BioRationality: Biosimilars Are Not Doing Well—Time for a Change in Perspective

Dozens of reports that have come out recently have estimated how much money biosimilars will save but do not mention that there is a reduction in the number of market entrants entry for new biosimilars that needs attention.

Biosimilars are not doing well at all. The first half of 2023 saw only 1 biosimilar approved in the United States and 2 in the European Union. The trend graph tells the story better. While the United States has 41 FDA-approved biosimilars and the European Union has 77 European Medicines Agency (EMA)-approved biosimilars, these numbers are misleading without mentioning that these numbers represent a small fraction of molecules.

Approved biosimilars account for only 11 molecules in the US and 18 in the EU, when there are 266 choices of FDA-approved therapeutic proteins that can be marketed as biosimilars that are not under patent protection. Unless there is a significant rise in the molecular choice for biosimilars, and multiple biosimilars for each, the promise of biosimilars will not be fulfilled.

Much of this conflict for biosimilars can be attributed to misconceptions about biosimilars created advertently—by those who do not want to see biosimilars—and inadvertently—by those who do not understand biosimilars. Here is a list of these misconceptions and their resolutions:

• Biosimilars take $100-$300 million and 6 to 8 years to develop. These numbers are, in my opinion, highly exaggerated. For many molecules with pharmacodynamic markers, it should cost much lower and not take more than 3 years to develop provided the development plans are science-based and the scores of regulatory dossiers available to examine from EMA and FDA. There is no need for multiple meetings with the FDA, as each meeting takes 4 to 6 months to schedule.
• Monoclonal antibodies (mAbs) should be the most critical category and many contract development and manufacturing organization now only offer Chinese hamster ovary cell service. Many products are expressed in E. coli, and its use is rising. I think this is a much better choice for development even for full-length antibodies.
• Biosimilars need phase 1 and phase 3 studies to prove biosimilarity. Phase 1 studies are clinical pharmacology trials and phase 3 studies assess comparative efficacy between the biosimilar and reference product in patients. This differentiation is needed to reduce the cost of studies. For example, using a restrictive selection of study participants, since the purpose of these studies is to compare, not characterize, the products.
• Follow the high market mAbs to make the biggest impact and profit. With 9 adalimumab biosimilars approved by the FDA, it’s likely they will not all obtain a great market share when they launch, which could reflect a herd mentality to capitalize on Humira’s (reference adalimumab) loss of exclusivity rather than a commitment to bringing biosimilars to patients in need.
• Capital expenditure (CapEx) is too high to start development. Use of newer technologies, like continuous manufacturing, have lowered CapEx significantly.
• Oncology products have the highest potential or return on investment. The potential for profits depends on market competition, not on the nature of the drug.
• The FDA complete response letters (CRLs) for a biosimilar application can ruin a company’s chances for approval. Every biosimilar developer has been hit with a CRL at one point or another and there is still hope for companies to bring the product to market. One possible next step is to let a qualified third party conduct the final analytical assessment comparison.
• High-yielding cell lines are required, but they cost a lot. On the contrary, low-yielding cell lines provide batches with higher consistency, making it easier to qualify a biosimilar. The cost is in the carbon input, so a high-yielding cell line merely reduces the size of the bioreactor, not the cost of goods.

There are over 114 biologic products with that have lost or will lose patent protection by 2027, making them ready for development as biosimilars now. Some of the products already have biosimilars in development or on the US market (adalimumab, etanercept, filgrastim, natalizumab, etc) but many do not have any biosimilars in the pipeline. These products without biosimilar development represent a unique opportunity for companies to seize market share and help create a healthy competitive biosimilar market.