What Challenges Lie Ahead for Eventual Biosimilars of Advanced Therapy Medicinal Products?

Advanced therapy medicinal products (ATMPs), including gene therapies, cell therapies, and tissue engineering products, are providing groundbreaking approaches to treating rare diseases. However, the costs associated with these drugs are expected to pose challenges for affordability and the sustainability. A newly published paper looked ahead to the potential for—and challenges related to—biosimilars of ATMPs.

According to the paper, the list price for currently marketed ATMPs ranges from $18,950 for a tissue-engineered therapy to $1,206,751 for a gene therapy, and these high prices do not include purchasing, inventory, and management costs that could substantially increase overall treatment costs. While these high list prices may serve to incentivize new product development, write the authors, they limit patient access and could lead to marketing withdrawals for commercial reasons.

Thus, write the authors, competition will be key for improving the affordability and availability of these drugs in keeping with progress made on current generic and biosimilar products that have increased access to a number of therapies and reduced costs.

However, developing a robust ATMP biosimilars market would be challenging; products classified as ATMPs can be diverse, and current regulation focuses on product-specific innovation. The authors propose that a separate regulatory pathway for approving ATMP biosimilars may be required, particularly because a demonstration of biosimilarity would involve complex active substances, and autologous or allogenic patient factors. Another challenge is the fact that few validated biomarkers for biosimilarity have been identified, and regulatory systems will need to address the complexity of ATMPs and the challenge of comparing outcomes of highly individualized therapies.

One crucial factor that could impact development of ATMPs is the cost and difficulty in accessing the innovator product for the purpose of development; even with current biosimilars and generics, drug makers report challenges in obtaining enough samples to conduct testing, and such products as ATMPs may have even greater hurdles.

If phase 3 clinical studies are required to address any residual uncertainty about the biosimilarity of products, those, too, could prove to be cost prohibitive and challenging with respect to enrollment of patients with rare diseases.

Finally, note the authors, current regulatory frameworks are focused on innovation in the ATMP area, not on increasing competition, so regulators would need to work on aligning incentives for research and development with healthcare budget constraints.

Reference

Seoane-Vazquez E, Shukla V, Rodriguez-Monguio R. Innovation and competition in advanced therapy medicinal products [published online February 15, 2019]. EMBO Mol Med. doi: 10.15252/emmm.201809992