The rise of 'biosimilars'

Female scientist holding a test tube which had purple liquid in it.

Biological therapies have become increasingly used for the treatment of inflammatory conditions. The most well-known of the biological therapies are probably the TNF-α inhibitors, pioneered at the Versus Arthritis funded Kennedy Institute in the 1990s.

How do anti-TNF drugs work?

Essentially, anti-TNF drugs provide a blockade that halts the cycle of inflammation, a hallmark of rheumatoid arthritis. Unfortunately, anti-TNF therapy doesn’t work for everyone. Around 40% of patients who are prescribed these drugs either cannot tolerate or don’t respond to this type of treatment. It’s still unclear why some people respond to anti-TNF and some do not. Doctors are unable to tell before starting treatment whether it will work, so the current method of prescribing is trial and error – when one therapy fails, another is tried.

In order to avoid putting people on expensive medications which may not work, researchers are looking for clues to predict who will or will not benefit. Studies have been conducted investigating a number of genes and proteins, as well as metabolites (products of reactions that take place within the body) present in urine, and even brain activity. This area of research is in the early stages, but some of these have shown real promise and may eventually allow doctors to tailor treatment to the individual patient.

How are drugs researched and developed?

As more becomes known about the inflammatory pathways and messengers involved in individual conditions, researchers have been able to use drugs, targeting different components of the inflammatory process.

Biological therapies are expensive compared to conventional drugs (such as methotrexate), so the costs of these can mount up quickly. In the UK, biologics are only prescribed to patients with an active moderate to severe condition where conventional therapies have previously been unsuccessful. Cost reduction, with a view to improving access to biological therapies, is therefore an important focus of ongoing research.

When a new drug is discovered, it’s usually patent protected, which gives the patent holding company exclusive marketing rights of that drug for the life of the patent. This helps them to offset the enormous costs incurred during the research and development process. Drug patents usually only cover a period of 20 years, meaning patents for original biological therapies will expire within a given time. This will allow other drug companies to manufacture ‘biosimilars’.

What are biosimilar drugs?

A biosimilar drug is defined by the World Health Organisation as one that is similar in terms of quality, safety and efficacy to an original, licensed product.

Biosimilars are permitted to have small, structural differences from the original but these mustn’t alter the ‘how well’ the drug works, how safe it is or how the drug reacts with the body’s immune system. For conventional drugs, this is relatively simple but for proteins such as antibodies or receptors, it becomes more challenging.

Biosimilars are regulated in the same way as the original biological therapies, by the European Medicines Agency (EMA), with the added condition that drug companies must prove that the structure of their drug is similar to the original, before clinical trials for equivalence can begin. This requires laboratory testing: using specialist equipment to examine the sequence of parts which make up the antibody.

Results of these experiments for the new biosimilar are then compared to those from the original drug. By definition, biosimilars cannot perform markedly better or worse than their respective ‘bio-originals’, as any differences in biological activity or safety would constitute a novel product.

The future...

Biological therapies have come a long way in the last 20 years, and the situation looks even brighter for the future. Research is leading us towards better performing, safer, more specific drugs as well as ways to ensure patients receive the best drug for them. The reduced costs of biosimilars also have huge potential for improving access to biological therapies in years to come.