Regulatory shift could alter biosimilars business case

The evolution of US and EU regulators’ policy around clinical efficacy studies (CES) was a focal point of discussion at the recent Festival of Biologics 2025 we attended in Basel, Switzerland.

At the event, data was presented that suggests that a regulatory shift on CES by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) could not only present significant commercial opportunities for biosimilar developers and the pharmaceutical manufacturers they often collaborate with, but for healthcare providers and patients globally, who currently often lack access to these vital medicines.

Read more on biosimilars policy and regulation.

• EMA biosimilars policy shifts over clinical efficacy studies
• Action required to address growing risk of ‘biosimilars void’
• Why comparative efficacy trials for biosimilars must go
• EMA endorses biosimilars switching

Biosimilars provide competition to originator biologics, which are drugs that contain active substances derived from biological sources, such as mammalian cells, and are often large, complex molecules with an inherent small degree of heterogeneity. Unlike small molecule generic medicines where the active ingredient is chemically identical to the originator drug, biosimilars, while highly similar to the originator biologics, are never completely identical to those biologics they are developed with reference to.

This scientific reality has had a bearing on the regulatory hurdles biosimilar developers need to clear to obtain marketing authorisation.

While regulatory data used in the development of originator biologics can help inform the development of biosimilars, biosimilar developers must evidence ‘biosimilarity’ with the originator product to regulators. In practice, regulators have typically required that comprehensive scientific CES be carried out to meet this requirement. This entails conducting expensive and time-consuming ‘phase three’ clinical trials with patients.

Things began to change in 2021 when UK regulator the Medicines and Healthcare Regulatory Authority (MHRA) updated its guidance to recognise that conducting CES will not always be necessary if there are other sound scientific ways of demonstrating biosimilarity. That move allows biosimilar manufacturers to rely more heavily on comparative analytical and functional data, as well as what is known from clinical experience and quality attributes of the originator biologics product, to meet their regulatory requirements.

The change in approach by the MHRA was not replicated immediately by other prominent regulators, however – both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) continued to insist on data from CES being evidenced to support claims of biosimilarity. This has come at a cost to industry – and patients – as was explained to delegates at the Festival of Biologics 2025.

According to data presented at the event, CES account for at least 70% of clinical development costs for biosimilars. Running with such significant added costs has impacted on the number of biosimilars being developed to compete with biologics – even though the main product patents applicable to many of the ‘first wave’ biologics developed in the 2000s and early 2010s, which currently provide market exclusivity for the companies behind those products, are due to expire over the next few years.

According to the FDA, for example, there are 118 biologics due to move off-patent over the next decade, representing a $232 billion opportunity for biosimilar rivals. However, there are just 12 biosimilars under development earmarked to compete with those originator biologics. The EMA said that 70% of biologics face no biosimilar competition at all. This differential between the number of biologics due to move off-patent and the lack of biosimilar competition for the originator products is known as the ‘biosimilar void’.

There are signs that this situation can change, however.

As Pinsent Masons reported, in April the EMA opened a consultation on the contents of a draft ‘reflection’ paper in which it said that biosimilar manufacturers may not always need to undertake CES to obtain marketing authorisation for their products.

The EMA has backed “a tailored approach” to demonstrating biosimilarity, stating that CES may not be necessary for “biosimilars that can be thoroughly characterised and have shown high similarity on an analytical and in vitro pharmacology level”. At the time, it added: “Comparative clinical pharmacokinetic studies are still essential elements in biosimilar development but some adjustments to the data requirements, such as inclusion of immunogenicity parameters and/or modifying the study design (e.g., one-dose vs multiple-dose), could be considered.”

The EMA’s consultation on its paper closed on 30 September. While reflection papers do not constitute formal EMA guidance, the regulator can use them to provide clarifications on evolving issues and to invite comment from stakeholders on specific issues. A finalised reflection paper is expected to be published in the coming months.

At the same time as the EMA policy on CES evolves, there has been an example of the FDA’s own approach changing too.

In July, biosimilar developer Formycon announced it had stopped recruiting patients for a ‘phase three’ clinical trial in relation to a biosimilar it is developing to compete with the blockbuster cancer drug Keytruda, its pembrolizumab biosimilar FYB206, after receiving positive feedback from the FDA on its plans to “demonstrate the therapeutic comparability of [pembrolizumab biosimilar FYB206] with …Keytrudabased on comprehensive analytical data and data from the [pharmacokinetic] study” it had run in Europe.

The company said at the time: “Based on our stringent [pharmacokinetic] study design, our sound scientific rationale and the comprehensive analytical data showing high structural and functional comparability with the reference drug, we have aligned with the FDA on a streamlined clinical development program that allows us to skip the Phase III trial. This approach accelerates development without compromising on quality, safety and efficacy. Furthermore – the streamlined clinical program supports our strategy to provide the pembrolizumab biosimilar FYB206 to patients worldwide as soon as possible and thus improve access to this essential drug.”

The case indicates a willingness on the part of the FDA to relax requirements around CES studies where other data supports this. However, what biosimilar developers need now – from the FDA and EMA – is a firming up of policy around alternatives to CES in the form of concrete guidance they can rely on. This should be a major focus of industry lobbying efforts over the months ahead.

A clear regulatory shift could help cut the time it takes to obtain marketing authorisation for biosimilars and, as the figures above show, in turn slash the costs involved in bringing those products to market. This could have a profound impact on the biosimilar void in mature markets like the US and Europe, because it could dramatically alter the business case for investing in certain biosimilar candidates – even those that developers have previously considered would not be commercially viable.

The opportunities do not end there, though.

Currently, biosimilars – and biologics, more generally – make up just a small fraction of the total number of pharmaceutical products available in emerging markets. There are a number of reasons for this, but a major factor is the lower price that developers can expect to achieve when selling into emerging markets like south-east Asia, Latin America and Africa compared to in the US and Europe, which makes off-setting development costs difficult.

A shift in regulatory policy on CES by the FDA and EMA, however, could move the dial. This is because medicines regulators in emerging markets often take their lead on regulatory matters from the FDA and EMA, meaning they would be likely to mirror any approach those regulators formally adopt to relaxing the requirements biosimilar developers face around CES. This would make it cheaper to produce and sell biosimilars in those emerging markets.

One prominent speaker at the Festival of Biologics2025, Dr Paul Cornes, from the European Society for Medical Oncology, is of the view that enabling biosimilars to infiltrate more markets globally can be a trigger for the elimination of deaths from cancer globally within the next few decades – in what would surely represent one of the most significant medical milestones ever achieved.

Whether it is in addressing the biosimilar void in markets where biologics are already prevalent, or infiltrating emerging markets where they are rare, there are other challenges biosimilar developers face in increasing the adoption of their products.

Medical practitioners often need persuading to switch away from prescribing originator biologics where cheaper biosimilars are available. This is largely because the implications of switching are not always well understood, leading to concerns around clinical outcomes and patient trust. Industry has an important role to play in educating doctors, pharmacists and payers, as well as patients, over the genuine equivalence biosimilars offer in comparison to biologics – in terms of both their safety and efficacy.

The challenge for industry is to achieve this education piece without flouting strict marketing rules.

In the UK alone, there have been various cases that have made clear that promotional material and activities should be kept separate to educational activities. Industry events, for example, designed to educate stakeholders on the benefits of biosimilar switching, should not become a platform for promoting particular biosimilar products. The same principle applies to the use of advisory boards, to email exchanges with medical practitioners, to public presentations, the issuing of press releases, and publishing on social media.

What is clear from the Festival of Biologics 2025 is that there is increasing optimism about the regulatory environment biosimilars developers will be operating in over the years to come. Given these positive indications, biosimilar developers – and other pharmaceutical companies that often play a crucial role in investing in biosimilar development and enabling manufacturing at scale – should reevaluate their biosimilar candidate list to see whether the business case for investing in those potential products is now made.

Co-written by Kiah York of Pinsent Masons.