This study reviewed the changes in utilisation, spending and adoption rate of the monoclonal antibody biosimilars associated with the various value-driven healthcare strategies implemented. It also analysed the price difference between five biosimilars (i.e. infliximab, adalimumab, trastuzumab, rituximab and bevacizumab) and their RBPs, and quantified the cost savings from uptake and use of these biosimilars in the public healthcare sector. Following subsidy listing, the utilisation of most biosimilars increased steeply, with the adoption rate reaching up to 95% within 1 year of listing. A significant decline in spending was also observed due to the substantially lower prices of biosimilars. To date, it is estimated that approximately $136 million in cumulative cost savings have been achieved over the past 5 years.

Singapore’s success in its high adoption rate of biosimilars hinges on a multi-pronged approach, similar to what is practiced in the United States (US) and several European countries [16,17,18,19]. In addition, Singapore’s efficient healthcare system, geographical advantage, and synergies in supply chain within public healthcare facilitated swift biosimilar adoption. One key strategy commonly reported in the published literature to encourage support for value-driven healthcare is improving stakeholder engagement, especially with the healthcare professionals. According to recently published reviews [4, 20, 21], despite a positive attitude towards prescribing biosimilars, most healthcare professionals still have reservations around interchangeability, switching and regulatory issues. Early clinician engagement during the ACE’s evaluation of the first monoclonal antibody biosimilar revealed that clinicians support starting biosimilars in new patients, but will only consider switching among stable patients if affordability is a concern. Noting this feedback, the ACE further engaged clinicians from gastroenterology, rheumatology and dermatology departments across Singapore’s public healthcare institutions to encourage changes in their prescribing practice for infliximab. This was achieved by providing more information on the clinical evidence for biosimilars, including switching, and highlighting the MOH DAC’s considerations in recommending biosimilars for subsidies. Besides partnering with healthcare professionals, the ACE also sought support from other stakeholders through meeting platforms with MOH senior management, Chairmen of medical boards from public healthcare institutions, and the HSA to share current evidence for biosimilars, their potential to improve patient access to treatment, and the associated cost savings to the healthcare system from their use. Although slower uptake was observed for infliximab, subsequent biosimilars listed between 2020 and 2022 generally experienced swift adoption in Singapore’s public healthcare institutions. In Denmark [16] and Sweden [17], where extensive stakeholder engagement was implemented, optimal biosimilar adoption was observed for trastuzumab, which achieved 80% share within 1 year for Sweden and more than 95% share within 6 months in Denmark [16, 22]. In contrast, published data from countries such as Korea [23], the US [24] and some European countries [22] demonstrated that biosimilar use remains to be optimised.

A second value-driven healthcare strategy involves disinvestment from non-cost-effective drugs and encouraging the use of lower cost alternatives. During the evaluation of infliximab, the ACE assessed the biosimilar brand to be clinically comparable with the RBP and more cost-effective [25]. In turn, the MOH DAC recommended delisting the infliximab RBP, with a 9-month transition period, post biosimilar listing. Relisting of the RBP will not be considered within a 3-year period to encourage companies to submit the best pricing proposal. In addition, public healthcare institutions are given early notifications about delisting of the infliximab RBP and biosimilar listing to allow sufficient time for downstream stock supply and inventory management. This also gave clinicians more time to assess patients for potential switching (to biosimilar or alternative subsidised treatments), and to offer financial counselling as needed. Resources including clinician and patient education materials were developed to facilitate discussions between doctors and patients and enable informed decision making by patients. To further nudge prescribing behaviours, prompts were also built into clinical prescribing systems to alert prescribers on the available lower cost biosimilar alternative and provide reference to the published drug guidances.

The ACE employs various pricing strategies in alignment with the 2020 WHO guideline on country pharmaceutical pricing policies [26]. VBP negotiations leveraging brand-specific subsidy listing encourages price competitions, and internal reference pricing applied helps to ensure that prices of comparable treatments are set at the same or a similar level. External reference pricing is also used informally as a tool to ensure biosimilars are fairly priced relative to overseas countries. To date, these strategies have worked well to achieve substantial price reductions for biosimilars upon first listing. Notably, mandatory price reduction of biosimilars or RBPs ranging from 15 to 80% upon biosimilar entry have been implemented in other countries such as Korea [23], Japan [27], Australia [28] and several European Union (EU) countries[29]. Despite being a small country with no mandatory price reduction measures, Singapore has achieved substantial price differences of up to 80% between RBPs and biosimilars. Lastly, to ensure that savings obtained through price negotiations translate to reduced patient expenses, public healthcare institutions are required to adhere to a recommended MSP for subsidised drugs.

After the implementation of subsidies for biosimilars, a critical next step for driving biosimilar adoption is to closely review utilisation trends, to identify early signals of low adoption and devise interventions to improve adoption in public healthcare institutions through the National Pharmacy and Therapeutics (NPT) Committee. The committee comprised representatives from the public healthcare institutions with an aim to encourage the use of cost-effective medicines, including generics and biosimilars. To further drive biosimilar uptake, the pay-for-performance (P4P) framework offers financial incentives to public healthcare institutions when a set target of biosimilar adoption is met, similar to the practice in the UK where biosimilar use is regularly tracked as part of the national indicators [30]. For example, trastuzumab was monitored under the P4P framework, starting in 2021. Despite the implementation of a multi-stakeholder approach and early notification of the subsidy listing for trastuzumab, there was suboptimal uptake of biosimilars and an increase in the use of subcutaneous trastuzumab RBPs during the coronavirus disease 2019 (COVID-19) pandemic. Subcutaneous trastuzumab was preferred due to the ease of administration and avoidance of hospital visits when hospital resources need to be optimised. After reviewing the first 3 months of utilisation data post-subsidy listing, the ACE shared the findings with key clinicians across public healthcare institutions to understand potential challenges faced and to offer support for higher adoption. Through continuous monitoring and stakeholder engagement, trastuzumab biosimilars saw an increase in further uptake, achieving 72% share after 2 years of listing. This demonstrated the importance of active utilisation review with stakeholder engagement to improve biosimilar adoption. In contrast, countries with suboptimal biosimilar adoption such as Korea reported a lack of policies such as monitoring prescription patterns and prescribing guidelines to enhance biosimilar uptake [30].

There are a number of limitations for this study that may influence interpretation of the findings. First, we conducted the analysis from the public healthcare system perspective, where subsidies for the listed drugs were applicable and are expected to impact prescribing practice. In contrast, levers to nudge prescribing behaviours, including subsidies and VBP prices, are not extended to the private sector, thus the biosimilar adoption rates could be different from those observed in the public sector. Prescribing data in the private sector was also not available. Potential market implications to the private sector from post-subsidy listing of biosimilars could not be ascertained and is not within the scope of the study. Nonetheless, the private sector only serves a minority (approximately 20%) of the total population of Singapore in the acute care setting [3]. Second, the estimated numbers of patients who benefited from the biosimilar treatments were derived based on the doses used for the main indication, and unit prices used to compute cost savings do not account for additional rebates from manufacturers, which may potentially lead to over- or underestimation.

Third, the observation periods were relatively short for biosimilars listed between 2021 and 2022, whereas continued monitoring would be required to assess long-term trends. Next, comparison of drugs based on therapeutic areas and approved indications was not conducted due to factors such as the wide range of different indications used, different available formulations (intravenous vs. subcutaneous), and the emergence of new therapies in the therapeutic areas, all of which could affect their utilisation to varying extents. A descriptive approach was instead undertaken, which made it difficult to draw definitive conclusions without control groups or randomisation. Further investigation using longer-term and patient-level data would be required to conclude the relationship between healthcare strategies, utilisation, and cost savings attained from both healthcare system and patients’ perspectives.