Biosimilar Infliximab Success Paves The Way For Adalimumab In Europe
Executive Summary
With the impending European launch of Humira biosimilar adalimumab in October, Scrip talks to some of those in the region that have experience in launching commercially successful biosimilars about uptake, discounts and payer attitudes.
“The next big one that comes to the market is adalimumab,” says [Napp Pharmaceutical Group Ltd.]’s director of market access and external affairs Andrew Roberts, when discussing the uptake of monoclonal antibody (MAb) biosimilars in the UK. Currently the biosimilar with the widest distribution in the UK is infliximab, with around 600,000 units distributed a year.
“The NHS policy of savings on medicines has been in place for almost a decade so manufacturers were frustrated that the NHS wasn’t doing more about biosimilars use,” says Roberts. “However, the speed at which policy moved and uptake improved was quite astonishing and over the last 18 months we’ve started to see far less barriers to uptake in the whole of the UK.” Napp distributes Celltrion Inc.’s Remsima (infliximab), Truxima (rituximab), and Herzuma (trastuzumab) in the UK.
When Remsima was first launched in Europe, an anti-biosimilar campaign by originator companies threatened to sideswipe commercialization says HoUng Kim, Celltrion’s head of strategy and operations. “They tried to cast doubt on biosimilars to influence prescribing behavior despite the totality of evidence generated to meet the requirement from stakeholders, including the European Medicines Agency,” he tells Scrip. This tactic failed to work on prescribers. According to the market research firm IQVIA, Remsima had 52% of the European market in the fourth quarter of 2017 which, according to Kim, marks the first time a biosimilar has surpassed the market share of originator drugs.
As these figures show, attitudes toward biosimilars have altered drastically in the three years since infliximab was launched onto the European market. In a biosimilars medicines commissioning framework published in September 2017, the NHS stated its aim to prescribe 90% of new patients the best value biological medicine within three months of launch of a biosimilar, and at least 80% of existing patients within 12 months, or sooner if possible. Biosimilars have the potential to deliver savings of at least £200m to £300m per year by 2020/21, official numbers state.
Since biosimilar infliximab launched in February 2015, it has saved NHS England (NHSE) £99,400,000. This figure dwarfs the savings made by prescribing generic/biosimilar versions of imatinib (£66,333,000), etanercept (£60,300,000), rituximab (£50,430,000) and voriconazole (£15,912,000).
With initial frustrations left behind, Remisima is now the most mature product in Napp’s biosimilar portfolio, and growing in use by NHSE by around 12% a year. “The UK has been a huge success story,” concurs Paul Clark, director of the biosimilars business unit at Napp. “It took a while to get there, it was a slow start but where we are now is hugely encouraging.”
According to figures from NHS England’s Regional Medicines Optimisation Committee (RMOC), by May 2018, national uptake of infliximab, in percentage of total treatment days, was 89%; while etanercept was also 89% although it came to the market a year later in April 2016, and rituximab, which came to the market in April 2017, had a 73% uptake.
Lessons Still To Be Learnt
Uptake across the UK is not a totally rosy picture for biosimilars. Because it is the decision of regional clinical commissioning groups (CCGs) within the NHS to switch from originator drugs to biosimilars, localized differences can scupper the promised savings. “There is evidence of significant and unwarranted variation between local areas and regions in the use of biosimilar medicines,” the NHS stated in its commissioning framework document. “In January 2017, one NHS Trust in central London had an uptake of infliximab of only 25%, whilst another just 16 miles down the Thames had an uptake rate of 99%.”
With biosimilar adalimumab about to hit the market, the NHS and other European payers can look to lessons learnt from tried and tested infliximab as a model for biosimilar market access success. “With infliximab we just didn’t see the right leadership locally,” recalls Roberts. The initiative has got to come from CCGs, who are the budget holders, locally, he explains. “It’s just simple project management, if you don’t see those plans laid down in advance, and everybody agreed and there are measures in place so everybody is holding each other accountable, you will not get that rapid uptake.
“The areas that did set off like a rocket for infliximab are the areas that had all those plans in place, shared accountability and were measuring what they were doing on a weekly basis. The areas that achieved 99% uptakes are those that micro-managed the change between the NHS Trust and the CCG. If you get areas where you don’t have that level of leadership and acceptance of the accountability, you won't get the uptake,” he explains. And with the NHS spending more on Humira than any other hospital drug - £333m in 2016/2017 - it needs to get the switch from the originator to biosimilar right at the first time of asking.
While infliximab is undeniably a success story for the biosimilar sector, there are still a few flies in the infliximab ointment, namely the indications where many patients could benefit but cannot access the product. Napp is hoping NHSE will further expand in its prescribing model for the MAb. “There’s been an expansion into ulcerative colitis but you haven’t seen that move into arthritis. The health service and patients could see much better long-term outcomes if they did,” says Clark. And it is no longer a matter of saving money, says Roberts, as the cost has come down by 90%. “A product that cost almost £1200 a treatment, is now costing considerably less. There is no justification for withholding treatment for a patient that needs it.” Treatment pathways, overseen by the UK’s National Institute for Health and Care Excellence (NICE), are “very restrictive” and “have not changed”, he says, which is now the main cause for frustration among both the industry and patients. (Also see " Europe Ripe For Broader Biologic Use In Inflammatory Conditions " - Scrip, 28 Oct, 2015.)
Future European Market Strategies
With Sandoz International GMBH’s Zessly approved earlier this year for use in all indications of the reference drug, the European marketplace for infliximab products is starting to look quite busy, with Samsung Bioepis Co. Ltd./Biogen Inc.’s Flixabi, Pfizer Inc.’s Inflectra and Remsima jostling for market share. (Also see "EU Biosimilar Action: New Competitors For Remicade/Herceptin, Four More Products Await CHMP OK" - Pink Sheet, 30 May, 2018.) This is healthy for a system such as the UK’s NHS that works on tendering, with the ability to choose products encouraging sustainability. While the innovator product normally retains the largest market share, the onus is on the biosimilars to disrupt the market. Biogen Inc. markets Flixabi in Europe and this is something it is hoping to do.
“I recognize that I’m third to market and that means it’s going to be a much harder and acute business situation but it’s still rewarding,” Ian Henshaw, head of biosimilars at Biogen, tells Scrip. “So, we’re going to continue to compete and we’re going to continue to work out what it takes to win.” The commercialization strategy for Flixabi is the same as for its other branded biosimilar Benepali (etanercept) says Henshaw, Europe-wide. “The first response is that we look at every single tender and contract and work out what it takes to compete in that contract, and then what it would take to win. We look at every single opportunity and as a result of that, we’re in 11 countries in Europe with Flixabi.”
While the general commercialization strategy has the same end goal in sight across Europe, the intricacies of the tendering process vary from country to country, with pricing and discounting only one part of the tender, with other considerations such as amount of product, quality of packaging and design, and necessary educational materials. “This is where the sustainability and the evolution of this marketplace is going,” says Henshaw.
Celltrion expects a certain limitation for price competition as more and more biosimilar products enter the market, HoUng Kim explains, and because of this the company is focused on a differentiation strategy for each biosimilar product it markets, planning several “value-added features”. For Remsima, “we would like to provide a more convenient and accessible treatment administration option to patients with chronic conditions so we are developing a subcutaneous version of infliximab,” he explains. Celltrion is also working to improve its production process to maximize supply efficiencies, which will, in turn, lower the price.
Blockbuster To Biosimilar
Biosimilar versions of AbbVie Inc.’s blockbuster Humira (adalimumab) will be launching into a buoyant market of converted payers and patients. Products from Amgen Inc., Boehringer Ingelheim GMBH, Sandoz International GMBH and Samsung Bioepis Co. Ltd./Biogen Inc. will all try to win market share when the doors to Europe open in October. However, AbbVie seems prepared to defend its product.
Humira Biosimilars
Amgevita and Solymbi (Amgen)
Cyltezo (Boehringer Ingelheim)
Halimatoz, Hefiya and Hyrimoz (Sandoz)
Imraldi (Samsung Bioepis and Biogen)
“Commercially, this is going to be interesting,” stated Ronny Gal in a Bernstein analyst note. AbbVie is expecting 20% decline in product sales in Europe in year one, and has the capabilities to deal with 30%. As Humira is not a hospital product, patients know if they are being prescribed a biosimilar, and AbbVie has an, unpublicized “different strategy” from that of the Remicade and Rituxan (rituximab) innovators. “In our view, AbbVie appears much more prepared than prior defenders and their key objective is to prevent the creation of large patient databases ahead of US biosimilar introduction. AbbVie is much more likely to give up price than volume,” says Gal.
Gal states that additional tactics used by AbbVie will include arguing that there's a change in formulation so that there is no proof of biosimilarity against the current version, arguing for access to new, less painful formulation through patient advocacy groups, contracting to block the biosimilar, introducing rebates for major payers, and using late-patented indications to threaten legal action, which works in conjunction with discounts.
While the price of Humira will inevitably fall, market share is not so cut and dry. “Adoption of biosimilars may be a bit slower than Enbrel,” says Gal, “but there is material animosity to AbbVie among EU payers, after what they see as price gauging. And the biosimilars are competing with each other, as well as AbbVie.”
Goldman Sachs has looked to Amgen Inc./Pfizer Inc.'s Enbrel and Janssen Pharmaceuticals Inc.'s Remicade for pricing guidance but note two meaningful differences between them and Humira. Firstly, Humira has a dominant and growing market share outside the US, in terms of sales, heading into biosimilar competition, while both Enbrel and Remicade were losing share at the same point; although this could be offset by the fact that Humira is expected to see three to four biosimilars in the first year, while Enbrel and Remicade saw only one or two.
“Our Humira decline curve is steeper in the first year with -18% growth while Enbrel was down 8% and Remicade down 10%. Over the three years post biosimilar competition, our Humira decline is a cumulative 32%, which is less aggressive than what we expect for Enbrel (-37%) and Remicade (-48%); we do not expect Humira’s long-term OUS erosion to be as steep due to the drug’s best-in-class profile and strong, growing market share even before any anti-TNF biosimilars were on the market,” it stated in an equity research note.