As demand for biosimilars grows, so does the imperative to address barriers to their development. Christian Schneider reports from a recent panel discussion with industry experts he moderated.
With a record number of biosimilars set to be released in the US and European markets in the coming years, the worldwide market is forecast to reach $74 billion by 2030 (2).
The first biosimilar was approved in Europe in 2006 and, while uptake and savings did not initially meet expectations, manufacturing and testing of biosimilars has improved over time. What seemed impossible in the past – for example, biosimilar monoclonal antibodies – is now considered fairly mainstream.
After a slow initial uptake, there is growing recognition of the potential for biosimilars to offer a more affordable alternative to expensive biologic therapies, increasing patient access to life-changing therapies.
In the US alone, it is estimated that biosimilars have saved the healthcare system about $23.6 billion since the Food and Drug Administration (FDA) approved the first biosimilar in 2015 (3).
As more products lose regulatory exclusivity, they become ripe for biosimilar competition. Yet there are challenges to overcome on several fronts to ensure biosimilars reach their potential.
Flexibility to follow the science
Among the barriers is a long and expensive development process that requires manufacturers to conduct a series of clinical analyses to obtain regulatory approval.
Leah Christl, Executive Director and Head of Global Biosimilars Regulatory Affairs and Regulatory and R&D Policy at Amgen, said progress hinged on regulators maintaining their authority and the scientific flexibility to apply the best science. Christl was previously Associate Director for Therapeutic Biologics and Director, Therapeutic Biologics & Biosimilars Staff, at the US Food and Drug Administration.
“I’m concerned that the regulatory pathway for biosimilar development will not be flexible enough to ensure patients with rare conditions can get access to these drugs. We must continue to have conversations about the science and the regulatory pathways – among manufacturers and with the regulator,” she said. “We need to be forward thinking about our science.”
Elena Wolff-Holz, Global Head Clinical Development at Biocon Biologics and previously chair of the European Medicines Agency’s Biosimilar Medicinal Products Working Party (BMWP), is concerned that guidance documents regulators and companies rely upon may change with the development of the next European Regulatory Network Strategy in 2025 (4). Companies could be forced to omit certain programs.
“Or, they simply cannot cost effectively develop the biosimilars, especially because the guidelines and the interpretation of the guidelines currently do not converge,” she said. “There are major differences in what the FDA requires and what the EMA requires, for example, and this may lead to these tough decisions.”
The power of comparative analytics
While acceptance for biosimilars has increased among healthcare stakeholders, there is still some resistance to new biosimilar testing protocols.
Pharmacokinetic and Pharmacodynamic (PK/PD) studies that look at the totality of evidence, examining biomarkers on the mechanistic pathway to support biosimilarity, are shorter and less costly than clinical trials favored by traditionalists (5).
Christl said starting the biosimilar process using comparative analytics was the only way to fit development timelines, but educating stakeholders about the benefits would remain a challenge as the industry moves into new therapeutic areas.
“I think as we look at these data packages, and continue to look for efficiencies in these programs, the regulators, manufacturers, patient advocacy organizations, and therapeutic organizations all need to work together and dig into the education around that,” she said.
Martin Schiestl, Global Head Regulatory Affairs Policy of Sandoz Biopharmaceuticals, said part of the issue was the conservative approach to establishing the biosimilar pathway.
“It was really tough in the early days to ensure a comparable on the analytical level,” he said. “This delayed the maturation of the regulatory requirements. Today, what is needed is to show that the biosimilar is a true biosimilar.”
Wolff-Holz noted the complexity around efficiency, cost and manageability, especially for the next generation of products.
“The challenge is to provide clinicians with an appropriate level of competent evidence,” she said. “There should be a scientific question underlying each clinical study.”
Publishing results achieved in biosimilars in the market, she added, would also help foster confidence in their development.
Increasing the viability
It can be difficult to make the case for biosimilar development when market size does not support the return on investment.
Christl said the shift from blockbuster drugs, a natural target for biosimilar development, to rare diseases with their limited patient population has added to the challenge.
“You have to be able to get pharmacokinetic similarity studies or efficacy/safety studies,” she said. “How can you do that and work within the regulatory system to get the data that’s necessary to scientifically support the right assessment?
“Not every product is going to look the same in terms of development. So, there are some things that we need to think through to get the data that we need, putting patient safety at the forefront of development.”
In the case of combination products, Schiestl said it was about showing “the add-on effect in the efficacy endpoint. This add-on effect is small, but it leads to huge clinical trials, which are increasingly not sustainable. So, the best, most effective solution from my end is to push on efficient requirements for biosimilar approval.”
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References and notes
- Three imperatives for R&D in biosimilars, McKinsey, Aug 2022. https://www.mckinsey.com/industries/life-sciences/our-insights/three-imperatives-for-r-and-d-in-biosimilars
- McKinsey & Company. April 2022. Three imperatives for R&D in biosimilars. https://www.mckinsey.com/industries/life-sciences/our-insights/three-imperatives-for-r-and-d-in-biosimilars
- U.S. Generic and Biosimilar Medicines Report https://accessiblemeds.org/sites/default/files/2022-09/AAM-2022-Generic-Biosimilar-Medicines-Savings-Report.pdf
- European medicines agencies network strategy to 2025, HMA and EMA. https://www.ema.europa.eu/en/documents/report/european-union-medicines-agencies-network-strategy-2025-protecting-public-health-time-rapid-change_en.pdf
- Biosimilar development process, FDA. https://www.fda.gov/files/drugs/published/Biosimilar-Development-Process.pdf
