One-Time vs. Curative Therapies: Changing Payer Economics

High-Cost Therapies Are Not New. The Economics Are Changing.

Payers have managed high-cost specialty therapies for years. Oncology biologics, complex autoimmune treatments, and rare disease drugs have long required careful financial planning and clinical oversight. What is changing is not the existence of expensive treatment, but the way those costs are incurred. A growing share of emerging therapies are designed to be administered once, and some carry the potential to be curative. That shift concentrates years of anticipated treatment cost into a single financial event, changing how payers, health plans, and plan sponsors forecast pharmacy spend, assess long-time value, and prepare for financial exposure.

One-Time and Curative Are Not the Same Thing

These two terms get used interchangeably, but they describe different characteristics of a therapy. A one-time therapy is defined by its dosing or how it is administered, typically a single infusion or procedure rather than ongoing dosing. A curative therapy, by contrast, is defined by its potential clinical outcome, the possibility that it resolves or substantially eliminates a disease long term. A therapy can be one without being curative, and potentially curative without being administered only once. Some one-time treatments eliminate the need for recurring dosing without curing the underlying condition. Some potentially curative therapies may still require ongoing monitoring, supportive care, or follow-up treatment. Getting this distinction right matters, because it changes how a payer should evaluate financial impact, expected outcomes, and long-term value.

Ultra-High-Cost Therapies Are Setting New Pricing Benchmarks

Cell and gene therapies illustrate this shift most visibly, though the broader trend extends beyond them. Recent one-time gene therapies for ultra-rare conditions have launched with multi-million-dollar price tags, including Hemgenix for hemophilia B and Lenmeldy for metachromatic leukodystrophy. Lenmeldy launched with a wholesale acquisition cost of $4.25 million for a one-time treatment, while Hemgenix carries a similarly significant upfront cost. Kresladi, a one-time gene therapy for severe leukocyte adhesion deficiency approved in early 2026, adds another example of the continued expansion of high-cost, one-time therapies into ultra-rare disease. Loargys, an enzyme replacement therapy approved around the same time for arginase 1 deficiency, illustrates the other side of this trend. It is an ongoing rather than one-time treatment, but its weight-based dosing can still push annual cost well into six or seven figures for some patients. These figures matter less as individual data points than as evidence of a broader direction. Payers are increasingly operating in an environment where a single approval can create substantial, concentrated upfront exposure—or, in the case of ongoing therapies, significant recurring expense—for a health plan or plan sponsor. The distinction matters because the timing, predictability, and duration of that spend can materially affect how a plan forecasts pharmacy costs and prepares for financial risk.

The Upfront Cost, Long-Term Value Tension

A potentially curative therapy may carry an extraordinary upfront cost while potentially reducing or eliminating years of future pharmacy and medical spending, including hospitalizations, ongoing medications, and disease management. That creates a fundamental tension between when the payer incurs the cost and when the potential value is realized. The payer covering the treatment today may not retain that member long enough to see the full benefit, particularly in employer-sponsored coverage, where member turnover can shift future costs and savings across plans. Cost alone does not tell the full economic story, but neither can projected long-term savings be treated as a certainty. Outcomes for many of these therapies are still being established in real-world settings, creating uncertainty around the magnitude and duration of clinical benefit, future medical and pharmacy costs, and the resulting financial value to the payer. That makes the evaluation more complex and puts greater importance on understanding both the immediate budget impact and the assumptions behind projected long-term savings.

What This Means for Pharmacy Spend Forecasting

Traditional financial forecasting models has largely been built around recurring, relatively predictable costs. A treatment landscape shaped by large, concentrated, one-time financial exposure requires a different approach. Payers need visibility into which therapies are approaching approval, the populations they may affect, how they may be administered, and the potential financial exposure they could create, well before a claim arrives. That means pipeline monitoring becomes an essential pharmacy benefit planning function, not simply a clinical one. Waiting until a therapy is approved to start modeling its impact leaves plan sponsors reacting to costs that could have been anticipated and planned for earlier.

Proactive Planning Requires Pipeline Visibility

Effective planning connects several capabilities.

• Tracking the emerging therapy pipeline.
• Modeling potential financial exposure against the specific covered populations.
• Evaluating the long-term clinical and economic value a therapy may deliver over time.

None of this requires waiting for a specific approval date. It requires treating the pipeline as a current planning input rather than a future contingency. Organizations that build this visibility earlier are better positioned to evaluate contracting options, structure risk arrangements, forecast pharmacy spend, and prepare member communication strategies before a high-cost event becomes urgent.

The Limits of Financial Risk Management

Stop-loss arrangements, reinsurance, and outcomes-based contracts all have a role in cost containment for this kind of concentrated, high-risk financial exposure, and many payers are actively evaluating how these structures apply to one-time and potentially curative therapies specifically. But financing mechanisms alone do not solve the underlying planning challenge. A payer with the right risk arrangement in place, but no visibility into which therapies are approaching the market, which populations may be affected, or what the potential financial exposure could be, is still managing the risk reactively. The effectiveness of a financial risk strategy depends in part on the forecasting and planning that precede it.

What Payers and Plan Sponsors Should Do Now

Three priorities matter most right now.

• Pipeline monitoring, so that emerging one-time and potentially curative therapies are identified well before approval and incorporated into planning.
• Financial forecasting, so that potential exposure is modeled against actual covered population data rather than broad industry averages.
• Long-term value evaluation, so that upfront cost gets weighed against realistic, evidence-based projections of potential future pharmacy and medical cost offsets, not assumed savings.

None of this requires waiting for a specific approval before taking action. It requires organizational commitment to treating this shift in treatment economics as a current planning priority rather than a future financial risk.

How AscellaOne Supports Proactive Pharmacy Spend Planning

As one-time and potentially curative therapies continue to enter the market, organizations that can see emerging therapies and model their potential financial impact before a claim arrives are better positioned to plan ahead. Building that capability internally requires specialty pharmacy expertise, integrated data, and the ability to translate emerging therapies into population-specific financial exposure. AscellaOne is a modular pharmacy benefits enablement platform that brings pharmacy access, financial optimization, data, and specialty pharmacy expertise together in a single operating model, without requiring health plans or plan sponsors to build that infrastructure themselves. The platform connects pharmacy benefit data with specialty pharmacy expertise so that financial forecasting and clinical evaluation are informed by a shared view of the pharmacy benefit. This gives payers earlier visibility into emerging exposure and greater ability to forecast spend, evaluate options, and plan for high-cost therapies before they become urgent financial events. Organizations looking to strengthen their approach to high-cost therapy planning can explore AscellaOne as a pharmacy benefits enablement partner. Learn more about AscellaHealth’s modular pharmacy benefits platform and how it supports proactive planning for the next generation of high-cost treatment. The platform is built around one simple idea. One Modular Platform. Total Pharmacy Benefits Control.

Frequently Asked Questions About One-Time and Curative Therapy Economics

What is the difference between a one-time therapy and a curative therapy?

A one-time therapy is defined by its dosing or how it is administered, typically a single infusion or procedure instead of ongoing dosing. A curative therapy is defined by its potential clinical outcome, such as the possibility of achieving a lasting resolution of a disease or condition. A therapy can be one without being the other, so payers need to evaluate these characteristics separately rather than assume they always occur together.

Why are payers concerned about one-time and potentially curative therapies specifically?

These therapies concentrate years of anticipated treatment cost into a single financial event rather than spreading those costs across recurring claims. That shift changes how payers need to forecast pharmacy spend, assess near-term budget impact and longer-term financial exposure, and prepare for high-cost events. Managing expensive therapies is not new, but the timing and concentration of the financial exposure can create a different planning challenge.

How much do recent one-time gene therapies cost?

Recent one-time gene therapies for ultra-rare conditions have launched with multi-million-dollar price tags. For example, Hemgenix, a one-time gene therapy for hemophilia B, launched in the U.S. with a wholesale acquisition cost of approximately $3.5 million, while Lenmeldy, a one-time gene therapy for metachromatic leukodystrophy, launched with a wholesale acquisition cost of $4.25 million. Newer entrants, including Kresladi for severe leukocyte adhesion deficiency, are expected to launch in a similar range. These are manufacturer list prices and do not necessarily represent the amount ultimately paid by a health plan. Ongoing, non-one-time therapies for ultra-rare conditions can carry substantial annual cost as well, as with Loargys for arginase 1 deficiency. These figures illustrate a broader pricing trend across the category rather than a fixed benchmark, since pricing continues to evolve as new therapies reach the market.

Does a high upfront cost mean a therapy is poor value?

Not necessarily. A high upfront cost needs to be weighed against the potential to avoid years of future pharmacy and medical spending, including hospitalizations and ongoing disease management. That said, long-term savings from a potentially curative therapy are not guaranteed, which is why proactive evaluation matters more than assuming either outcome.

What is the financial timing problem with potentially curative therapies?

The payer incurs the cost of a potentially curative therapy immediately, but the value it may unfold over years or even decades. A payer may not retain a given member long enough to realize the full benefit, particularly in employer-sponsored plans where membership turnover is common. This mismatch between when cost occurs and when value is realized is a defining financial challenge for these therapies.

How should payers approach financial forecasting for these therapies?

Payers should build pipeline monitoring into financial forecasting rather than waiting for commercial approval to begin modeling impact. That means tracking therapies in later-stage development, estimating potential exposure against actual covered population data, and revisiting those models as the pipeline evolves.

Is this primarily a cell and gene therapy issue?

Cell and gene therapies are the clearest current example of this shift, but the underlying issue is broader. Any treatment modality that concentrates a significant cost into a single administration event raises the same forecasting and planning questions, regardless of the specific therapeutic category involved.

What role do reinsurance and outcomes-based contracts play?

Stop-loss arrangements, reinsurance, and outcomes-based contracts help distribute or manage the financial risk associated with high-cost therapies. These structures are a meaningful part of a broader strategy, but they work best when paired with proactive pipeline visibility rather than serving as a standalone solution.

What should self-insured employers and smaller health plans do first?

Self-insured employers and smaller health plans should start with pipeline monitoring and financial modeling against their own covered population, since they typically carry this risk without the scale to absorb financial variability as easily as larger plans. Partnering with a pharmacy benefits platform that already has this infrastructure can significantly shorten the path considerably.