The European healthcare landscape has more than a decade of in-market experience with supportive care biosimilars. However, we’re entering a new era for biosimilars in oncology with the recent launch of therapeutic biosimilars in the EU.
At the recent European Society for Medical Oncology (ESMO) Congress, held Sept. 8-12 in Madrid, the European medical industry came together for clinical data updates, expertise-sharing and advisory guidance. There were six presentations on biosimilars at the event, including those sponsored by biosimilar manufacturers. Consistent across many sessions were four core themes:
1. A unified perspective on switching from originator to biosimilar and biosimilar to biosimilar still isn’t established. Those healthcare providers who champion biosimilars as a preferred option are heavily influenced by lowered cost and are convinced of safety, but many remain skeptical of switching patients from originator therapies.
Moreover, while interchangeability, switching and automatic substitution are related, they are all different and distinct topics. ESMO has released positions on these topics in the past, notably stating that decisions on the interchangeability and substitution of medicines are the responsibility of EU member states.
Additionally, while ESMO and the American Society of Clinical Oncologists (ASCO) are cautiously supportive of encouraging drivers of biosimilar uptake, such as interchangeability, they’ve taken the position that HCPs ultimately should have decision-making power and the ability to weigh in on what treatments their patients receive. Essentially, automatic substitution should be avoided because it strips HCPs of their prescribing rights and responsibilities.
2. Extrapolation is well-established and there’s general confidence to extrapolate with little difference in attitude when it comes to therapeutics versus supportive care. The collection of real-world evidence and the experience post-launch with extrapolation is helpful but not mandatory to drive extrapolated use. Other factors such as cost and experience with prior biosimilar extrapolation may also drive adoption, especially among biosimilar champions.
3. Access improves when biosimilars are introduced since biosimilars help reduce cost, and costs are currently limiting access to healthcare. Moreover, biosimilars support the World Health Organization’s top priority: reining in the cost of medicine.
4. Patients should not be ignored. The biosimilar landscape has focused on closing HCP education gaps to ensure comfort and utilizing payers to drive uptake, but patients have a voice and there continues to be an emphasis on empowering patients to be involved in decision-making in oncology as well as immunology. Lessons learned from inflammatory bowel disease patients show that there’s a lack of knowledge of biosimilars, and with that comes concern. A 2016 study conducted by the European Federation of Crohn’s and Ulcerative Colitis Associations found that 62% of 1,181 respondents had not heard of biosimilars at all and only 12.5% thought that extrapolation was rational. Additionally, 21% were against the idea of interchangeability if they were not informed. The low awareness of biosimilars may be creating gaps in patient perceptions or misconceptions that impact their willingness to be prescribed treatment.
A continuously “trending” topic in the biosimilar landscape is around differentiation. A challenge at the forefront for biosimilars is the inability to differentiate between the safety and efficacy of one biosimilar and the originator or other biosimilars. However, manufacturing quality and reliability, as well as clinical trial design and the volume/quality of evidence to support biosimilarity, are two areas of differentiation that have been highlighted previously and were addressed at ESMO. Biosimilar manufacturers highlighted examples of process modification by originators throughout their product’s life cycle (for example, with trastuzimab and cetuximab) that lead to drift. As a result, the products can be less similar than the original batch studied clinically (and therefore support an argument that a biosimilar may actually be more similar than an originator’s later batch is to the originator in their trials).
In terms of clinical trial end points, biosimilars need the most sensitive end points that impact similarity, as opposed to merely mimicking the end points used in the trial for the reference product. Progression-free survival, a typically preferred efficacy end point in cancer, may not be feasible or sensitive enough to demonstrate biosimilarity. When you look across the trastuzumab biosimilar studies, the study end points have varied with overall response rate and pathological complete response. The FDA and European Medicines Agency prefer pathological complete response, yet preference doesn’t equate to a lack of approval, although it certainly could be a message to drive physician confidence and payer preference.
In a continued effort to support their members in the area of biosimilars, ESMO has fielded a survey with conference participants related to awareness, knowledge and experience with biosimilars. Similar to the ZS adoption survey fielded earlier this year, the survey results should yield implications that can guide further efforts by ESMO to shape opinion and appropriate use of biosimilars in therapeutic oncology. At the very least, the survey is a symbol of ESMO’s commitment to focus on this emerging new treatment category.