An Ethical and Financial Obligation for Sickle Cell Disease Gene Therapy in the United States

New and life-saving therapy for patients with sickle cell disease (SCD) will soon be within reach. Vertex Pharmaceuticals (collaborating with CRISPR Therapeutics) and bluebird bio have each submitted biologic license applications to the U.S. Food and Drug Administration (FDA) for SCD gene therapy, and a rapid decision is expected. These therapies will join stem cell transplantation as the only curative options for adults with SCD.

A report from the Institute for Clinical and Economic Review predicts that the price of SCD gene therapy will be $2 million per patient (1). Given that more than 50 000 patients with SCD may be candidates for gene therapy in the United States (2), the total cost could be more than $100 billion. Despite this cost, other reports indicate that SCD gene therapy is 3 to 6 times more cost-effective than the current noncurative medications (1, 3). Medicare and Medicaid do not consider cost-effectiveness when making coverage decisions, but the Biden administration has committed to funding life-saving therapies for patients with SCD despite financial barriers (4).

This commitment contrasts with the history of inequity experienced by patients with SCD. For example, most U.S. patients with SCD are Black and covered by Medicaid (5). Cystic fibrosis is another rare genetic disease, but patients with this disease are almost exclusively White, and only one third are covered by Medicaid. Patients with cystic fibrosis have benefitted from research funding, new knowledge, and drug approvals—advantages that have been less available to patients with SCD (6).

Disparities like these arise in part from structural racism, discrimination, and their downstream effects (7). Specifically, many patients with SCD have insurance coverage through Medicaid but are at risk because many state Medicaid budgets are constrained by the historical compromises required to pass enabling legislation for Medicare. These historical issues continue to affect the present, as they did when some states rejected federal dollars for Medicaid expansion through the Patient Protection and Affordable Care Act (8).

To address these issues, we propose approaches to gene therapy that do not compromise payer responsibilities but require strong political will. We organize these proposals into 3 categories: triage, price, and financing.

Triage

A triage system would help prioritize potential candidates and reduce overall costs. Triaging patients will be necessary for SCD gene therapy, as it has been for allocation of scarce resources due to cost (such as hepatitis C therapy) or availability (such as COVID-19 vaccines). Triage should be based on the ethical principles of maximizing benefits, minimizing harms, equalizing concern, and prioritizing disadvantaged populations. The criteria for applying these principles could include age, disease intensity (for example, the number of admissions for vaso-occlusive episodes in the past year), the number and severity of complications, and the frequency of required consultations with specialists. Triage would be more equitable for economically disadvantaged patients if the criteria included the area deprivation index or another measure of patient vulnerability. The criteria should be transparent and clear and should include input from stakeholders, such as patient advocacy groups, legislators, and the Centers for Medicare & Medicaid Services (CMS).

Price

Federal involvement should include decreasing the price of gene therapy and subsidizing state Medicaid budgets. Federal intervention on pricing will be particularly important. For example, CMS could require Vertex Pharmaceuticals and bluebird bio to bid for an exclusive national contract, especially because both companies applied for licenses almost simultaneously. A precedent for this approach occurred when some states awarded exclusive contracts to a single manufacturer of hepatitis C antivirals in exchange for lower drug prices, and CMS can more effectively reduce the price of SCD gene therapy than any single state.

The Sickle Cell Disease Comprehensive Care Act (H.R. 1672/S. 904) would cover 100% of medically necessary services to treat SCD. This bill allocates funds for access to FDA-approved SCD therapies and addresses other barriers to care. However, the current budget allocation for CMS in this bill is $50 million, which would cover the anticipated cost of gene therapy for only 25 patients with SCD. Additional funds are needed.

Financing

Innovative financing could reduce upfront costs and promote geographic equity. Although CMS contract bidding would be most effective, either federal or state governments could negotiate long-term payment plans that spread cost out over many years. For example, goal-based payment could depend on patients reaching specific targets and might include a payment for successful administration of the therapy, another payment for molecular evidence of gene changes, and additional payments for improvement in clinical outcomes that could be paid annually for a patient’s lifetime up to a maximum limit (9). Some European countries are using a variant of this type of payment for chimeric antigen receptor T-cell (CAR-T) therapy by dividing an overall payment of €300 000 per patient into several smaller payments over 18 months, subject to the attainment of specific targets.

In addition, other debt-financing arrangements with manufacturers link repayment rates to gene therapy effectiveness. The Cell and Gene Therapy Access Model creates outcomes-based agreements between pharmaceutical companies and state Medicaid programs that are executed by individual states or coordinated by CMS for multistate agreements, and a recent report by the U.S. Department of Health and Human Services prioritizes SCD within this model (10). Moreover, the Maternal Opioid Misuse Model could be adapted by CMS to cover all aspects of SCD care, including gene therapy (4).

To minimize geographic differences from state to state, the federal government should support infrastructure that ensures equitable access across states by basing access on national criteria rather than state financial constraints. A national SCD registry would be necessary to support such a program. In addition, more congressional funds are needed to build capacity for gene therapy administration to address geographic disparities related to access and proximity to expertise.

In summary, we propose new approaches for triaging, pricing, and financing that follow ethical principles and can feasibly reduce the immediate and overall costs of gene therapy for patients with SCD. These proposals should also improve patient access and help address the historical neglect of patients with this disease.