The biosimilars landscape is growing as market factors, such as pricing pressure, advanced bioprocessing and analytical technologies, and upcoming patent expirations for innovator biologics drive the development and commercialization of biosimilar products.
There are 45 biosimilars approved in the United States, which represents amazing progress over the past 10 years or so, remarks John Gabrielson, senior vice-president at JSR Life Sciences and head of Similis Bio.
Still, Gabrielson notes that the US lags roughly 10 years behind Europe in marketing biosimilars, with the first biosimilar, Zarxio (filgrastim-sndz), approved in the US in 2015 (1). “We’re looking at close to two decades now of experience worldwide with biosimilars,” Gabrielson says. “I think we’ve come a long way. I think the market is extremely strong right now, but there are still some challenges.”
Zara Bukhari, a PhD student in biochemistry at University of the Pacific, points out that bringing a biosimilar to market can be arduous, in particular because the developer has to have a large set of analytical similarity data when compared to the innovator biologic.
Interchangeability
Another point that a biosimilar developer must contend with is interchangeability, Bukhari also points out. For example, with a small-molecule drug, it is simple to replace that drug at the pharmacy level with a generic because their similarity has been demonstrated. However, it is not the same when dealing with biologics because biologics are larger and more complex molecules. Thus, to show that a product is exactly similar, that it would have the same potency, the same kind of reaction in the body, any immunogenicity, or that it would have the same kind of impact that an innovator has, is quite challenging, Bukhari emphasizes.
“You need to show that they are interchangeable, say, if the innovative product is not available, then the doctor can feel comfortable prescribing a biosimilar,” Bukhari says, pointing to the fact that the comfort level of physicians is a significant factor in how well received a biosimilar is in the market. “Even though FDA has things in place, and there have been many talks that there is much money spent on a clinical trial to show that [a biosimilar and its innovator product are interchangeable], much of the time, the comfort level or the hesitancy is there among doctors—and patients—in prescribing the same medicine as that of the innovator. Even though [the biosimilar] is at a lower price, and you’ve established that it is pretty stable, will do the same thing in your body. That is a hindrance in biosimilars, I would say, the comfort level that doctors and patients feel in terms of getting an alternate medicine that would have the same impact,” Bukhari explains.
Lack of market uptake?
Noticeably, sales of biosimilars have not been as high compared to innovator biologics, despite being on the market for years, Bukhari remarks.This points to less-than-stellar uptake.
Gabrielson agrees, stating that market uptake has not met expectations in certain cases. This is partly due to the hesitancy among doctors and patients regarding the difference between biosimilarity and interchangeability, both Bukhari and Gabrielson specify.
“I think [this perception] is unique in the US market compared to other areas of the world,” Gabrielson says. “In the US, a biosimilar can be approved as a biosimilar without being interchangeable, or it can be approved as a biosimilar that is interchangeable, [which requires] switching studies as part of the clinical arms of the biosimilar approval, at least in some cases, to demonstrate that the product is, in fact, interchangeable.”
Gabrielson, however, considers that it may be a mistake to allow these two conditions of biosimilar approval in the US (i.e., biosimilar approved without interchangeability or biosimilar approved with interchangeability). “I feel like what [has been] created is two classes of biosimilars in the US market, where some are judged to be of ‘higher’ quality because they’re interchangeable, which wasn’t the intention. … A better model would be one where any biosimilar that’s approved, that goes through the rigorous approval process, by regulators in the US or elsewhere is automatically deemed to be interchangeable with its reference product, similar to the EU designation system. I think that would ease the burden,” Gabrielson says.
Easing the way for market uptake of biosimilars also requires discussion, Gabrielson notes. There is a need for discussion between patients and doctors and alignment among physicians with a goal toward raising the comfort level in prescribing biosimilars in lieu of the innovator product. The responsibility in changing the misperception that there exists a tier of “higher-quality” biosimilars falls upon multiple areas.
“It’s not a single organization or even a single sector that needs to take the lead in this. It’s about multiple groups working together to really change that mindset,” says Gabrielson. Certainly, the industry needs to take a role as well as regulators, he adds. Furthermore, he believes that Congress may also need to step in and change the underlying law that dictates interchangeability.
“[Interchangeability] is built into federal and state laws, which doesn’t provide FDA with as much flexibility as is needed,” Gabrielson states, going on to say, “but most of it really comes down to education.” Gabrielson specifies that education is needed in terms of: how to educate physicians on what biosimilars are, their quality, how rigorously they’re tested to ensure that they are safe and efficacious; and that, if a biosimilar doesn’t have the interchangeability designation, it is still a safe and effective treatment.
“Much of it really is just education materials that can be created by, for example, trade organizations or companies speaking to physicians, and, ultimately, even directly to patients,” Gabrielson says.
Dealing with challenges
Other hurdles to bringing a biosimilar to market include the availability of the reference biologic and the batch-to-batch variability of that reference product; this is on top of the complexity of the molecule, notes Bukhari. “[Furthermore,] since you’re dealing with biologics, you cannot have exact true copies,” she adds. “The process and manufacturing aspect of it is patented, it’s not released. So, [a biosimilar developer] would need to figure it out [for themselves] and understand the process, and make it cost effective, all at the same time.”
Add to that the time it takes to bring a biosimilar to market and the challenge of navigating the regulatory pathways. “As mentioned earlier, [companies] have to provide much more CMC [chemistry, manufacturing, and controls] data for biosimilars compared to the innovator, and that takes time. [Companies] have to establish more steps, and need to have much more stability data available to show that [the biosimilar] product is actually doing what it is supposed to do,” Bukhari explains.
Another hindrance to progress is the ideology of adopting the innovation aspect and including it to justify one’s data to FDA, Bukhari adds. “Say [a company has] taken up an innovative method to produce a biosimilar, then that method also has to be validated. That validation data also has to be given to FDA, and that requires more time and cost,” she says.
“When we think about what it takes to bring a biosimilar to market compared to what it takes to bring an innovative product to market, of course, there’s a much lower clinical barrier, fewer clinical requirements. [It’s] abbreviated for a biosimilar,” says Gabrielson. However, Gabrielson clarifies, what most people don’t realize is that the amount of data from a CMC perspective, and particularly data demonstrating analytical similarity, is the same or higher than what it would take to bring an innovative product to market.
“There’s so much work that goes into demonstrating, analytically, that a product is comparable or similar to its reference product in order to achieve that type of regulatory approval,” Gabrielson states.
On the pricing pressure aspect in the biopharma market, Gabrielson asserts that pricing pressure is a central theme in biosimilars. “That is why these products exist, fundamentally,” he remarks, “to make life-changing medicines more available, more accessible, and more affordable to patients throughout the world. I think it makes sense that there is pricing pressure in this market, because I think everyone’s goal with this is to make medication more affordable to patients.” Thus, rather than a hindrance, and rather than existing in a mindset where developers need to find a way to overcome pricing pressure, Gabrielson points to pricing pressure on the market as the reality, and should be perceived as such.
“It’s a feature of the system, not a bug,” Gabrielson states, explaining that what biosimilar developers need to be doing is figuring out creative and innovative ways to build businesses that can be successful in an environment where there is going to be sustained, consistent pricing pressure. “Pricing pressure can come from lower priced, brand name biologics when they come off patent, it can come from competing biosimilars, but that’s the market. It’s not exactly like the generics market, but there are some parallels between what [is being seen] with biosimilars and what [has] already [been] seen with generics in terms of that pricing pressure. So, a good question that really needs to [be] asked [of] developers is, how is [a] particular product viable commercially, and even differentiated in the marketplace, in the face of this type of competition?”
Reference
1. FDA. FDA Approves First Biosimilar Product Zarxio. Press Release, March 6, 2015.
About the author
Feliza Mirasol is the science editor for BioPharm International.
Article Details
BioPharm International
Volume 37, No.3
March 2024
Pages: 8–9,29
Citation
When referring to this article, please cite it as Mirasol, F. Moving Biosimilars Forward in a Hesitant Market. BioPharm International 2024, 37 (3), 8–9,29.
