As I was running out the door of the 2017 CBI Biosimilars Summit last year, I stopped and introduced myself to Eric Sjogren, former director of strategic business intelligence for Merck. Sjogren had just finished the final presentation of the conference, which turned into a conversation with attendees about predictions for the biosimilar industry in 2017. Little did we both know, eight months later, we’d be signing a contract to become co-presenters at the 2018 CBI Biosimilars Summit this past January. We opened the conference by revealing whether our 2017 biosimilar predictions had come true and how we expected them to take shape in 2018. (Naturally, this assignment also led to the creation of 30-plus biosimilar memes and a rewritten, biosimilar-themed Star Wars introduction — Biosimilar Wars, if you will. These were more popular than the presentation.)
A number of the predictions made in January 2017 reached tidy conclusions. We predicted Amgen vs. Sandoz would go to Sandoz; that we would see the launch of multiple biosimilars for the same reference product; and we would not see any movement with interchangeability beyond the already-released FDA guidance.
But some of the predictions were less clear-cut. In particular, Sjogren and I struggled to determine if the slow market in 2017 actually served as an “inflection point” for companies deciding if they wanted to continue investing in biosimilars. While we experienced disappointing uptake and legal settlements throughout 2017, we certainly didn’t see any drastic, sweeping moves away from biosimilars in company strategies. By our count, there were four changes or “great migrations” worth mentioning. Samsung-Bioepis shed its pure-play identity and leapt into novel drug development with Takeda, and Merck KGaA sold its biosimilar unit to Fresenius-Kabi. Allergan’s CEO said the company will not be pursuing future biosimilars outside of its current pipeline, and Pfenex made the difficult choice to put two biosimilar programs on hold until it could find development partners.
We ultimately argued that, at this point, most of the hesitation was on a company-by-company basis. However, this got me thinking more about the progress of the U.S. market in the grander scheme of things.
Do We Need To Change Our Thinking?
The other day, I was previewing a book chapter on Amazon, which led me to think more about the concept of progress in the biosimilar industry. The chapter, entitled “Progressophobia,” discusses our fears of making or acknowledging progress. Steven Pinker, the author of Enlightenment Now: The Case For Reason, Science, Humanism, and Progress, pointed out an almost innate proclivity for pessimism, as reflected in our tendency to read, report, and focus more often on negative news. We are regularly bombarded with news about threats of nuclear war, incidents of gun violence, and intense political upheavals. (And don’t get me started with social media.) As Pinker discussed, seeing these continual reports of violence, for instance, leads readers to assume violence levels have remained the same over time and nothing has improved — an assumption he researched and discredited in a previous book. These assumptions also blind us to the progress that actually has been made over time.
If we look at the U.S. biosimilar space, I’ll admit, it really doesn’t look great. Uptake is slow, and patent suits (and settlements) are putting seemingly impenetrable brick walls up. Scott Gottlieb has been winning the Internet with rhetorical fireworks about innovators’ “shenanigans” and the “rigged” “rebating mischief” keeping biosimilars down. Headlines like “Economics of Biosimilar Development Are ‘Currently Unstable’” and “Biosimilar Competition In U.S. Limited By Accumulative Regulatory Failures” paint a dismal picture.
Even though I am a skilled cynic, I’d hate to see the biosimilar industry fall into the “progressophobia” hole, especially as we continue to encounter only problem-related news. Yes, there are still mechanisms needed to help the industry gain solid footing. But in the U.S., we’ve made quite a bit of progress in just three short years. Medicare Part B and Part D plans have been revisited to encourage greater competition. Integral biosimilar concepts, such as extrapolation, are no longer questioned — at least as loudly. And, perhaps most importantly, real-world evidence dispelling safety and efficacy concerns continues to be released. In fact, a very important literature review was just released which reveals data from 90 different studies and reassures that fears of switching and biosimilar-caused immunogenicity overwhelmingly remain hypothetical.
Overall, the U.S. faces a number of frustrating biosimilar dilemmas, and the progress in the EU can make us impatient for a stronger market in the U.S. But, I’d also argue the EU’s success — proving biosimilars are safe, efficacious, and successful products — is overlooked in favor of the seemingly ongoing biosimilar strife we’re seeing in the U.S. As Avalere Health’s Gillian Woollett put it so nicely, the U.S. does not have to “reinvent the wheel" when it comes to safety. But through a quick survey of biosimilar-related headlines and the wide variety of hypothetical safety concerns still rampant here, it certainly seems a number of stakeholders are plagued by “progressophobia.” And one particular phrase continues to crop up in my mind that I’d argue has not yet proven true.
Has The Biosimilar-Wary U.S. Harmed The Global Biosimilar Industry?
When I entered this space a few years ago, I often heard the phrase: the success of the global biosimilar market would be dependent upon the U.S.’ success. This is a reasonable assertion, given the size and potential of the market and the prominence of the FDA and its biosimilar pathway.
But so far, I’d argue the global progress being made with biosimilars in spite of the crawling U.S. biosimilar market speaks volumes. Figures from the International Generic and Biosimilar Medicines Association (IGBA) reveal just how well biosimilars are performing in Europe. While the U.S. currently leads in terms of global biologics sales — 59 percent compared to 22 percent in the EU — only 2 percent of global biosimilars sales come from the U.S. A whopping 87 percent come from the EU.
But beyond sales figures, individual EU countries continue to make biosimilar-friendly moves — especially countries that have, to date, been relatively slow to move with biosimilars. Take France, for instance, which has had the lowest uptake of infliximab of the EU5 nations. The National Agency for Medicines and Health Products Safety (ANSM) has come out in favor of substitution for naïve patients as long as certain notification and monitoring conditions are met and the physician has not specified brand-only. (A legal decree is still needed, however, before this can become regular practice.) In addition to the development of “Similar Biologic Groups,” the country most recently began pushing a 70 percent target for initial prescribing rates.
Similarly, Belgium and Ireland, both of which hold the records for the lowest uptake of biosimilars in the EU, have begun to look for new strategies to encourage biosimilar use. In Ireland, the Department of Health released a consultation paper that aims to establish national biosimilar guidelines and the appropriate mechanisms for encouraging uptake in the country. In the last few years, Belgium signed a “pact for the future” for 2016-2018, in order to increase the use of and access to generic and biosimilar medicines.
There are still long journeys ahead for many EU nations, given these different approaches — it’s certainly not all sunshine and roses. But the EU is making strides with biosimilars despite the slow establishment of the U.S. market.
Now, it might still come to pass that the markets outside the U.S. will not be enough to sustain a thriving biosimilar industry. I’m well aware of the steep discounts in a number of nations that would make U.S. payers thrilled, but which raise logistical concerns for manufacturers. A well-performing U.S. biosimilar market could be a necessity for companies to ensure they remain profitable and invested in the space long-term.
However, I consider this to be a dangerous assertion to make. Instead, I’d argue it’s important to place greater emphasis on the experiences abroad through more peer-reviewed publications and biosimilar education campaigns. As Avalere’s Woollett argued in a recent article, those in the U.S. can “capitalize on the global experience with the same biosimilars elsewhere if we organize that experience in high-quality peer-reviewed papers…. [I]t is crucially important to do, as most healthcare professionals do respect the peer-reviewed literature.”
Many U.S. stakeholders’ concerns can easily be assuaged with more experience. I believe there is a place for editorial highlighting some of the “lows” of the current market. But biosimilars have come a long way — both in the U.S. and abroad. It’s going to be important to find ways to embrace and better publicize the past 12 years with biosimilars rather than dwell on our own market-centric disappointments.