The first biosimilar was launched in 2006, but it is only now that the explosion of biosimilars into the market seems guaranteed. With the imminent or recent patent expiry of a range of biologics in oncology, rheumatoid arthritis and diabetes the scene is set for a dynamic influx of biosimilars that promise patients and healthcare systems effective treatment for a fraction of the cost of the biologic they will replace.
It is a market projected to grow by ~35% up to 2025 to a global value of $61.47 billion. Currently the market is driven by 4 key players: Sandoz, Mylan, Amgen, and Pfizer, capturing 75% (12/16) of total 2018 EU approvals.
Biologics vs biosimiliars
Biologics are drugs that mimic or block natural chemicals in your body. Biosimilars, as the name suggest, are similar but not the same. Unlike generics, biosimilars are not exact copies of expired medications, but differ in structure in non-important, non-clinical portions of the molecule. Most often they are developed through reverse engineering of the original biologic to develop a biological entity that has a similar structure and function. The European Medicines Agency (EMA) defines a biosimilar as ‘a biological medicine highly similar to another biological medicine already approved in the EU (reference medicine) in terms of structure, biological activity and efficacy, safety and immunogenicity profile’. This means that biosimilars are permitted to have small structural differences from the original licensed reference product but this must not alter how well the drug works, how safe it is, or how the drug reacts with the body’s immune system, and this is determined through rigorous comparability testing.
Challenges with biosimilars
Approval for biosimilars is rigorous, achieved with a step-wise process with a reduced dossier. The development programme explores: quality, non-clinical effects and a clinical impact through a programme of Phase 1 PK/PD studies, Phase III equivalence studies against the reference biologic product, safety demonstrations, immunogenicity assessments and risk management plans.
Unsurprisingly, manufacturers of biologics reiterate that biosimilars cannot be declared as interchangeable. However, the EMA has declared biosimilars safe and interchangeable with the original biologics they mimic, a position that is supported by the National Institute for Health and Clinical Excellence (NICE) in the UK. In response, biologic manufacturers have undertaken an extensive programme of price cutting in order to improve competitiveness.
Humira as a case study
The patent for Humira (adalimumab), once the world’s biggest selling medicine, expired in October 2018 and biosimilars from Amgen, Sandoz, Fujifilm Kyowa Kirin Biologics and Biogen are waiting in the wings to topple Humira’s crown. Not surprisingly, the winners for biosimilars will be centralised healthcare systems, like the NHS in the UK, who can drive a switch to cheaper biosimilar products and secure cost savings. Indeed, in November 2018, the NHS England announced it would expect to save £300m of drug spend by securing deals with Humira biosimilar manufacturers, and has issued guidance to NHS Trusts to initiate 90% of new patients onto ‘best-value’ medicines within 3 months of a Humira biosimilar launch and switch at least 80% of existing patients to the best value biologic (be that Humira or biosimilar) within 12 months.
So, whilst manufacturers may not consider biologics and biosimilars to be interchangeable it is clear that healthcare providers and indeed patients probably do.
While the European loss of exclusivity for Humira occurred in 2018, the full impact of this event will be realised in 2019 and promises to be exciting. Of course, the EU experience provides a rehearsal for the US market where Humira is due to lose exclusivity in 2023 – watch this space.
Uptake of biosimilars
So…if biosimilars are as effective as biologics, tested with comparable rigour and considerably cheaper than biologics why are they not prescribed to all patients?
The problem with biosimilars is often uptake, which may be low for a variety of reasons including variances in country-specific polices relating to biosimilars and patient or clinician knowledge and willingness to embrace biosimilars. Switch programmes are therefore vital for both healthcare professionals (HCPs) and patients and these must be supported by effective education and, of course, positive data from studies and real-world environments. Further, a long-term, multi-stakeholder framework that supports biosimilars is required to inform, maybe even enforce, increased uptake. In this regard initiatives that bring together HCPs, professional clinical groups, patients and patient groups, as well as Government bodies and industry are essential.
Biosimilars in the UK – the future
With one eye on Europe, of course, one cannot forget the UK and its imminent departure from the EU family. Currently, marketing authorisation holders for biologics and biosimilars largely reside in the UK. For products to be used in the EU, post-Brexit marketing authorisation holders will need to reside in the EU. Could this mean biosimilar registrations leaving the UK with research and development likely to follow?
The UK’s Medicines and Healthcare products Regulatory Agency (MHRA) have stated they will grant all EU registered biosimilars UK marketing authorisations on the day of the UK’s exit. Similarly, they have outlined they will review any application for a product receiving a positive opinion from the European Medicine Committee for Medicinal Products for Human Use (CHMP) within 67 days. So, what are the downsides? Biosimilars in the UK will have to reference UK licensed biologics and reliance on data from EU licensed reference biologic products that are not licensed in the UK will not be permitted – if this makes the UK a less attractive market for biosimilars remains to be seen.
We live in interesting times, and the march towards biosimilars with promises for patients, HCPs and healthcare systems seem assured.