Opinion: Five years after Kymriah: Ensuring the next cell and gene therapies reach patients

Five years ago today, the Food and Drug Administration issued a landmark approval for Kymriah, the first gene therapy available in the United States.

Cell and gene therapy products can transform how certain diseases are treated, offering life-extending and potentially curative benefits for patients living with life-threatening or debilitating diseases.

Propelled by significant research and development investments and scientific advances, the cell and gene therapy market has since experienced tremendous growth. Regulatory agencies around the world have approved a number of cell and gene therapy products — including eight new therapies in the United States — that target diseases with high unmet needs, ranging from cancer to retinal diseases.


Based on a robust cell and gene therapy pipeline, experts forecast a wave of new approvals in the coming years, with the Alliance for Regenerative Medicine predicting 2022 could be record year for new gene therapies to treat rare diseases.

This trajectory holds substantial promise for patients worldwide. But right now the science is ahead of the U.S. health care system, leaving gaps that affect access —the existence of a therapy is immaterial if patients can’t access them.


To realize the full potential of these therapies, it’s imperative to address existing challenges, such as payment and affordability-related barriers and reimbursement issues.

Addressing reimbursement

Reimbursement — paying doctors and health care centers for the treatments they have administered — is an important part of U.S. health care. Ensuring that cell and gene therapies are sufficiently reimbursed is essential for ensuring patient access.

Reimbursement isn’t as simple as sending an invoice and receiving payment. Coverage (a payer’s decision to provide benefits for a specific product), coding (a unique identifier for a medicine) and payment levels (the amount an insurer will pay) affect how a product is reimbursed — and each of those factors can vary based on the market, payer and therapy.

In the first few years after Kymriah’s approval in the U.S., there wasn’t a specific diagnosis-related group code for autologous cell therapies, a specific type of cell therapy in which a patient’s cells are collected, genetically modified, and then given back to the patient. The lack of a DRG code created uncertainty among providers about whether they would be appropriately reimbursed for the services they provided. The reimbursement landscape in the U.S. has since evolved: the Centers for Medicare & Medicaid Services issued and refined a diagnosis-related group code for autologous cell therapies, and a change in the status of the new technology add-on payment, which enables an additional payment to hospitals on top of the DRG payment amount.

These measures represent meaningful steps toward capturing the uniqueness of autologous cell therapies. But the frequent changes likely have contributed to confusion among health care providers about how to report the therapies and their charges.

Billing and coding errors resulted in significant differences in payment, and many hospitals were underpaid in 2019 and 2020, according to an analysis of Medicare payments by my colleagues on AmerisourceBergen’s consulting team. The disparities in payment underscore the importance of educating health care providers and their staff on the latest reimbursement changes and helping them master the dynamics of coding and billing, especially until a more permanent reimbursement solution is developed.

With more than 1,000 clinical trials now underway worldwide for cell and gene therapies, it’s increasingly important to establish solutions that address the current reimbursement challenges and establish more standardized pathways to cover the next wave of therapies and ensure they can reach the patients who need them. As regulators develop new guidance, biopharma companies should prioritize payer and stakeholder engagement earlier in the development life cycle to address questions related to payment and coverage decisions, such as:

  • What sites of care will administer it?
  • What endpoints will be meaningful to payers?
  • Can existing codes be used for the therapy or does the developer need to seek a new code?
  • Are payers open to novel payment arrangements?

Driving access through alternative payment models

Payers face this central question when evaluating cell and gene therapy products: How do we balance the potential long-term clinical value with the cost of the therapy and uncertainty regarding long-term durability at the time of regulatory approval? That challenge is compounded by the fact that many cell and gene therapies are one-time treatments, and patients can switch insurance carriers throughout their lifetimes, meaning the insurer that reimburses the cost of the treatment may not reap the benefits of saved health care costs down the road.

Historically, the vast majority of payers in the U.S. have used traditional techniques such as formulary or utilization management tools to manage the costs of cell and gene therapies. But payers have increasingly expressed interest in alternative payment models, such as reinsurance and outcomes-based agreements, in which payments are ultimately based on how well a treatment benefits patients. While outcomes-based agreements are particularly relevant for products with limited long-term clinical data and small patient populations, such as cell and gene therapies, certain factors — including the Medicaid best price policy — have prevented more widespread adoption of these agreements. A recently finalized rule by CMS aims to mitigate some of the potential challenges and concerns related to the Medicaid best price and foster more outcomes-based agreements between payers and biopharma companies for cell and gene therapies. That said, legal and compliance issues still pose barriers to these agreements.

Continued innovation in contracts and financial partnerships is essential to unlock access to cell and gene therapies. Biopharma companies and payers need to be flexible, agile, and open-minded in considering arrangements like outcomes-based agreements that better account for the long-term value and clinical outcomes over the term of the patient’s insurance policy. Considering the effort required to negotiate the value structure of outcomes-based agreements, I anticipate payers will be increasingly interested in participating in outcomes-based agreements for cell and gene therapies if there is a portfolio of products.

AmerisourceBergen, which I work for, provides pharmaceutical distribution services as well as solutions to help biopharma companies at every stage of the product lifecycle. The company is exploring ways to facilitate outcomes-based agreements that are objective, measurable, and easy to manage. We recently developed an outcomes-based agreement model for cell and gene therapies that aims to reduce financial exposure for biopharma companies, payers, and their client groups (namely employers with members who are eligible for these treatments) with the goal of improving patient access to cell and gene therapies.

Capitalizing on the momentum

The next five years hold tremendous promise for cell and gene therapies, including the potential to usher in allogenic cell therapies. Often referred to as “off-the-shelf,” allogenic cell therapies can be collected from a donor and then used to treat many patients — rather than collecting and modifying each patients’ cells — easing some of the manufacturing-related challenges associated with autologous cell therapies.

Meanwhile, the FDA continues to explore new initiatives to help accelerate the development of cell and gene therapy products. The director of the FDA’s Center for Biologics Evaluation and Research, which regulates biological products for human use under applicable federal laws, recently shared his interest in establishing a gene therapy program in which sponsors would receive real-time feedback about their development programs from FDA reviewers. The program would help to inform the best approaches in developing gene therapies.

Based on the current pipeline of cell and gene therapy products, it’s possible that between 54 and 74 CGT products will be approved in the U.S. by 2030. Of course, even if these products receive approval and developers have the capacity to manufacture them at scale, the full potential of these therapies won’t be realized unless the existing reimbursement and access barriers are addressed.

As the pipeline of cell and gene therapies continues to expand, it’s critical that the biopharma industry and the health care system create more standardized reimbursement pathways and introduce solutions that reduce barriers for the providers administering the therapies and the patients who need them.

Lung-I Cheng is the vice president of cell and gene therapy at AmerisourceBergen.

Source: STAT