Optimizing the management of inherited blood disorders in a changing market: Findings from the AMCP Market Insights Program

Abstract

In this market insights program, AMCP brought together a panel of experts representing various stakeholders: national and regional health plans, integrated health care systems, employer benefits groups, clinical experts, the Centers for Disease Control and Prevention, and patient advocacy organizations. The objectives were to gain insights into the current and evolving treatments in hemophilia, sickle cell disease, and β-thalassemia; measure the effects of recently approved therapies on clinicians, payers, and patients; recognize emerging trends within the stop-loss market; address potential issues and obstacles related to monitoring and reporting outcomes; and identify concerns associated with both existing and emerging contracting and reimbursement models. This article aims to summarize expert perspectives on health care system challenges and strategies concerning the management of inherited blood disorders and to advance managed care professionals’ understanding of their role in supporting care for these patients. The experts emphasized that when shaping coverage policies, a patient-centered approach is crucial, focusing on preserving organ function to maintain eligibility for future gene therapies among individuals with inherited blood disorders. These strategies, including benefit design modifications, specialized provider networks, and centralized mechanisms like registries, are vital for evaluating effectiveness, facilitating decision-making, and managing costs and risks associated with new and emerging treatment options for inherited blood disorders.

Plain language summary

Health care leaders will need plans for handling new treatments for inherited blood disorders. This might mean changing benefits for treatments to make sure patients can get gene therapy. People with inherited blood disorders are better off when they get care from different types of health care providers. Using systems like registries to keep track of how treatments affect health and business agreements is important. These kinds of steps are important for figuring out how well new treatments work over a long time, making decisions, and managing costs for inherited blood disorders.

Implications for managed care pharmacy

Managed care organizations need strategies for managing innovative treatments for inherited blood disorders. This may include modifying benefit designs to cover disease-modifying treatments to ensure patients are eligible for gene therapy, establishing networks of specialized health care providers to facilitate multidisciplinary care, and implementing centralized mechanisms like registries for monitoring health outcomes and risk-based agreements. These strategies are crucial for evaluating long-term effectiveness and safety, ongoing decision-making, and cost management of inherited blood disorders.

Single-gene (monogenic) blood disorders that disrupt the formation, architecture, or functionality of blood cells or clotting factors encompass a broad spectrum of conditions, including coagulation disorders (eg, hemophilia) and hemoglobinopathies (eg, sickle cell disease and thalassemia).

Hemophilia A and B

Hemophilia A and B are characterized by an increased susceptibility to bleeding due to inherited deficiencies in factor VIII and factor IX, respectively, which disrupt the blood clotting process. Both conditions exhibit X-linked recessive inheritance patterns and predominantly affect male individuals.¹ There are approximately 20,000 people in the United States with hemophilia.² Patients with both hemophilia A and B, particularly those with severe disease, are at risk for life-threatening bleeding, including intracranial bleeding, but bleeding into a joint or muscle is more common and leads to substantial disability from pain and loss of mobility. For patients with severe hemophilia, taking the prescribed treatment regularly before a bleed occurs can lower the frequency of joint bleeds and prevent joint damage.³

Over the years, extensive clinical research and drug development have benefited patients with hemophilia, offering treatment options that enable a near-normal life expectancy with minimal joint complications.¹ To minimize bleeding risk, individuals with severe hemophilia often receive intravenous factor concentrate therapy multiple times weekly. Several factor products are available, some with modifications to prolong their effectiveness. The goal of sustained normal hemostasis is not achieved by any of the current treatment options. The typical yearly expenditure for clotting factor therapies in an individual with severe hemophilia ranges from $300,000 to $600,000.^4,5 However, individuals with an inhibitor (an immune reaction to replacement clotting factor) often incur expenses exceeding $1 million annually.⁴ Many patients with hemophilia A now use a nonfactor replacement therapy, emicizumab, a monoclonal antibody that following a loading dose can be administered every week, every 2 weeks, or monthly by subcutaneous injection, for prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients ages newborn and older with or without factor VIII inhibitors.⁶ However, no similar prophylaxis is currently US Food and Drug Administration (FDA) approved for patients with hemophilia B.

Sickle Cell Disease

Sickle cell disease (SCD) is the most common inherited blood disorder in the United States and affects an estimated 100,000-120,000 Americans.^7-9 The estimated cost of care for SCD in the United States is approximately $1.1 billion per year, the majority of which is paid for through public insurance programs like Medicaid and Medicare.¹⁰ Patients with SCD with recurrent vaso-occlusive crisis (VOCs) incur higher annual ($67,282 vs $4,134) and lifetime ($3.8 million vs $229,000 over 50 years) health care costs.¹¹ Clinically, SCD can cause severe pain associated with VOCs, splenic sequestration, acute chest syndrome, bacterial sepsis, ischemic strokes, and silent cerebral infarcts. Recurrent VOCs lead to frequent health care visits and interference with daily functioning and impact the quality of life for individuals with SCD. Pain is the most common complication of SCD and the top reason people with SCD go to the emergency department or hospital. People with SCD typically experience premature mortality, with an average lifespan (age at death) of 39 years.⁸ However, there is also an observable trend toward increased longevity over time among those with SCD.⁸

The poor health outcomes in SCD are influenced by limited access to quality comprehensive care and a stigma that contributes to negative health care interactions and decreased physiological and psychological well-being.¹² Disease-modifying treatments, such as hydroxyurea, are often underprescribed to patients who may need them most.^13,14 Adverse perceptions regarding hydroxyurea, which encompass concerns about potential carcinogenicity and negative effects on fertility, as well as various obstacles to its use, act as deterrents to patients adhering to this medication.¹⁵ The renewed importance of the proper use of disease-modifying therapies in SCD stems from their role in preparing patients for the potential of gene therapy. Disease-modifying therapies are specifically designed to alleviate pain crises, minimize organ damage, and improve overall health. Adherence to these therapies limits organ damage, positioning patients as more suitable candidates for gene therapy, which is a treatment that offers the promise of a potential cure.

“The longer the patients live with the disease, the more you have chronic complications that can evolve and lead to organ dysfunction. That’s why it is really important to get patients on disease-modifying therapy and potentially looking at cure or with gene therapy.” – Hematologist, Market Insights presenter and panelist

Thalassemia

Thalassemia refers to a spectrum of diseases characterized by reduced or absent production of one or more globin chains. α-Thalassemia and β-thalassemia are inherited hemoglobin disorders characterized by reduced production of either the α- or β-globin chain, resulting in an imbalance in their ratios. β-Thalassemia is caused by variants in the hemoglobin β locus that lead to impaired production of β-globin chains and an excess of α or α-type chains. This imbalance contributes to problems in red blood cell maturation, ultimately giving rise to ineffective erythropoiesis, hemolytic anemia, and iron overload.

In the United States, thalassemia predominantly occurs in individuals with ancestral ties to Asia, India, and the Middle East.¹⁶ The most severe form of the disease is transfusion-dependent β-thalassemia, which has a lifetime estimated cost of $5.4 million per patient.¹⁷ Transfusion-dependent β-thalassemia requires frequent red blood cell transfusions and daily iron chelation therapy, which can impact quality of life, work productivity, and the amount of time needed to manage the disease.¹⁸

Given the monogenetic foundation of these inherited blood disorders, gene therapies have long been regarded as the most promising avenue for achieving long-term impact on disease burden. With the recent FDA approvals of novel treatment options across inherited blood disorders, managed care and payer professionals are now engaged in efforts to ensure appropriate and cost-effective use of these novel treatments.

Changing Market

Building upon the insights derived from a Nexus 2022 multistakeholder roundtable, AMCP organized a second Market Insights panel in the fall of 2023 comprising experts from national and regional health plans, integrated health care systems, employer benefits groups, clinical experts, the Centers for Disease Control and Prevention (CDC), and patient advocacy organizations. Health plans and patient advocacy organizations constituted 60% of the panel, with other experts being generally evenly represented. This panel’s objectives were to discuss the results of AMCP’s landscape research, gather perspectives on the impact of newly approved and emerging therapies, examine the implications of trends in stop-loss policies, and assess the opportunities with different contracting and reimbursement models.

As monogenic disorders with well-understood genetics, these inherited blood disorders are ideal disorders for implementing gene therapies. Indeed, recent approvals of gene therapy products in hemophilia and in β-thalassemia have the potential to shift the treatment paradigm. Additionally, the treatment of SCD is set to be transformed with the US approval of gene therapies. The panelists were provided with an overview of newly approved and emerging therapies for the treatment of inherited blood disorders as clinical background to inform their discussions, and they introduced an issue related to drug shortages currently impacting patients.

Valoctocogene roxaparvovec is an adeno-associated virus serotype 5–mediated gene therapy for hemophilia A. It is a one-time infusion of a B-domain-deleted factor VIII gene to cells in the liver, resulting in production of an active variant of factor VIII. At the time of the second Market Insights panel, available study data showed that the durability of factor VIII activity and bleeding reduction from valoctocogene roxaparvovec at least 2 years after the gene transfer was similar to that reported from epidemiologic data for people with mild to moderate hemophilia A.^19,20

Etranacogene dezaparvovec is an adeno-associated virus serotype 5–mediated gene therapy for hemophilia B. It involves a single infusion of the Padua variant of the factor IX gene into liver cells, leading to the production of an active form of factor IX. Patients who received etranacogene dezaparvovec experienced an 80% decrease in treated joint bleeds and saw similar reductions in other bleeding incidents when compared with their bleeding rates while on factor prophylaxis before undergoing gene therapy.²⁰ At the time of the second panel meeting, available data from the initial 18 months following therapy with etranacogene dezaparvovec showed that none of the treated patients required a return to factor prophylaxis.²¹

Betibeglogene autotemcel is a gene therapy indicated for patients with transfusion-dependent β-thalassemia. It is manufactured ex vivo using an individual’s own hematopoietic stem cells, and then a lentiviral vector (BB305) is used to add functional copies of the β-globin gene to patients’ stem cells.¹⁵ The modified stem cells are then infused intravenously back into the individual following conditioning chemotherapy. Transfusion independence was achieved in 89% of the patients who received betibeglogene autotemcel.²²

Lovotibeglogene autotemcel is a gene therapy for SCD. Lovotibeglogene autotemcel works by using a modified virus (lentivirus vector) to insert a functioning version of the HBB gene into the patient’s own stem cells. Exagamglogene autotemcel is a gene therapy used for the treatment of SCD and transfusion-dependent β-thalassemia. It uses a gene editing approach using CRISPR-based technology to increase the amount of fetal hemoglobin in red blood cells by deleting a portion of the BC11A gene.²³

Drug shortages are also changing the treatment landscape for some patients with hemophilia. Panelists raised the topic around the impact of Ferring Pharmaceuticals’ suspended production of desmopressin nasal spray, which helps increase blood clotting in people with type 1 von Willebrand disease and hemophilia A. The production was suspended because of a packaging seal problem that led to evaporation and potentially dangerously high concentrations of the active ingredient, desmopressin.²⁴ Many patients who previously used desmopressin nasal spray have been prescribed clotting factor instead, which is more costly and requires intravenous infusion. To bridge the gap, the Hemophilia Alliance, a trade association for many of the federally funded hemophilia treatment centers, turned to STAQ Pharma, a 503B outsourcing facility, which was able to put desmopressin into production in 2021. Many of the payer panelists were unaware of the availability of the STAQ version of desmopressin, and the patient advocates described challenges in getting payers to reimburse for this product. Ferring announced intentions to resume production, but patient advocates’ confidence is low given that nearly 3 years have elapsed since production was suspended.

Centers of Excellence

The panelists were provided with an overview of hemophilia treatment centers (HTCs), which are recognized by the Health Resources and Services Administration and the CDC as centers of excellence (COEs) in delivering care of individuals with rare and benign bleeding and clotting disorders, to support discussions around opportunities for different contracting and reimbursement models. HTCs follow a medical home model of care, using a collaborative team approach that includes physicians, nurses, pharmacists, physical therapists, social workers, and other health care professionals with specialized expertise in the treatment of hemophilia.¹ HTCs primarily focus on the care and treatment of individuals with bleeding and clotting disorders, particularly hemophilia. Many HTCs also provide services to individuals with other rare bleeding disorders. However, the specific services and capabilities may vary from one HTC to another. Research conducted by the CDC has demonstrated that HTC patients experience significantly lower mortality and hospitalization rates, with a 40% reduction compared with individuals not receiving care at HTCs, even though HTCs tend to serve more severely affected patients.²⁵

“One of the things that we proposed doing would be to have a requirement that patients being treated for hemophilia have at least an annual visit with an HTC… Because when you’re dealing with any disease that has so much complexity, it’s a very delicate balance. If you can manage to establish and maintain that balance, patients will experience better overall health, and in the long run, you should save money.” – Payer, Market Insights panelist

Whereas patients with hemophilia have the benefits of expert care and well-coordinated services offered by HTCs, there are fewer specialized treatment centers for individuals with SCD and thalassemia in the United States. Furthermore, the extending life expectancy of those with inherited hemoglobin disorders underscores the critical need for enhanced support during the transition of care from pediatric to adult health care providers. Patients with SCD often receive care from general practitioners, emergency department physicians, and hospitalists, who may have limited expertise in managing their specific condition and limited knowledge of recommended treatments.

“I think one of the things is that part of the reason these medications aren’t being prescribed is because patients aren’t being seen by the appropriate specialists to get to those drugs.” – Patient Representative, Market Insights panelist

Health Care Landscape Research

AMCP conducted 6 in-depth expert interviews with managed care and oncology professionals representing more than 77 million covered lives and conducted an online survey of COEs across 18 states, who provide care to an estimated 13,000 patients with blood disorders (survey available in Supplementary Materials ^{(188.1KB, pdf)} , available in online article). The interviews and survey were structured to build on insights from the 2022 AMCP Market Insights findings on optimizing the management of inherited blood disorders.²⁶ Panelists reviewed and discussed the landscape insights.

INSIGHTS FROM MANAGED CARE AND PAYER INTERVIEWS

Payers are taking a pragmatic approach to covering current and emerging treatments, including gene therapies, by evaluating the latest scientific evidence and clinical trials to determine coverage criteria (Table 1). Many payers state they look to clinical trial inclusion/exclusion criteria and FDA labels to inform coverage policies for inherited blood disorder treatments. Payers are also taking into consideration the recommendations from professional medical societies and expert consensus statements.

TABLE 1.

Managed Care Perspectives From Market Insights Program In-Depth Interviews on Gene Therapy Clinical Appropriateness and Possible Value-Based Contracting Outcomes

Hemophilia

Gene therapy is generally considered clinically appropriate for individuals with severe or moderate hemophilia who have experienced frequent bleeding episodes and have not responded well to standard treatments, and coverage will likely align with the treatment on the FDA label. Value-based contracting outcomes of interest include reducing or eliminating the need for regular clotting factor infusions and reducing the number of bleeds.

Sickle cell disease

Gene therapy will likely be appropriate (pending FDA approvals) for all individuals with sickle cell disease, particularly those with severe symptoms and frequent complications. Payers are interested in seeing outcomes such as reducing the frequency and severity of pain crises, organ damage, and hospitalizations as potential value-based measures.

β-Thalassemia

Gene therapy is generally considered for individuals with severe β-thalassemia who require regular blood transfusions or experience complications associated with the disease. Payers are interested in reducing or eliminating the need for regular transfusions and improving hemoglobin production.

FDA = US Food and Drug Administration.

“When it comes to clinical trial exclusions, my assumption is that pharma does not think it is going to work in those patients…so why should we be paying for that?” – Payer, Market Insights panelist

Payer Challenges. Payers acknowledge that patients with inherited blood disorders who are enrolled in different insurance plans have varying access to treatments. The Centers for Medicare & Medicaid Services (CMS) rules are significant in shaping coverage polices through their national and local coverage determinations. However, there is increasing pressure from self-insured employers to control costs, and some are excluding existing high-cost therapies as well as emerging gene therapies from coverage. High-deductible health plans are seen as a factor directly impacting equity and affordability for patients with inherited blood disorders.

“Stop-loss insurance follows the plan document. So whatever exclusions are on the plan document, that’s excluded from stop-loss. It’s one of the things I talk to our clients about when considering excluding gene therapy… if you exclude it and you have a stop-loss policy, then if you make an exception to cover a gene therapy, you are not protected by the stop-loss.” – Employee Benefit Expert

Treatments. The advent of multiple therapies with million-dollar price tags raised concerns with expert interviewees and the panelists around how best to provide equitable access in an environment of limited health care resources. Additionally, several payers expressed concern around the broader issue of unsustainability of current health care financing owing to increasing insurance premiums and use of glucagon-like peptide-1 inhibitors.

Every payer expressed some level of concern related to the financial risk and impact of new therapies for inherited blood disorders. Among the major concerns identified by the payer panelists is the need for appropriate balance between the urgency to respond to unmet patient needs with the uncertainty of new therapies, and concern around treatment durability, affordability, and variation in coverage that could affect patient access. The panelists also acknowledged that policy, regulations, and business operations will need to evolve to enable access to emerging therapies.

The expected adoption for gene therapies in patients with SCD was misaligned across patients, clinicians, and payers. Payer panelists acknowledged the unmet patient needs and lack of disease-modifying treatments as factors influencing the early adoption of SCD gene therapies, whereas patients and clinicians expressed hesitation given these therapies are based on an autologous transplantation of hematopoietic stem and progenitor cells, which requires that the patient has sufficient organ function to undergo the chemotherapy preparation and has access to a qualified transplant center. Patient representatives reported that they fear many patients with SCD will have too much organ damage to be candidates for gene therapy, especially if appropriate use of disease-modifying therapies is or has been lacking. These factors are anticipated to lower the number of patients with SCD who are eligible to receive gene therapy.

Both the patient representatives and clinician panelists highlighted the value of current and emerging clotting factor treatments for patients with hemophilia, which may impact the enthusiasm for gene therapy in this population of patients as well. Payers report that they will likely be covering the recently approved β-thalassemia and hemophilia gene therapies based on the FDA-approved indications and would not likely apply more stringent coverage criteria. Although the new and potentially curative therapies for inherited blood disorders bring the promise of considerable lifetime benefit, the payer panelists reiterated their concerns regarding longer-term safety and the durability of benefits. Additionally, some payers described interest in implementing once-in-a-lifetime gene therapy policies, which may also slow the adoption of gene therapies if patients and clinicians choose to wait for more data or approval of other agents in the pipeline.

INSIGHTS FROM THE BLEEDING DISORDER COE NATIONAL SURVEY

Twenty-four centers across 18 states participated in the bleeding disorder COE survey. Four kinds of COEs were surveyed and represented (university-based, 41%; standalone facilities, 26%; integrated delivery system, 26%; and children’s hospital, 15%), with the majority (89%) of COEs reporting they treat patients with hemophilia and von Willebrand disease, whereas significantly less also treat SCD (7%) and β-thalassemia (4%).

All survey respondents (N = 28, 100%) reported that they must customize treatment decisions based on both the patient’s clinical needs and the patient’s health insurance plan requirements. Survey respondents were asked to select the most common access challenges patients experience because of their health insurance coverage from a list of 4 options, where more than one option could be selected. A majority (88%) of respondents reported patients face difficulties in gaining approval from their health insurance providers for the therapies prescribed to manage their bleeding disorder. Nearly half (41%) cited patient challenges related to accessing their preferred health care providers. Similarly, 41% of respondents reported that patients face obstacles in accessing mental health services, and 41% selected difficulty in accessing pain management services. Pain management is crucial for individuals with bleeding disorders, as they often experience chronic pain as a result of their condition or related complications.

Survey respondents also provided insights on the impact new therapies could have on their practice from a list of options, where more than one option could be selected. Most respondents (71%) reported that the primary impact of new therapies for inherited blood disorders on clinical practice will be in providing improved patient outcomes. However, a larger proportion of respondents (86%) highlighted the lack of innovative reimbursement models as a limitation of new therapies. When asked about potential limitations of gene therapies, three-fourths of respondents (75%) expressed concerns about payers’ willingness to cover cell and gene therapies.

Insights on Health Insurance Expenses From New Therapies

Despite the potential of gene therapy to transform the lives of patients with inherited blood disorders, the panelists raised concern about the financing of the high upfront costs for treatments and about the ability of the employer-sponsored insurance system in the United States, particularly in small firms, to pay for these treatments. Health insurance expenses are experiencing a significant increase in 2024.²⁶ In addition, there is upward pressure on health benefit costs from ongoing developments in the health care market, such as the consolidation of health systems and the introduction of cell and gene therapies. Payers also cite price increases for medical care and prescription drugs as a key driver of premium growth in 2024, including the demand for glucagon-like peptide-1 drugs being used to treat diabetes and obesity.

“I have employers that are very committed to their employee health benefit. I mean, they love their employees and they’ve seen 20%-30% increases in [health care] premiums every year. And now they’re getting to the point where they just can’t do it.” – Employee Benefit Expert, Market Insights panelist

The panelists acknowledged that cell and gene therapies represent a rapidly expanding category of treatments with the potential to address challenging diseases like SCD, β-thalassemia, and hemophilia. Although the use of these therapies can entail significant risks and prolonged hospital stays, there is a growing level of interest regarding these treatments. These therapies are typically administered as a one-time course of treatment, often costing more than $2 million per patient.²⁷ This high, upfront expenditure places a different financial strain on payers depending on business models (Figure 1) and line of business, making it challenging for payers to cover the expenses associated with high-investment therapies.

FIGURE 1.

Fixed and Variable Costs in Fully Insured and Self-Funded Plans

For example, state Medicaid programs are obligated to provide coverage for all drugs approved by the FDA if the drug manufacturer has entered into a federal Medicaid rebate agreement.²⁸ However, there is considerable variation in how states approach the coverage of cell and gene therapies. As for Medicare, it covers services deemed reasonable and necessary for the diagnosis or treatment of an illness or injury, with most coverage policies determined by local Medicare administrative contractors, some at the national level (national coverage determinations) and some on a case-by-case basis.²⁹ In commercial coverage, there are no federal mandates requiring plans to include specific drugs, although some states have mandates, and plans in the individual and small group market must cover essential health benefits that establish minimum standards for prescription drug coverage.³⁰ Commercial payers typically use secondary reinsurance policies and stop-loss products to manage the costs associated with high-investment cell and gene therapies. With the flexibility to define the benefit package provided under self-funded health plans, some employers are opting to exclude coverage for cell and gene therapies from their benefit offerings.³¹ Securing reinsurance for high-investment therapies is a vital step for commercial payers. Numerous organizations provide reinsurance programs tailored to these therapies, enabling self-insured plan sponsors to make fixed monthly payments per member in exchange for transferring the claims risk associated with high-investment treatments.

Insights on Stop-Loss Insurance Coverage

The panelists were provided with an overview presentation of stop-loss insurance, a product that provides financial protection against high-cost, catastrophic, and unpredictable losses (health care claims), to examine the implications of trends in stop-loss policies. Stop-loss insurance is purchased by employers who have decided to self-fund their employee benefit plans but do not want to assume 100% of the liability for losses arising from the plans (Figure 2). Under a stop-loss policy, the stop-loss carrier becomes 100% liable for losses that exceed a certain limit called a deductible. Stop-loss contracts are renewed annually, and each year, the claims are analyzed to set stop-loss premium rates for the next year. A higher deductible may be put in place for high-cost claimants with predictable, ongoing health care claims that are expected to be higher than the quoted employer group deductible. This higher deductible is called a laser. Stop-loss insurance is a reimbursement product; it does not directly pay employees or providers. It reimburses employer groups for claims that the groups have already paid to the providers.

FIGURE 2.

Self-Funded Plans Stop-Loss Insurance Coverage

The current system of self-funded employer groups purchasing stop-loss coverage is expected to cover the payment of cost-effective gene therapies. However, there are concerns about the long-term resilience of the payer systems as stop-loss premiums continue to increase or if there is increased use of therapies that are not cost-effective.³² Several panelists voiced concerns that the existing conventional treatments for some inherited blood disorders are considered not cost-effective. Therefore, they argue that a cost-effective model needs to consider that the base alternative treatment price may also not be cost-effective.

“And you know, inherited blood disorders are just one piece of the huge pie for us. You know, we have NICU admissions, complex oncology, and lots of high-cost drug therapies that’s been going on for 10+ years. So, this is just another very big piece of that very large cost-of-care pie. And then who pays for it? That’s the big question.” – Employee Benefit Expert, Market Insights panelist

Insights on Contracting Considerations

As the panelists assessed opportunities with different contracting and reimbursement models, they highlighted that the complexities of contract negotiations for cell and gene therapies may be compounded by the complex care delivery requirements. Creating value-based contracts for gene therapies will likely involve the participation of multiple parties, possibly exceeding 4, which introduces additional layers of intricacy. Ensuring effective coordination and the establishment of clear patient selection/eligibility criteria will be crucial to achieving consensus among all parties involved. Additionally, a panelist commented that when manufacturers face potential financial risks, they may be inclined to limit risk-sharing agreements to include younger, healthier patients, potentially conflicting with the preferences of both clinicians and patients who are eager to benefit from possibly curative treatments.

Panelists recommended using a transplant contracting model as a foundational starting point when considering contracts for the SCD gene therapies, while also incorporating the manufacturer into the equation. The contracting process for hematopoietic stem cell transplant is distinctive in that it typically involves separate contracts for each phase of care, encompassing evaluation, pretransplant procedures, the transplant itself, and posttransplant follow-up care.

“Single case agreements are good right now, because the volume is low. But thinking about the next several years when we have therapies that are going to be impacting more patients, will we be able to treat more patients?” – Patient Representative, Market Insights panelist

Payers emphasized that contracting agreements would differ depending on the specific gene therapy and the care delivery needs associated with the gene therapy, including use of single patient or single case agreements. Payers pointed out that the existing contract for the β-thalassemia gene therapy represents a simple contracting model, featuring a single upfront payment that can be combined with an outcomes-based agreement. As part of that agreement, the manufacturer will reimburse contracted commercial and government payers up to 80% of the cost of the therapy if a patient fails to achieve and maintain transfusion independence up to 2 years following the gene therapy infusion.³³ This outcome measure is recognized by payers and providers as clinically meaningful and a straightforward way to track outcomes through claims data. However, some payers made a point to recommend that measured outcomes need to relate to actual health care savings, not cost avoidance. Another cautionary point highlighted by the panelists pertains to the development of contract solutions centered around rebates, given that not all plans transfer rebates to employers.

“We have to get to the point where we’re ready to talk about the hard things… All the different parties, the payers, the PBMs, the manufacturers, the providers, everybody’s got to sit at the table, and we all have to agree that nobody’s going to get everything they want. But our health care system is not sustainable at this rate. We have to make some accommodations if we want people to still get care.” – Payer, Market Insights panelist

Future Directions

POLICY CHANGES

Medicaid expansion or insurance plans that offer lower deductibles for vulnerable populations are considered as potential solutions to affordability concerns around innovative treatments in inherited blood disorders. A national expansion of Medicare or Medicaid to cover treatments exceeding a specific dollar threshold was also viewed by the panelists as a possible approach to maintain equitable access to cutting-edge treatments.

“I would imagine over time, as Medicare and Medicaid struggle with these costs, that [they] might open the dialogue for what is probably the only real solution, which is to leave primary care and all the preventative stuff to the employers and to the free market. But when you’re dealing with things as complex as this $3 million gene therapy, it’s probably going to have to be a national Medicare expansion of some kind that everyone pays into.” – Employee Benefit Expert, Market Insights panelist

RISK-SHARING AGREEMENTS

Given the intricacies of outcomes-based agreements and the substantial financial stakes involved, both payers and manufacturers will need to consider the feasibility of a centralized database and processes for defining and monitoring clinical outcomes. The use of a third-party administrator could streamline the process without raising antitrust concerns. Payers expressed interest in a centralized database that both facilitates yearly assessment of risk-sharing agreements and tracks long-term patient outcomes.

Several panelists highlighted that although risk-sharing agreements offer potential in reducing economic uncertainties, they are intricate and demand planning, execution, and oversight to ensure they effectively meet the objectives of all involved parties. To gain a deeper understanding of risk-sharing opportunities, payers are actively seeking insights from emerging models like the CMS Alzheimer disease registry and the Cell & Gene Therapy Access model.

The upcoming Cell & Gene Therapy Access model, led by the CMS Innovation Center, will test a novel approach to administer outcomes-based agreements, facilitating Medicaid enrollees’ access to potentially life-changing, high-cost therapies. Specifically, the model aims to establish a partnership among CMS, pharmaceutical manufacturers, and state Medicaid agencies. This initiative will evaluate various conditions, including gene therapies for SCD.^3,34 This model creates a new financing approach and would allow state Medicaid agencies to delegate authority to CMS to coordinate and facilitate outcomes-based payment arrangements with cell and gene therapy manufacturers. The intent of the model is to provide access to the 2 recently approved gene therapy products for SCD for individuals insured by Medicaid. Participation by state Medicaid programs will be optional.³⁵ CMS would take on the responsibility of implementing, monitoring, reconciling, and evaluating the financial and clinical outcomes outlined in the agreements.

“Some payers’ value-based agreements [for gene therapies] do have a document that the patient signs that says that they are going to continue to give access to their medical records for a certain time after. And that’s kind of one thing that I expected to see payers doing because the one variable in all of this that is out of the clinicians’ or payers’ control is the behavior of the patient.” – Patient Representative, Market Insights panelist

Panelists emphasized that data harmonization, particularly when dealing with data from multiple health systems or manufacturers that require aggregation and analysis for decision-making, will play a key role in the development of any centralized database and accompanying processes. This is essential for ensuring that the data can be effectively integrated, standardized, and used cohesively to inform decisions and streamline operations.

QUALITY IMPROVEMENT

A potential avenue for quality improvement was discussed, involving the creation of a virtual specialist network modeled after the tumor board concept commonly used in oncology. The aim would be to strengthen collaboration and coordination among hematologists and the broader care team. This type of network holds the potential to address shortages of qualified specialists by offering telemedicine and telehealth services, thereby enhancing access to care, especially for patients in remote or underserved areas.

When combined with decision support tools, like an emergent bleed treatment pathway designed to standardize the management of urgent bleeding episodes in patients with hemophilia in the emergency department, this kind of virtual network could significantly enhance the quality of care provided during critical situations. Panelists also emphasized that a virtual specialist model, along with a pain treatment pathway, could be readily extended to individuals experiencing a pain crisis due to SCD.

“When a prostate cancer patient comes into the emergency room with hip pain, there’s no side eye, there’s no problem, because we all know they could have bone metastasis. But when a patient with SCD comes into the ER with hip pain, well, they go through an evaluation for everything from drug addiction to you’re not educated enough to know what’s wrong with you… It’s one of the few diseases where you go through these types of hoops.” – Patient Representative, Market Insights panelist

Summary

The panelists from the second AMCP Market Insights Program on inherited blood disorders acknowledged that the new treatments are groundbreaking and require distinctive contracting solutions while stressing the need to reduce administrative complexities. For SCD gene therapies, they suggested using the transplant contracting model as a starting point, involving risk-based contracts between payers, providers, and manufacturers, along with designated care sites. The panel also outlined challenges in monitoring and reporting treatment outcomes and proposed options for structuring contracting and reimbursement models owing to the complexity of the US health care system. They emphasized the importance of establishing disease registries specific to inherited blood disorders and developing a value-based infrastructure, similar to that used in oncology, to promote further advancements.

“I’d love to see an extension of the Enhancing Oncology Model, that’s not just oncology, but for these high-cost therapeutics. So, we can steward the total cost of care.” – Integrated Delivery System, Market Insights panelist

When shaping coverage policies, the experts emphasized the importance of a patient-centered approach, with a specific focus on preserving organ function to ensure patients with inherited blood disorders remain eligible to receive future gene therapies.

Funding Statement

This supplement was conceptualized by AMCP and Michelle Rice and Associates, LLC. The AMCP Market Insights Program described in this supplement was supported through funding by BioMarin, CSL Behring, Sanofi, Spark Therapeutics, and Takeda. BioMarin, CSL Behring, Sanofi, Spark Therapeutics, and Takeda manufacturer multiple medications for the treatment of inherited blood disorders. Publication of the supplement was funded by AMCP.