Navigating the Complex Landscape of Gene and Cell Therapies: A Strategic Guide for Employers
Gene and cell therapies represent a groundbreaking frontier in modern medicine. They offer the potential to treat or cure diseases at their genetic root. Unlike traditional therapies, which often manage symptoms, gene and cell therapies aim to address underlying biological mechanisms, transforming patient outcomes. According to the American Society of Gene and Cell Therapy (ASGCT), over 2,000 gene therapy clinical trials are underway globally, with several therapies already approved by regulatory agencies (1).
Gene therapy involves altering a patient’s genes to treat or prevent disease, often using vectors such as modified viruses to deliver genetic material into cells. Cell therapy, on the other hand, uses living cells from either the patient (autologous) or a donor (allogeneic), to repair or replace damaged tissues. Examples include CAR-T cell therapy for cancer and CRISPR-based gene editing for rare genetic disorders (2).
2024 marked a significant year for gene therapy advancements. Several new therapies received FDA approval, further underscoring their transformative potential.
Gene Therapies Approved in 2024
The year 2024 saw the approval of several novel gene therapies, including groundbreaking treatments for genetic and rare diseases:
Roctavian (valoctocogene roxaparvovec) is indicated for the treatment of hemophilia A. In pivotal trials, it reduced annualized bleeding rates by over 80% and significantly decreased the need for factor VIII infusions. (3) As a one-time treatment, Roctavian challenges traditional chronic management models for hemophilia A.
Elevidys (delandistrogene moxeparvovec) is approved for Duchenne muscular dystrophy (DMD). Clinical data demonstrate that it improves motor function scores in pediatric patients, marking a major milestone in addressing this progressive condition. (4) Its approval underscores the growing success of gene therapies for pediatric rare diseases.
Upstaza (eladocagene exuparvovec) is used to treat aromatic L-amino acid decarboxylase (AADC) deficiency. Patients receiving Upstaza have shown remarkable improvements in motor milestones, with over 70% achieving head control, sitting, or walking within one year of treatment. (5) As the first gene therapy delivered directly to the brain, Upstaza sets a precedent for targeting central nervous system disorders.
These approvals reflect a rapidly expanding pipeline of innovative therapies that address critical unmet medical needs. However, their high costs continue to pose significant challenges for healthcare systems.
Clinical Data and Emerging Trends:
Clinical data support the efficacy of gene and cell therapies. For example, Zolgensma, a gene therapy for spinal muscular atrophy (SMA), demonstrated a 100% survival rate at 14 months in treated patients, compared to only 8% in untreated historical controls(6). Similarly, CAR-T therapies like axicabtagene ciloleucel (Yescarta) have shown durable remission rates of 68% in relapsed or refractory large B-cell lymphoma (7).
The 2024 approvals add to this growing evidence base. For example, Roctavian’s ability to sustain reduced bleeding episodes redefines hemophilia A management, while Elevidys offers a glimmer of hope for DMD patients, previously reliant on symptomatic care.
FDA Approved Gene and Cell Therapies by Therapy Categories
Gene and cell therapies span a diverse range of medical fields. Out of the 43 FDA-approved therapies, the majority fall under hematology (17) and oncology (12), reflecting a strong focus on treating blood disorders, regenerative medicine, and various cancers.
Gene and Cell Therapy by Therapy Categories
AWP Unit Price Distribution for FDA-Approved Gene & Cell Therapies
High-Cost Gene and Cell Therapies Employers Should Track
28% of approved therapies cost over $1 million per treatment, highlighting the financial risk.
The Expanding Gene & Cell Therapy Pipeline
Gene and cell therapies remain at the forefront of next-generation medicine, with over 2,968 therapies currently in development across oncology, rare diseases, and chronic conditions (1). These therapies hold the potential to cure or significantly alter the progression of previously untreatable diseases, but their high costs and long-term clinical impact present new challenges for employer-sponsored health plans.
Breakdown of the Gene & Cell Therapy Pipeline
2,068 Gene Therapies (including genetically modified cell therapies like CAR-T)
The majority are targeting oncology (leukemia, lymphoma, solid tumors) and rare genetic diseases such as spinal muscular atrophy, hemophilia, and sickle cell disease (1).
Ex vivo gene-modified cell therapies (like CAR-Ts) dominate the oncology space, while in vivo gene therapies are expanding into neurology, metabolic disorders, and cardiovascular diseases(1).
901 Non-Genetically Modified Cell Therapies
Many are focused on regenerative medicine, particularly for neurological disorders (Parkinson’s, ALS), musculoskeletal conditions, and autoimmune diseases (1).
Unlike gene-modified therapies, these treatments often involve stem cells or other cell-based interventions without genetic engineering, offering different safety and cost considerations (1).
What’s Next: RNA Therapies Emerging in Parallel
While gene and cell therapies continue to dominate the curative medicine pipeline, RNA-based therapies are now emerging in many of the same disease areas. With over 1,125 RNA therapies in development, including 344 mRNA therapies, 239 RNA interference (RNAi) therapies, and 269 antisense oligonucleotide (ASO) therapies, these treatments offer new approaches to many of the same high-cost diseases targeted by gene and cell therapies (2).
Key Strategies for Employers
To effectively navigate the integration of gene, cell therapies, and the RNA therapies, employers should consider the following strategies:
1. Understanding the Role of PBMs & Health Plans in CGT Coverage
Pharmacy benefit managers (PBMs) and health plans play a critical role in determining access, pricing, and reimbursement for CGTs. However, CGTs do not fit neatly into traditional pharmacy or medical benefit structures, leading to potential misalignments:
Coverage Design: Some health plans and PBMs treat CGTs as high-cost outliers, applying restrictive policies that delay or limit access. Employers should ask:
How does my PBM evaluate CGTs?
Are CGTs covered under my medical or pharmacy benefit?
What prior authorization requirements exist, and are they evidence-based?
Rebate Structures & Cost Transparency: Traditional PBM revenue models rely on rebates and spread pricing, which may not apply to CGTs. Employers should ask:
Is my PBM passing through the full negotiated price of CGTs, or is there an undisclosed margin?
Can my PBM provide a clear financial breakdown of how CGTs are priced and reimbursed?
Network Access & Site of Care Optimization: Not all hospitals or clinics are equipped to administer CGTs. Employers should ask:
Does my plan require CGTs to be administered at a specific center of excellence (COE)?
Can employees access out-of-network centers if better expertise is available?
Employers do not need to be adversarial with PBMs or health plans—but they do need to set clear expectations and ensure contracts reflect alignment with their cost and access priorities.
Employers should track CMS models and use them as benchmarking tools when negotiating payment structures for CGTs.
2. Leveraging Public & Private Payment Models for CGTs
The Centers for Medicare & Medicaid Services (CMS) is pioneering new approaches to CGT financing, and private employers can take valuable lessons from these initiatives:
Outcome-Based Contracts: CMS has negotiated with pharmaceutical manufacturers so that payment for CGTs is contingent on achieving clinical outcomes. Employers should explore similar risk-sharing agreements with payers and pharma companies.
Multi-Payer Risk Pooling: CMS enables states to negotiate together, spreading CGT costs across larger populations. Employers—especially self-insured groups—should consider coalition-based purchasing models to gain similar pricing leverage.
Centralized Price Negotiation: CMS acts as a single negotiator for CGTs, preventing price variability across states. Employers can push for direct contracts or work with coalitions to establish fair, predictable pricing.
3. Developing Smarter Utilization Management (UM) Strategies
While prior authorization and utilization management (UM) are necessary, generic cost-control measures won’t work for CGTs. Employers should ensure that UM policies support appropriate access while preventing waste and mismanagement.
Require Genetic Testing & Biomarker Validation
Ensure that employees receive CGTs only when medically necessary and clinically appropriate.
Prevent unnecessary spending by verifying that patients meet all clinical eligibility criteria.
Implement Post-Treatment Monitoring
Track long-term efficacy of CGTs in covered employees.
Link payment models to clinical outcomes rather than paying 100% upfront.
Ensure COE-Based Administration
Designate Centers of Excellence (COEs) to administer CGTs, ensuring consistent quality and cost efficiency.
Consider direct contracts with COEs to avoid unnecessary markups from third-party administrators.
Employers should proactively renegotiate stop-loss contracts to ensure CGTs are covered under sustainable financial terms.
Employers should not simply accept off-the-shelf PBM or insurer UM policies—instead, they should work to ensure policies are evidence-based and designed to balance cost control with timely access.
4. Structuring Financial Protection Against High-Cost Claims
CGTs present a unique financial risk to employers, especially self-insured plans. Traditional stop-loss insurance may not be structured to absorb CGT costs effectively, so employers must ensure their policies are adequately designed.
Ensure Stop-Loss Coverage for CGTs
Employers should review contracts to confirm CGTs are explicitly covered and not excluded under experimental therapy clauses.
Work with stop-loss carriers to implement multi-year reimbursement models, preventing large claims from distorting annual budgets.
Explore Alternative Risk-Sharing Approaches
Risk corridors with stop-loss insurers can help smooth costs over multiple years.
Consortium-based risk pooling allows employers to collectively mitigate exposure to one-time high-cost therapies.
Employers Must Take an Active Role in CGT Strategy
Gene and cell therapies challenge traditional benefits models, but employers who take a strategic, proactive approach can:
Ensure appropriate access for employees who need CGTs.
Implement cost-effective financing models that prevent budget volatility.
Hold PBMs and health plans accountable to align with employer priorities.
By asking the right questions, structuring contracts effectively, and leveraging both private and public models, employers can position themselves ahead of the curve in managing the next generation of high-cost, high-value therapies.
Why Partner with Axum Rx?
Your Expert Advisor in Gene & Cell Therapy
Navigating the complexities of gene and cell therapies (CGTs) requires strategic expertise. Axum Rx is here to help employers manage the evolving landscape of CGTs, offering:
Market Intelligence: Stay ahead of trends and pipeline developments.
Contract Negotiation: Secure value-based reimbursement agreements.
Utilization Management: Create responsible, evidence-based coverage policies.
Risk Mitigation: Integrate stop-loss coverage and financial risk-sharing models.
Partner with Axum Rx to ensure your health plan is cost-effective, future-proof, and ready for CGTs. Contact us today.
Contributions by Emily Yang, Pharm.D. Candidate 2025
References:
American Society of Gene and Cell Therapy (ASGCT). (2025). Gene and cell therapy clinical trials. Retrieved from https://www.asgct.org
Ma, X., Liu, Y., & Zhang, T. (2023). Advances in gene therapy for inherited diseases. Nature Reviews Genetics, 24(7), 490-502.
BioMarin Pharmaceutical Inc. (2024). Roctavian clinical data. Retrieved from https://www.biomarin.com
Sarepta Therapeutics. (2024). Elevidys: Duchenne muscular dystrophy therapy. Retrieved from https://www.sarepta.com
PTC Therapeutics. (2024). Upstaza clinical overview. Retrieved from https://www.ptcbio.com
Mendell, J. R., Al-Zaidy, S. A., & Shell, R. (2017). Single-dose gene-replacement therapy for SMA. New England Journal of Medicine, 377(18), 1713-1722.
Locke, F. L., Ghobadi, A., & Jacobson, C. A. (2022). Long-term outcomes of CAR-T cell therapy in large B-cell lymphoma. Blood, 140(5), 435-444.
Institute for Clinical and Economic Review (ICER). (2023). Value assessment of gene and cell therapies. Retrieved from https://icer.org
Micromedex Redbook. Comprehensive drug pricing database for gene and cell therapies. Available via subscription at https://www.ibm.com/products/micromedex-redbook.