Duke Publishes Recommendations for Developing CGT Biosimilars

In light of high costs for current cell and gene therapies (CGTs) and promise of biosimilars to lower costs on biologic drugs, the Duke Margolis Institute for Health Policy published policy recommendations for developing a robust competitive market for biosimilar CGTs.¹

The FDA has approved numerous innovative cell and gene therapies, highlighting a rapidly expanding field that faces significant financial challenges and regulatory hurdles, necessitating strategies to promote future biosimilar competition to improve patient access and mitigate high treatment costs. | Image credit: natali_mis - stock.adobe.com

Although CGTs have been transformative in treating serious conditions like genetic disorders and cancers, they are extremely expensive, posing financial challenges for both patients and payers. One report found that the prices of the 8 oncologic gene therapies approved by the FDA by July 2023 range from $65,000 to $475,000, and the prices for the 8 nononcologic FDA-approved CGTs range from $630,000 to $3.5 million.² The introduction of biosimilars could help reduce costs and improve access, but the complexity of creating CGTs makes the process of developing biosimilars more difficult.¹ Without supportive regulatory frameworks and policies to guide biosimilar development, competition in the CGT market may remain limited.

“Promoting future biosimilar competition in the CGT market, where feasible, in anticipation of patent and other exclusivity expiration for these products, should be explored to the greatest extent possible,” the authors wrote.

The authors made 6 recommendations:

1. Issue guidance on CGT biosimilarity within the Biologics Price Competition and Innovation Act (BPCIA) pathway and promote regulatory flexibility for biologics to support the development of follow-on CGT therapies.
2. Prioritize the development of gene therapy biosimilars and address regulatory gaps for both gene and cell therapies.
3. Enhance regulatory review processes and expand expertise within the FDA to better accommodate CGT biosimilars.
4. Promote the standardization of manufacturing platforms to reduce the high costs and complexity of CGT production and encourage more market entry.
5. Facilitate CGT biosimilar development through knowledge transfer, disclosure incentives, and clearer patent laws.
6. Establish a CGT biosimilar development demonstration program to identify key knowledge, technology, and regulatory gaps that could inform future policy initiatives.

The FDA's biosimilar approval framework under the BPCIA needs adaptation for CGT biosimilars due to their complexity, the authors noted. Additional guidance on manufacturing, testing, and regulatory standards is essential for ensuring biosimilarity, particularly regarding long-term safety and effectiveness. Clearer standards for manufacturing processes, clinical trials, and intellectual property will also be vital for establishing a viable CGT biosimilar market.

Standardizing manufacturing platforms could improve efficiency, scalability, and reduce costs of CGT biosimilar development. Approaches like centralized and decentralized manufacturing, as well as point-of-care facilities, can enhance production. Automation may also lower labor costs and variability. However, achieving industry-wide standardization is complex due to diverse CGT types and the need for good manufacturing practices.

Organizations such as the United States Pharmacopeia and he FDA are working to establish standards. The FDA’s Advanced Manufacturing Technologies Designation Program could expedite reviews for standardized products, supporting their market adoption. Balancing innovation and biosimilar development is essential as standard-setting evolves.

Although many patents exist, current disclosure practices may not meet legal requirements, leading to key manufacturing techniques being kept as trade secrets. This lack of transparency complicates the creation of biosimilars and extends periods without competition.

Insufficient disclosures hinder knowledge transfer among manufacturers. Contract development and manufacturing organizations could help, but more investment is needed in their capabilities. Legislative measures might promote sharing critical manufacturing information in exchange for faster FDA approvals, aiding biosimilar development.

To improve manufacturing for CGTs, a congressionally funded demonstration program could be created to replicate the manufacturing processes of approved CGTs. This initiative would involve collaboration among academia, the FDA, the National Institutes of Health, standards organizations, and CGT manufacturers. The program would aim to develop analytical testing methods to ensure no clinical differences between originator CGTs and biosimilars, evaluate patent disclosure adequacy, and address manufacturing challenges. It could also pave the way for establishing a CGT biosimilar Center of Excellence to build expertise in complex therapies.

The authors concluded, “These recommendations aim to navigate the complexities of biosimilar CGT development and introduction, in order to enable the health care system to benefit from both novel treatments and cost-effective biosimilar alternatives when the innovator products lose their exclusivity. As the CGT field advances, collaboration between Congress, regulators, industry, and other key stakeholders will be paramount in clarifying the path forward, ensuring that the promise of CGTs is accessible to all patients in need.”

References

1. Early recommendations for promoting future cell and gene therapy competition through biosimilars. Duke Margolis Institute for Health Policy. September 23, 2024. Accessed October 8, 2024. https://healthpolicy.duke.edu/publications/early-recommendations-promoting-future-cell-and-gene-therapy-competition-through

2. Shaw ML. High-cost gene therapies present reimbursement, access challenges. AJMC^®. November 8, 2023. Accessed October 8, 2024. https://www.ajmc.com/view/high-cost-gene-therapies-present-reimbursement-access-challenges