Introduction to Biosimilars
Insulin biosimilars offer great promise to expand access to life-saving insulin therapy for millions of patients worldwide struggling with the rising costs of branded insulin products. Biosimilars provide a cost-effective alternative to reference biologics that have lost patent protection. With several insulin biosimilars in late-stage development or under regulatory review, the future holds the very real potential to help control skyrocketing diabetes treatment costs.
The Science Behind Biosimilars
All biologic medicines are complex proteins produced using living systems like yeast, bacteria or animal cells. Due to this inherent complexity, biologics cannot be perfect copies of reference products. However, extensive structural and functional analysis can demonstrate that a biosimilar is highly similar to its reference product without any clinically meaningful differences in safety and efficacy.
Insulin was one of the earliest approved biologics dating back to the 1920s. Since then, significant scientific advancements have improved insulin manufacturing processes and formulation, yielding products with enhanced pharmacokinetic and pharmacodynamic properties. Modern biosimilars leverage these gains by replicating the structure, safety and effectiveness of approved insulins through rigorous analytical, non-clinical and clinical testing programs.
The Regulatory Pathway
Major regulatory agencies like the U.S. FDA, EU EMA and WHO have established a rigorous step-wise process for biosimilar approval. Manufacturers must initially perform analytical studies to prove biosimilarity at the molecular level. This is followed by non-clinical pharmacology and toxicology evaluations.
The pivotal step involves a clinical trial program comparing key product attributes head-to-head against the reference product. For insulin, the pharmacokinetic-pharmacodynamic endpoint is typically based on glucose clamp or euglycemic clamp techniques. Any meaningful differences must be ruled out. Post-marketing requirements also ensure ongoing monitoring of safety, immunogenicity and performance.
Potential Cost Savings from Insulin Biosimilars
Insulin is one of the highest expenditure biologic therapy categories, with global sales exceeding $25 billion annually. However, insulin costs have spiraled out of reach for many due to lack of generic competition. Biosimilars could help address this inequity.
Early European experience with filgrastim and somatropin biosimilars showed average price reductions from 15-35% compared to reference products. Assuming a similar discount range, insulin biosimilars may reduce treatment costs by $3,000 to $7,000 per patient annually in the U.S. alone. Wider global availability could impact tens of millions with reduced diabetes therapy costs.
Biosimilar uptake also fosters market competition, exerting further downward pressure on prices. As more manufacturers enter theFollow on Biologics Market with approvals, list prices continue decreasing incrementally with each new entrant. Over time, average biologic treatment costs could fall up to 50% from current levels.
Progress in Insulin Biosimilar Development
Encouragingly, several insulin programs have already achieved key regulatory and commercial milestones. India’s Biocon/Mylan was the first to gain US FDA approval for its insulin glargine biosimilar Semglee in 2019, entering at a 15% discount. South Korea’s Hanmi also received approval there for its insulin glargine.
Other notable programs include:
– Eli Lilly/Boehringer Ingelheim’s insulin glargine completed Phase 3 testing.
– Samsung Bioepis’ insulin glargine and insulin lispro combinations are under EMA/FDA review.
– Mylan/Biocon’s insulin aspart is in Phase 3 trials.
– Many Asian/European manufacturers are developing human insulin, insulin aspart and insulin lispro biosimilars.
As these progress through final approvals over 2021-2023, insulin affordability should start improving markedly across major markets. Wider global regulatory harmonization would further expedite biosimilar uptake in lower-income regions.
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