BIOLOGICAL drugs are the new darlings of medicine. In recent years, they have doubled treatment rates for several , and . But these medicines, which are large, complex molecules produced by living cells, carry hefty price tags, and now comprise eight of the world’s .
A one-year course of the biological breast cancer drug trastuzumab (sold as Herceptin), for example, costs $50,000. In the UK, biologics have contributed to a .
“Some doctors are worried these cheaper copies won’t work as well or as safely. Are these fears justified?”
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That’s why, starting this year, the NHS to substitute all brand-name biologics for cheaper generic versions, hoping to cut costs by up to 70 per cent.
Some doctors are worried these cheaper copies won’t work as well or as safely, saying that competing firms won’t be able to perfectly replicate complex biologics. Are these fears justified or simply big pharma scaremongering?
Because biologics are made by cells, they are tricky to copy. Trastuzumab, for instance, is a multichained protein secreted by . Different cell batches and even temperature and light can subtly alter the product.
So unlike chemical drugs such as aspirin, generic biologics, termed biosimilars, aren’t exact copies. “Whereas aspirin is like a bicycle – it doesn’t have many parts and is easy to copy – a biological drug is more like a jetplane,” says Gregory Moore at Monash Medical Centre in Melbourne.
But that hasn’t stopped firms developing biosimilars as patents for the first wave of blockbuster biologics expire. Biosimilar versions of the arthritis drugs infliximab, etanercept and rituximab became available in the UK in 2015, 2016 and 2017 respectively. Biosimilar versions of trastuzumab and bevacizumab – another cancer medicine – were approved by the US Food and Drug Administration (FDA) in the past four months, and many more are in the pipeline.
However, uptake has been patchy. show that in some UK regions only 10 per cent of patients are being switched to infliximab biosimilars, compared with 100 per cent in others. In the US, biosimilars have captured just 7 per cent of the infliximab market, while in Australia they have grabbed a mere .
Clearly, there is a need for change. Norway introduced a similar policy to the NHS’s plan, and has seen a big impact. Since 2014, the country has required all patients who are newly prescribed infliximab to be given the cheapest biosimilar available.
Companies compete to win an annual tender to supply the drug, which has seen the drug price drop by from about $2500 per dose. A randomised, double-blind controlled trial funded by the government found when 482 patients with arthritis, Crohn’s disease and other inflammatory conditions were maintained on brand-name infliximab or switched to a biosimilar for one year.
Other Nordic countries have also enthusiastically adopted generic biologics. Infliximab biosimilars now make up 96 per cent of the market share in Denmark, 88 per cent in Finland and 34 per cent in Sweden.
There have been no significant problems with the swap. In Denmark, where a nationwide registry was set up to monitor all patients switched to biosimilar infliximab, in their disease was observed after a year.
Safe to swap?
However, doctors in other countries remain wary. A found that only 45 per cent of 1200 surveyed US physicians thought biosimilars were safe and appropriate to prescribe.
Patients are also uncertain. A of more than 3000 people in the US, UK, France, Spain, Germany and Italy found that the vast majority of the general public had never heard of biological drugs or biosimilars. Of those being treated with biologics, only 10 per cent were aware of biosimilars, and less than half of those said they would feel comfortable with switching, fearing their safety and efficacy.
But why? Lack of evidence doesn’t seem to be the issue. Regulators like the FDA and European Medicines Agency require manufacturers to prove their products are just as effective and safe before they can be sold. This includes running a that compares the biosimilar with the brand-name product. Dozens of trials have confirmed that they are as good as the originals. So why are some doctors so reluctant to use them?
, departing CEO of Australia’s Generic and Biosimilar Medicines Association, which represents manufacturers, puts it down to two factors: brand loyalty and big pharma fearmongering. “The fact that these are called ‘similar’ means that originators can say, ‘Hey doctor, they’re not quite the same, maybe you should be a bit worried’,” she says.
Companies with patents on the original biologics appear to be heavily investing in shoring up brand support. For example, drug firm AbbVie made , including speaking and consulting fees, to more than 27,000 US doctors between 2013 and 2015 related to its biological arthritis drug adalimumab. This is currently the , but biosimilar competitors are due in October.
Influential doctors are a prime target. For instance, AbbVie paid more than to at the University of Texas, who last year gave a talk on biosimilars at the annual meeting of the American College of Rheumatology, titled “The data is not convincing”. Fleischmann confirmed he had received payments from AbbVie, but declined to discuss their amount or purpose with 91av.
In the US, insurers are also limiting access to biosimilars. For example, don’t cover infliximab biosimilars. In September, Pfizer, which makes one of these biosimilars, sued originator company Johnson & Johnson for allegedly arranging “” deals with insurers.
“Only 45 per cent of 1200 surveyed US physicians thought biosimilars were safe to prescribe”
“Things get nasty,” says Wood. “We’re talking about big-dollar products here, so companies have a heck of a lot to lose.”
Then again, Moore says doctors have legitimate concerns about biosimilars. One is that they only need to be shown to be equivalent to the originator drug for one condition, say rheumatoid arthritis, to gain regulatory approval. That means they can be used to treat another condition, like inflammatory bowel disease, without needing further trials.
Moreover, because biologics usually target the immune system, slightly different versions could potentially cause severe allergic reactions in some patients, says Moore. That is why his hospital, where he is head of inflammatory bowel disease, has a policy of not prescribing biosimilars, he says.
AbbVie pays to Moore and is a major financial supporter of , but Moore says patient safety, not brand loyalty, is his concern. “When the originator drug has kept your patient well for years, and a new player comes to market that doesn’t have quite the same robustness, that’s going to play on your mind.”
Fleischmann says he has the same mindset. “It may be fine to switch patients to biosimilars, but what if it isn’t? We don’t have enough evidence yet.”
On the other hand, , a clinical pharmacologist at the Centre for Evidence-Based Medicine at the University of Oxford, says the same concerns should apply to brand-name biologics. “The great difficulty for all biological drugs, originators included, is that manufacturing variability means that each batch is slightly different,” he says.
For this reason, he would like to see better monitoring of both originators and biosimilars after they enter the market.
At the moment, the UK Medicines and Healthcare products Regulatory Agency . Biosimilar manufacturers are also required to monitor small groups of patients after they start using the drugs. But Aronson believes a nationwide registry that monitors all patients taking biologics would be helpful, so that any dodgy batches could quickly be identified and pulled.
Clearly, biosimilars must be evaluated properly before and after they enter the market, but so far it seems there is no real reason to fear them. With the NHS strapped for cash, switching to cheaper drugs seems an obvious move. Patients don’t care who makes their drugs – they just want them to work.
This article appeared in print under the headline “The imitation game”
