It’s not often that I focus on the manufacturing side of biosimilar development. This certainly isn’t because manufacturing strategies aren’t a critical part of biosimilar development. After all, we’ve seen in the recent year that manufacturing facility concerns have been a common reason for approval delays and Complete Response Letters (CRLs) from the FDA. But I recently spoke to Kate Hammeke, VP of Industry Standard Research (ISR), who was the lead author of a report entitled Biosimilars Manufacturing: Key Considerations and Expected Outsourcing Practices (AND is a fellow poet!). This report, the fourth edition of which was released in April 2018, surveyed experts in pharmaceutical companies responsible for outsourcing decisions to determine biosimilars’ impact on the biopharma manufacturing landscape.
The first edition of the report came out in 2014, which as we all know, was before the U.S. even saw its first biosimilar approval. And now, as the approvals (but not the launches) in the U.S. continue to stack up, the predictions of what this market could become in the upcoming years continue to advance. So, Hammeke and I sat down to discuss the biggest surprises or takeaways from this year’s report about the industry’s manufacturing goals. But the conversation also evolved to some of the larger trends Hammeke expects to see impacting the biosimilar players in the future.
What The Data Suggests About Future Biosimilar Outsourcing Demands
I generally avoid diving too deeply into a study’s data to allow the author’s work to speak for itself — and this article will be no exception. The 177 respondents to this report were primarily director-, manager-, or VP-level in mid-sized to large biopharmaceutical companies (not strictly biosimilar companies). Fifty percent of the respondents were located in North America, while the other 50 percent were spread globally in the EU and Asia. Of these respondents, only 27 percent of them are currently selling biosimilars. Looking into the future, there was a greater percentage of companies that have plans to sell biosimilars (17 percent) than there were companies that plan to manufacture them (7 percent). The report pointed out that this could bode well for the CMO sector as far as securing additional business.
But what I found interesting was that a percentage of respondents revealed their interest in pursuing biosimilars for their own originator products. Indeed, there are already 11 percent of respondents currently selling biosimilars to their own biologic. And of the 41 percent of respondents who are currently considering biosimilars for their pipeline, 17 percent of them would consider creating a biosimilar version of their own molecule. The end goal for this strategy would be to corner the market share for that specific product, and it wouldn’t be the first time we’ve seen such efforts undertaken. After all, in the small molecule space, a number of companies made investments in creating a generic version of their own drug.
“My suspicion is that all the different approaches used in the small molecule space between generics and the originator product will be tried in the biosimilar space,” Hammeke said. However, she’s curious to see if the biologics industry is able to employ similar strategies. For instance, in the small molecule market where the originator may have been available in a variety of different doses — for instance, 10 mg., 20 mg., or 50 mg. — the generics company may have decided to release a 15 mg. or a 40 mg. dosage. In the small molecule space, this approach is as easy as changing up the amount of API that’s in a dose, Hammeke explained.
In the biologics space, it might not be that easy. In fact, in some cases, we may verge into “biobetter” territory, in which companies seek to establish a different method of administration. A good example of this is Celltrion’s efforts to establish a subcutaneous version of infliximab, which the company will be submitting to the European Medicines Agency (EMA) in the upcoming months.
Now, in the biosimilar market, which has been facing the hurdles of misinformation and fear-mongering, there’s a potential positive that could come from this “market cornering.” Innovator efforts to stir up anxiety about the quality and safety of biosimilars may end up being thrown out the window. “In the case when the manufacturer of the originator starts making biosimilars of that originator, I think some of the innovator-driven arguments that currently exist about the safety of biosimilars and interchangeability will have a harder time standing,” she said.
But she also pointed out the challenges that market cornering can have on the manufacturing and outsourcing landscape. As you might expect, when choosing a CMO for outsourcing biosimilar manufacturing, prior experience working with the reference product bodes well. While 31 percent of respondents would look for low-cost manufacturing, 23 percent said they would look at a company’s history of manufacturing the originator. “Whether it’s a complex biologic, whether its complex high potency or something with a schedule, emerging and middle-size companies approaching a CMO want to know the company they’re hiring had success in that product area,” Hammeke added.
That said, however, we may start to see (or already may be seeing) strategies that can keep companies from securing the best CMO for their biosimilar products. In fact, Hammeke expects that a lot of the CMOs responsible for making the innovator are likely to receive requests from biosimilar companies making the same product.
“I think there could be a lot of secret deals going on in the future. Hypothetically, if Reference Company A were outsourcing its leading drug X to a CMO, they probably wouldn’t want Biosimilar Company A or B that both have biosimilars of X to be working with the same CMO,” she explained. So, contracts could be designed limiting the manufacturing of product X to only the originator product of that drug. This could introduce capacity concerns and be a challenge for companies seeking outsourcing partners in a quickly crowding biosimilar market (especially for the biologics that draw a lot of interest from biosimilar makers).
Brace For A Future Of Biobetters
When it comes to the future of the industry, Hammeke expects we should brace for some “powerful organizations to be built on biosimilars,” but in the long-run, biobetters might be the best long-term strategy. Though tweaking the reference product will require some level of clinical research to support the claims that the product is better, it could be a more efficient pathway for getting a product onto the market. In some cases, it may enable companies to avoid some of the litigation that affects biosimilars, given that a biobetter is not just a highly similar “copy” of the molecule itself.
In fact, another finding in this report that surprised me was just how many respondents revealed that their company’s focus was not just on biosimilars but also on biobetters. Upwards of 50 percent of respondents (47 percent to be exact) revealed that biosimilars and biobetters are part of their corporate strategy, depending on the drug. Compare this to 34 percent of respondents whose companies are focused on biosimilars and 19 percent solely on biobetters. When given the opportunity to share why their companies chose this dual strategy, respondents highlighted several common themes. The most regularly provided answers were that pursuing both was the best approach for the geographic regions being targeted; having biobetters in the pipeline could be a differentiating factor following the increase in biosimilar comfort and adoption; and biobetters could widen the access to the product or bolster profitability.
When I asked Hammeke how she’d expect the question of biosimilar versus biobetter to be answered if ISR were to hold this survey again in five to seven years, she said she expects we’re going to see a larger percentage choosing to tackle both. She also said we’re likely to see a decrease in the number of respondents who are only focused on biosimilars, “because improving upon an existing biologic offers an opportunity to be compensated for the cost of developing the ‘better’ aspect.”