Most companies prioritise launching innovative therapies in high-income countries due to their greater ability and willingness to pay. This greater funding opportunity allows for earlier adoption of innovative, high-value products, which help to fulfil commercial expectations and realise returns on their research and development investment. As a result, these high-income markets have grown habituated to assessing innovative therapies with a variety of evidence profiles through increasingly sophisticated health technology assessment (HTA) capabilities. The evaluations performed by these HTA institutions often set a value perception standard for a given therapy for the rest of the world once the product expands its regulatory footprint to low and middle income countries (LMICs). Hence, markets where launches are delayed due to a decreased ability to pay are increasingly reliant on the opinions of authorities in these earlier-launch markets. It is common for authorities in LMICs to reference marketing authorisation decisions, funding decisions, and real-world experience in the earlier-launch markets when making their local decisions.
However, this trend may not hold true for biosimilars, where these LMICs may be prioritised for launch of these lower-cost options. Biosimilars create a new paradigm of competition for previously unrivaled branded biologics – innovative breakthroughs that are traditionally beyond the LMIC affordability range. Unlike their small-molecule generic cousins, biosimilars carry inherent safety risks due to different manufacturing processes. Such bioequivalence differences and their clinical risks would complicate LMICs’ ability to capitalise on the economic advantages of biosimilars. However, the WHO prequalification (WHO-PQ) programme is likely to help these LMICs to overcome these challenges.
The WHO-PQ programme was originally developed to facilitate the evaluation of innovative products, such as vaccines, medicines, and medical devices, in countries that either lack well-developed regulatory authorities or the infrastructure required to evaluate these products. It offers an independent, science-based certification of medical products that meet the international standards for safety, quality, and efficacy. The intent is that the confidence instilled by the certification can help support local marketing authorisation and clinician adoption of these products by under-resourced countries. To date this programme has certified more than 500 small molecule therapies and vaccines, which mostly address diseases disproportionately affecting LMICs, such as malaria and HIV. Despite biosimilars being available in Europe via the EMA since 2006, and in the USA since 2015, the WHO-PQ programme had not conducted an assessment for the prequalification of biosimilars as of the end of 2016.
However, in early 2017, the WHO announced a potential game-changer for biosimilar adoption in LMICs – the launch of a pilot initiative for the prequalification of oncologic biosimilars. The confidence instilled by biosimilar WHO-PQ will likely expedite biosimilar marketing authorisation, a major hurdle to patient access to these clinically vital and economically relevant treatment options in LMICs. Thus far, the pilot programme only includes rituximab, used primarily in non-Hodgkin’s lymphoma and chronic lymphocytic leukemia, and trastuzumab, used primarily in breast cancer. However, if the WHO’s biosimilar endeavour is successful, it will likely extend to more oncology biologics, if not other specialty areas. Moreover, in combination with this pilot programme, the WHO aims to take additional steps to support the introduction of the prequalified medicines into LMICs by publishing case studies of how other countries have successfully incorporated biosimilars within medical practice and supporting the education of prescribers and patients on the benefits of these medicines. In addition, they will allow local regulatory institutions to participate in the WHO-PQ programme which will further disseminate best practices across institutions, while fostering local capabilities to assess complex therapies. The provision of biosimilar approvals based on inclusion within the WHO-PQ list of medicines will also bolster any existing legislation regarding regulation and possibly funding of oncologic biosimilars.
FIGURE 1. Economic Evolution of LMICs and Biosimilar Registration Progress
It is important to note that some LMICs already have experience approving biosimilars and have started developing legislation relating to the regulatory approval process for these products (FIGURE 1). For instance, both MEX and COL have biosimilar versions of four major biologic brands (NEUPOGEN™ (filgrastim), $AMGN; REMICADE™ (infliximab), $MRK; and, NEULASTA™ (PEG-filgrastim), $AMGN)), while COL also has a biosimilar for ENBREL™ (etanercept, $PFE). In fact, biosimilar regulatory approval in LMICs can race far ahead of most established regulatory agencies like the FDA and EMA. LMIC countries that are on the cusp of pushing out of the LMIC territory and into the ‘high income’ stratum are less likely to benefit from the WHO-PQ programme. As they continue to evolve into higher economic development levels, they will be obligated to implement policy updates to match other countries in the high income strata. Instead, it is more likely that the greatest benefit from the WHO-PQ programme will be countries even less developed. Therefore the question of whether a hard-and-fast rule that all LMICs would be allowed to leverage the WHO-PQ programme is an important one to address by the WHO and local regulators. Perhaps LMICs will need to be selected based on their regulatory capacity to address bioequivalence as well as their existing history of biosimilar approval history in order to qualify for the WHO’s programme.
Biologic brand originators may have a credible argument whilst critiquing these policy imperfections of the WHO-PQ. Apart from shortening the exclusivity timeline for these brands, the certifications may also open the door for regional procurement. Historically the lack of uniformity across regulatory decisions by local institutions has created barriers to centralise procurement through regional tenders. However, the WHO-PQ certification could open a pathway for institutions like Latin America’s PAHO (Pan-American Health Organisation) and the Middle East’s GCC (Gulf Cooperation Council) to overcome local country differences in regulatory evaluation, and organise multi-market procurement to further reduce prices.
For biosimilar manufacturers, the situation is less straightforward. They would obviously benefit from expedited commercialisation timelines. Additionally, with the certification, regional procurement could be possible, and volume would also likely increase due to procurement eligibility by the United Nations for even broader distribution than PAHO or the GCC could establish. Such super-national tendering would lead to less commercial appeal due to price decreases. To counterweight this, the avoidance of local country registration within these regions could introduce savings to the launch process. However, it is critical for the commercial appeal of launching biosimilars to remain such that established companies with strong biologic manufacturing capabilities continue to bring these important treatment options to the market. If the commercial opportunity reduces to the point that these well-reputed companies cease biosimilar development, the prospect of safe, effective, bioequivalents at a lower cost may be endangered.