronounced for biosimilar development. This makes identifying suitable countries and sites particularly important. For the biosimilar NSCLC study, ICON made a thorough analysis of the competitive NSCLC clinical trial environment to be able to place the study in countries where the study could reasonably be managed. Secondly, ICON looked at regions where patient access to the innovator product is limited, for example, due to lack of reimbursement. This helped identify regions and countries where competition was manageable and the originator product is not readily available. Subsequently, we contacted sites within these countries, from our Investigator database where we had existing relationships and proven recruitment potential in previous NSCLC trials. This step-wise approach helped us to select high quality and productive sites.

Study Start-Up

Working with sites that were known to ICON also had advantages in the start-up phase because we are familiar with all of the sites processes including the Ethics Committee (EC), Competent Authority (CA) as well as site contract processes.

Furthermore, experience with biosimilar products means we have acquired an excellent understanding of frequently asked questions from ECs and CAs. ICON maintains a database with queries from ECs/CAs. Accordingly the study start-up group worked to ensure the submission packages proactively addressed any potential issues. ICON also ensured when and where necessary investigators attended EC meetings. This reduced the queries from ECs, thus allowed better management of the EC/CA turnaround time.

In addition, a site activation and escalation plan was implemented to ensure site responsiveness during the start-up process, minimising unnecessary delays. Overall, this proactive start-up process ensured that enrolment went as planned.

Investigator and Patient Education, Motivation and Engagement

Investigators interested in participating in biosimilar clinical research are generally motivated by their desire to increase patient access to treatments. ICON took a proactive approach not only to educating known investigators on the benefits of biosimilar research, but also growing our database by identifying experienced clinical trial sites, but ‘new’ to biosimilar trials.

ICON’s strategy factored in the competitive environment and the prescribing environment including countries where access to the reference product was limited. This made it more attractive to investigators looking for the opportunity to provide their patients with access to a drug they may not otherwise available to them. Given that biosimilar studies generally do not have placebo arms this is also a highly motivating factor for both investigators and patients.

In addition ICON and the sponsor took a very proactive approach to investigator engagement, providing support from ICON’s internal medical team to support sites. There was a high degree of interaction from both medical and clinical teams so that these investigators were supported continually throughout the study. ICON’s FIRECREST Investigator Portal and our risk based methodology, Patient Centric Monitoring, further supported investigators to manage the trial at their sites effectively and with high quality.

Patient Recruitment Materials

ICON put in place robust site level recruitment plans to ensure that both investigators and CRAs had an understanding of what was expected in regards to patient recruitment at the beginning of the study. Patient recruitment strategies increased awareness of the trial in the medical community and ensured that sites remained focused during the trial. In addition, educating prospective patients on biosimilars and their trial journey served as a method to remove any information barriers which would inhibit patients from entering the trial. These tools included study branding, a Patient Guide to Biosimilars, Study Posters, a Study brochure, Doctor-to-patient letters as well as newsletters. In addition, the FIRECREST portal was used to improve communication between ICON, the sponsor, sites and patients,and to optimise workflow. This increased compliance at sites and supported patient recruitment and retention.

ICON successfully completed enrollment three months ahead of the contracted schedule, in spite of approximately 2 months hold on screening. This will enable expeditious submission of BLA.