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The coming age of biosimilars

pharmafile | November 25, 2019 | Feature | Business Services, Manufacturing and Production, Medical Communications, Research and Development, Sales and Marketing | biosimilars, feature, pharma

With more and more biosimilars securing approval and the sheer potential value they have to offer for healthcare systems around the world, Nikhil Patel takes a look at the current market landscape and how things could be shifting for the better.

It is estimated that by 2025 biosimilars will reach a worldwide market value of over $61 billion. In the last few years alone the European Union and United States have seen increasing numbers of biosimilar applications and approvals. For example, in 2017 the European Medicines Agency (EMA) approved 13 biosimilars for seven different originator products, thereby allowing greater competition within the drug market, driving down prices for first-in-line biologic treatments and furthermore potentially improving access to innovative second- and third-line therapies. In 2018, the FDA also approved seven biosimilar medications, a number which is seemingly low but is in fact an increase over the previous year’s five biosimilar approvals.

What are biosimilars?

Biosimilar medicines are biological medical products that are an almost identical copy of an original product that is manufactured by a different company. Biological medicines are protein-based and are derived from living organisms. A biosimilar medicine can only be given approval once the ‘reference’ (or originator) medicine’s patent expires.

Biosimilar adoption

As of 2019, the NHS and other health systems across the globe have made significant strides in terms of adopting biosimilars and their cost-saving potential is widely recognised and utilised within organisations such as the National Institute for Health and Care Excellence (NICE).

It is estimated that by 2021 the NHS will be able to take advantage of over £300 million in savings through the offering of various biosimilars. As it stands today, the UK, a nation once lagging in biosimilar uptake, is now out in front with an 86-90% uptake of biosimilar versions of top-selling drugs such as rituximab (MabThera) and trastuzumab (Herceptin). The NHS is now aiming to have at least 90% of new patients prescribed the best-value biological medicine within three months of a biosimilar’s launch and at least 80% of existing patients being prescribed biosimilars within 12 months or sooner.

However, some commentators have pointed out that there is still much to do. For instance, in the EU5 (France, Germany, Italy, Spain and the UK) just 262 units of the biosimilar for AbbVie’s Humira (adalimumab) were prescribed since their launch in November 2018, compared to almost 21,000 units of the more expensive biologic, costing a total of €23.5 million. The same number of units for the biosimilar would have cost €14.5 million, meaning lost savings of nearly €10 million.

Real-world savings have, however, been successful with particular drugs; for instance, the NHS showed a cumulative cost saving of £38.8 million over two years from the introduction of infliximab and etanercept biosimilars in the treatment of rheumatoid arthritis.

In the US it is estimated by analysts that the biosimilar market will grow significantly and, by 2024, will exceed $15 billion. However, between 2019 and 2023 there will likely be a lull in activity simply due to fewer losses of exclusivity in original biologic products. By the end of 2018, of the 16 biosimilars approved in the US only three have actually been commercially launched, and there has been a very low penetration rate.

Based on a review of biosimilar launches, the Biosimilars Council found that in spite of significant price discounts and savings opportunities, barely any have been able to gain a significant market share. This is as a direct result of anti-competitive market access tactics by brand-name companies. To add to this there has been severely inadequate incentives for biosimilar use and insufficient information for patients. Taken together, this has added in the region of $2.2 billion in potential lost savings out of a total of $9.8 billion since 2015.

Credit: AAM Analysis

In order for things to improve, policy makers must take steps to ensure the viability of the biosimilar market for American patients. Without the competition that biosimilars bring, brand-name biologics will continue to drive up prescription drug spending at a rate that is unsustainable, as well as keeping life-changing treatments out of the hands of patients.

At the end of 2018, then-FDA Commissioner Scott Gottlieb repeated a warning that the agency will crack down on any delaying or prohibited tactics deployed by pharma companies to block cheaper alternative biosimilar medicines. He spoke out repeatedly against anti-competitive tactics and pricing practices and has promised to back up his words with actions.

He said in a statement: “Manufacturers are using several schemes to hamstring biosimilar competition… the net result is a lopsided playing field that disincentives biosimilar developers from making the sizeable investment in bringing such products to market.” He added that he worries pharmacy benefit managers have been “complacent participants” in the schemes. Pharmacy benefit managers are companies that control which drugs are covered and negotiate discounts on branded drugs with manufacturers. Gottlieb went onto say that, in some cases, restrictive contracting, rebating and distribution agreements may deter biosimilars from being covered and reimbursed.

This year alone has seen Johnson & Johnson engaged in legal battles with Pfizer over rebates for its biologic Remicade, while AbbVie was questioned by US Congress about how it is fending off competition for Humira. Additionally, in August, Pfizer sent a petition to the FDA accusing Amgen, Genentech and Johnson & Johnson’s Janssen Biotech of misleading physicians and patients over the issue.

Previously, in a statement while serving as FDA Commissioner, Gottlieb said: “This is just a start. We’re going to be monitoring these markets and we’ll be taking additional actions. We’re actively evaluating how we can make it easier for biosimilar manufacturers to use reference products from outside the US, where prices may be cheaper and reference products more accessible.”

The pharma industry body PhRMA has claimed reference pricing amounts to nothing more than “importing foreign price controls from countries with socialised health care systems that deny their citizens access and discourage innovation.”

Originator products such as AbbVie’s Humira, which lost its patent in November 2018, have already suffered market losses in Europe as international competition from biosimilars shaved 14.8% of total sales.

Production efficiency and education

The competition between biosimilar developers has accelerated and continues to do so as new entrants compete against each other to aggressively capture a significant slice of the market. One example is Celltrion’s Remsima (infliximab) which managed to achieve a 52% market share in Europe in the fourth quarter of 2018, marking the first time any biosimilars has surpassed the market share of the originator product. Looking at Norway alone, its health service saw an incredible 69% cost reduction with the use of infliximab biosimilar instead of originator reference Remicade, ultimately leaving the biosimilar with an 80% market share.

Though branded Remicade still holds most of the market, competition has certainly eaten away at sales as the drug brought in $5.3 billion in 2018, down from $6.3 billion and $7.0 billion in the two prior years. An assessment of Remicade biosimilars in the US is vastly different: citing prescription data for the month of May, Johnson & Johnson still hold a market share of 91% with many deeming the biosimilars to be a ‘failed market’. J&J posted $2.2 billion in Remicade sales for the first half of 2019, on pace to reach $3.2 billion for the year as a whole, indicating most of the biosimilar uptake is coming from Europe as well as the fact that Remicade has had to lower its list price by 23% in Medicare Part B since biosimilars first entered the market.

Currently, biosimilars only account for 4% of the US biologics market as compared to countries such as Japan and India which have seen penetration rates of 13% and 19% respectively. This is primarily due to a lack of education on the subject from doctors and payers who remain cautious in prescribing these new medications for use. This education deficiency is so glaring that the FDA’s Biosimilars Action Plan includes a promise to increase biosimilar education among health carers and the wider public. Just as generic drugs faced a similar symptom of slow initial uptake in the 1990s, so do biosimilars today, and given the correlation between generics and biosimilars, the primary indication is that the market will eventually explode into life.

Studies of biosimilars’ use in the clinic have emphasised further hesitation among physicians. A study published in the American Journal of Managed Care in June about gaps in oncologists’ use of biosimilars pointed out that, while global sales of biosimilars are expected to reach at least $19 billion by 2023, half of physicians have reported unfamiliarity with them and more than a third say they have never prescribed them. Furthermore, 30% of physicians in America would not prescribe a biosimilar to a treatment-naïve patient.

The future

In 2017 and 2018 alone, there were more biosimilar approvals in Europe than in the 10 years since the first ever biosimilar approval back in 2006. Though expected lulls in activity will eventually pass, both Europe and the US are set for significantly more biosimilar approvals in the coming years. The question remains as to whether or not they will have sufficient penetration rates to ultimately improve patient outcomes.

One study found that, because of the sheer amount of competition, 1.2 million patients in the US could gain access to biologic medicines by 2025. This, however, is still dependent on what will be done in the US to educate physicians and get patients behind biosimilar medications.

Nevertheless, owing to cost-savings necessary for the survival of any biosimilar or originator product, as well as prescriber familiarity, world-wide healthcare systems will not only have a greater choice of products on offer but also will be privy to truly astonishing potential savings that will enable greater patient access and what could be described as a ‘more personalised’ standard of care.