Tony Hagen is senior managing editor for The Center for Biosimilars®.
Joseph E. McClellan, PhD, MBA, discussed navigation of regulatory hurdles as the company continues its quest to line up distribution partnership deals across the globe.
Considering Alvotech doesn't have any biosimilars approved, some may question why the company is signing biosimilar distribution deals all over the globe. The answer, according to Joseph E. McClellan, PhD, MBA, Alvotech's chief scientific officer, is that the Reykjavik, Iceland-based company aims to obtain regulatory approvals for multiple products almost simultaneously in multiple countries and then launch.
The worldwide market for biologic originator drugs exceeds $300 billion and is growing at a 10% clip each year. “We’re in the earlier stages of a long-term expansion for the global biosimilars market,” he said in a recent presentation on the company’s expansion strategy and the challenges of entering markets with different regulatory standards for biosimilar approval.
On November 24, 2020, Alvotech announced a contract with CCHT Biopharmaceutical of Changchun, China, and Yangtze River Pharmaceutical Group, of Taizhou, China, to commercialize 8 biosimilars in China. The deal follows on the heels of other announced partnerships for distribution in North America, South America, Europe, the South Pacific, Africa, and the Middle East. Alvotech has biosimilars in development for autoimmune diseases, ophthalmology, and oncology.
Meeting Different Standards
Regulatory standards differ from country to country. While regulators in Europe and the United States tend to hold that comparative clinical efficacy trials are not of significant value in demonstrating biosimilarity, this is not the case elsewhere, where animal and in-human studies of biosimilars may be required to complete the package of evidence required for consideration of approval.
Analytical, pharmacokinetic (PK) studies are the foundation of biosimilar approvals in the United States, but when it comes to clinical studies—although they already were performed for originator drugs—the goal for some regulatory authorities may be an added level of reassurance, McClellan said.
“In vitro tests for looking at function are much more sensitive, and as you progress from binding assays and cell binding assays, and function cell assays, your sensitivity decreases for demonstrating similarity," he said. "Of course, as you move into in vivo animal models and human clinical trials, the clinical relevance is deemed to be more significant. It’s that balance. If you’re going to do an in vivo animal model, what are you trying to solve there. It’s likely it’s about providing the confidence about the safety of the molecule."
China tends to require animal studies as a condition of doing human clinical studies, as well as the use of locally sourced reference product for the comparator drugs. It would be easier if the reference product required for testing could be standardized across the globe, McClelland said. “How do you include China when you want to use 1 product for your clinical studies, whether PK or a comparative patient study? It’s an interesting challenge.”
Such requirements also make it difficult for Alvotech to execute on another of its strategic goals, which is to perform PK similarity and clinical confirmatory studies almost in parallel to one another to speed up development and get to regulatory approval faster. With regional partnerships across the globe, “We also have that commitment to ensure that we can develop our biosimilars in a speedy manner,” McClellan said.
China is very strict about requiring that nonclinical studies be performed before clinical studies, he added.
Smoothing out the obstacles in this quest means that Alvotech has to engage with regulatory authorities from individual countries early in the development process to shape the biosimilar development project and understand local priorities for approval, McClellan said.
Japan, also one of the world’s largest markets for biologics, presents a different challenge. That country’s regulatory authority requires that subjects of Japanese origin be included in clinical studies.
Another Alvotech goal is to develop commercial scale operations for its product development efforts. The company seeks to develop biosimilars for approvals in all indications of the reference products in the markets it enters.
At its headquarters in Reykjavik, Alvotech has a 140,000-square-foot facility for manufacturing and product development. It also has a production center under construction in Changchun that will have the capacity for producing 2.5 million “patient treatments” a year. The project is a partnership with the Changchun High & New Technology Industry Group.
The company has research and development operations in Julich and Hanover, Germany; Virginia; and Zurich, Switzerland.