The Future is Now: RNA Therapies and Your Benefit Strategy

RNA-based therapies are at the forefront of precision medicine, offering novel treatments for a wide range of diseases, including rare genetic disorders, oncology, and chronic conditions. As of January 31, 2024, there are 21 FDA-approved RNA-based therapies, with at least 131 therapies in clinical trials and many more in pre-clinical development(1). The broader pipeline now exceeds 1,125 RNA therapies, signaling rapid innovation in this space (2).

These therapies span 15 different therapeutic areas, many addressing conditions with limited or no existing treatment options (3). Some RNA-based therapies are designed for infrequent dosing schedules, such as once or twice per year, which could improve patient compliance and long-term outcomes (4). While majority of the pipeline remains in early-stage development (Phase I or II), 29 therapies have reached late-stage clinical trials, highlighting the strong potential for new FDA approvals in the coming years (5).

Employers must pay close attention to the rise of RNA-based therapies, as their high costs, recurring treatment schedules, and expanding indications will have a profound impact on healthcare spending. With more approvals on the horizon, self-funded employers must proactively assess coverage strategies, cost-management approaches, and long-term financial implications. This report will provide an overview of the RNA therapy landscape and key considerations to help employers navigate this evolving space effectively.

Key RNA Therapy Categories and Their Impact: Understanding the Landscape

mRNA Therapies (344 in development) (3): These therapies deliver a specific mRNA sequence into cells, instructing the ribosomes to produce a desired protein. Examples include Moderna’s mRESVIA (RSV vaccine)(5), but the future holds promise for applications in oncology, metabolic disorders, and rare genetic diseases(2). Employers must stay informed about these rapidly developing treatments and their potential budget impact.  

RNA Interference (RNAi) Therapies (239 in development) (3): These therapies use siRNAs to silence specific genes, reducing the production of disease-causing proteins. Alnylam’s Onpattro for transthyretin amyloidosis is one example (2). Because these therapies often target rare diseases, employers should be prepared for potentially significant claims from a small number of individuals.  

Antisense Oligonucleotide (ASO) Therapies (269 in development)(3): These therapies use ASOs to bind to target RNA sequences, influencing protein production. Ionis Pharmaceuticals’ Spinraza for spinal muscular atrophy is a prominent example (2). The varying dosing regimens (one-time vs. chronic) of ASO therapies require careful long-term financial planning (5).  

Know the difference:

• Gene therapy: Permanent change to DNA.  .

• Cell therapy: Administration of living cells for therapeutic benefit

• RNA therapy: Transient modulation of gene expression at the RNA level

Key Differences Between RNA Therapies and Gene & Cell Therapies

RNA therapies differ from gene and cell therapies in their mechanism, duration of effect, and treatment approach. While gene and cell therapies often provide long-term or curative outcomes by permanently altering genetic material or replacing dysfunctional cells, RNA-based treatments require ongoing administration to maintain their effects. This distinction has significant implications for treatment planning, cost, and patient management.

• Treatment Approach

  • Gene and cell therapies offer durable solutions by modifying DNA or replacing cells.

  • RNA therapies temporarily alter gene expression at the RNA level and must be continuously administered.

• Duration of Effect

  • Gene therapies (e.g., viral vector-based treatments) and cell therapies (e.g., CAR-T therapy) can provide long-term or curative results.

  • RNA therapies degrade over time, requiring repeat dosing to sustain their therapeutic impact.

• Key Advantage of RNA Therapies

  • RNA therapies provide a targeted and reversible approach without permanently altering DNA.

  • However, their reliance on ongoing treatment differentiates them from curative gene and cell therapies.

By understanding these differences, employers and healthcare decision-makers can better assess the role of RNA therapies in managing chronic and rare diseases.

Market Growth & Financial Implications: A Looming Challenge for Employers

The global RNA-based therapeutic market is projected to grow significantly in the coming years. According to a report published on February 10, 2025, the market size is estimated at approximately $9.46 billion in 2025 and is expected to reach around $40.81 billion by 2034, reflecting a compound annual growth rate (CAGR) of 17.64% during this period (8). This driven by advancements in mRNA, RNA interference (RNAi), and antisense oligonucleotide (ASO) therapies (6). These therapies are increasingly targeting high-cost conditions like oncology, neurodegenerative diseases, and rare genetic disorders, many with price tags exceeding $500,000 per patient per year (2).

Consider the financial impact:

• Patisiran (Onpattro) for hereditary transthyretin-mediated amyloidosis (hATTR): Approximately $575,000 annually for a patient weighing 75.6 kg.

• Givosiran (Givlaari) for acute hepatic porphyria (AHP): Approximately $575,000 annually for a patient weighing 75.6 kg.

• Lumasiran (Oxlumo) for primary hyperoxaluria type 1 (PH1): Approximately $495,000 annually.

While these are just a few examples, the trend is clear—RNA therapies represent a significant financial challenge for employers.

The financial implications for employer-sponsored health plans are unprecedented, rivaling or even surpassing those of gene and cell therapies (1). Take, for example, Viltolarsen (Viltepso), an antisense oligonucleotide (ASO) therapy for Duchenne muscular dystrophy (DMD). Based on FDA-approved dosing guidelines (80 mg/kg weekly) and an average wholesale price (AWP) of approximately $1,690 per 250 mg vial, the annual treatment cost for a single 70 kg (154 lbs) patient can exceed $2 million. While negotiated discounts and rebates may lower the final price, the financial exposure remains substantial (5).

Now, scale this cost across a population:

• If just 10 employees or dependents require a high-cost RNA therapy like Viltepso, employer-sponsored plans could face over $20 million in annual claims (7).

• Even more common RNA-based treatments, such as Spinraza ($750,000 in the first year, then $375,000 annually) or Onpattro ($575,000 annually), present recurring financial burdens (3).

• Unlike one-time gene therapies, RNA-based treatments typically require lifelong administration, meaning that costs will compound each year, creating long-term budgetary strain (2).

Employer Challenges and Strategies: A Proactive Approach

The rise of RNA therapies presents a complex challenge for employers: balancing the promise of life-changing treatments with the very real financial implications. A proactive, strategic approach is essential. Here's a deeper dive into the key areas employers must address, from the perspective of a specialty drug management expert:

Cost Management & Risk Mitigation: With RNA therapies now rivaling gene therapies in cost—employers must proactively manage financial exposure. This requires a multi-pronged approach:

Strengthened Stop-Loss Protections: Standard stop-loss policies may not adequately cover the exorbitant costs of some RNA therapies. Employers should negotiate specific carve-outs or higher thresholds for these treatments to protect against catastrophic claims. Don't assume your current policy is sufficient.

Alternative Payment Models: Traditional fee-for-service models are ill-suited for these high-cost, high-value therapies. Explore value-based contracts that tie reimbursement to real-world patient outcomes. Negotiate hard on these contracts; your leverage is your employee population.

Integration with PBMs & Health Plans: Employers must demand transparency and collaboration from PBMs and health plans regarding RNA therapies. This is where expertise is most needed:

Clear Pricing and Rebate Structures: Demand full transparency on drug pricing, discounts, and rebates. PBMs often obscure these details, making it difficult for employers to assess true costs. Negotiate for "pass-through" pricing models where you directly benefit from manufacturer rebates.

Active Review of PBM Formularies: Don't passively accept PBM formularies. Actively review them to ensure appropriate access to medically necessary RNA therapies. Some PBMs may restrict access due to cost concerns. Advocate for broader formulary inclusion and challenge restrictive policies.

Innovative Contracting Approaches: Explore risk-sharing arrangements with PBMs and health plans. These contracts can align incentives and encourage better management of healthcare spending. For example, tie a portion of PBM compensation to achieving specific cost or outcome targets.

Utilization Management & Clinical Oversight: Effective oversight is crucial to ensure appropriate use of these therapies and prevent misuse. This requires:

Genetic Testing and Biomarker Validation: Require robust pre-authorization processes, including genetic testing and biomarker validation, to confirm patient eligibility and ensure these therapies are used only when clinically appropriate. This protects against off-label use and inappropriate prescribing.

Centers of Excellence (COEs): Consider restricting administration to specialized Centers of Excellence. COEs have the expertise and infrastructure to deliver these complex therapies safely and effectively, potentially improving patient outcomes and reducing complications. Negotiate favorable rates with COEs.

Long-Term Cost Projections: Understanding the long-term costs associated with different RNA therapies, including potential repeat dosing or ongoing monitoring, is essential for financial planning. Work with actuaries to model these costs and incorporate them into your long-term budget forecasts. Don't get caught off guard by recurring expenses.

Ethical Considerations: Balancing access to innovative treatments with cost management is a complex ethical challenge. Develop clear ethical guidelines for coverage decisions, ensuring transparency and fairness.

Staying Informed: The field is rapidly evolving. Employers must stay up-to-date on new developments, clinical trials, and FDA approvals. Subscribe to industry publications, attend conferences, and engage with experts in the field. Knowledge is power in this rapidly changing landscape.

The Path Forward

RNA therapies represent a new era in medicine, offering unprecedented opportunities to improve patient lives. By proactively planning and implementing a strategic approach, employers can ensure their employees have access to these life-changing treatments while effectively managing the associated financial implications. This requires a commitment to staying informed, collaborating with key stakeholders, and embracing innovative solutions. The future of healthcare is here, and it’s our responsibility to navigate it strategically.

Why Partner with Axum Rx?

Your Expert Advisor in RNA Therapy

Navigating the complexities of RNA therapies requires strategic expertise. Axum Rx is here to help employers manage the evolving landscape of RNA therapies, 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 RNA therapies. Contact us today.

Contributions by Emily Yang, Pharm.D. Candidate 2025