Assessing the state of Medicaid coverage for gene and cell therapies

Gene and cell therapies differ from small-molecule therapeutics in many ways, including the potential to treat the underlying cause of disease with a one-time dosing regimen. Those characteristics make gene and cell therapies highly valuable additions to the healthcare arsenal. However, one-time durable therapies currently come with associated upfront costs that can pose challenges to the US healthcare system, which is designed to support chronic treatments and care. The accessibility of such therapies to patients is of paramount importance to the American Society of Gene and Cell Therapy (ASGCT), which represents over 4,800 researchers, scientists, and clinicians in the field with the core mission of advancing the discovery and clinical application of genetic and cellular therapies to alleviate human disease.

Gene and cell therapies have already demonstrated significant therapeutic benefit in extending and improving the lives of patients with rare genetic conditions. For pediatric patients with spinal muscular atrophy (SMA), treatment with the gene therapy Zolgensma (onasemnogene abeparvovec-xioi) may prevent or slow loss of physical function in a disease that, untreated, is the leading genetic cause of infant mortality.¹ The very first in vivo gene therapy to receive FDA approval, Luxturna (voretigene neparvovec-rzyl), treats a rare genetic form of blindness. Luxturna has demonstrated improvements in functional vision, sustained for 5 years with observations ongoing.² In many cases, the pipeline of gene and cell therapies offers the best hope to families struggling with devastating genetic diseases including sickle cell disease, Duchenne muscular dystrophy, and Batten disease.

State Medicaid programs provide healthcare coverage for low-income Americans and a significant share of children and individuals with disability status, including 37.5% of all American children.³ Medicaid will play a prominent role as a gatekeeper for gene therapies in the coming years since many of the genetic disorders they intend to treat are found disproportionately in these populations.⁴

Despite a federal requirement for Medicaid programs to cover essentially all FDA-approved indications of therapies if the manufacturer has signed the National Drug Rebate Agreement, state Medicaid programs vary widely in whether or how they cover FDA-approved gene and cell therapies. Access problems for families are widely reported. However, information about state coverage policies is difficult to unearth. A 2019 review of coverage policies specific to chimeric antigen receptor (CAR)-T cell therapies found that only 24 states had publicly available policies and that approximately 75% of the available policies had more restrictive criteria than the FDA-approved labeled indication (‘labeled indication’).⁵ For example, just over half of the Medicaid policies identified in that review for Kymriah (tisagenlecleucel) or Yescarta (exicabtagene ciloleucel) specified that patients must not have an active infection including HIV, hepatitis B, or hepatitis C, while half also restricted coverage to patients who had not been previously treated with any CAR-T cell therapy. Neither of those restrictions appears in the labeled indication.

ASGCT undertook a survey of 16 states⁶ and the three largest national Medicaid-managed care organizations (MCOs)⁷ to compare the coverage policies of those states and MCOs with the labeled indication and elucidate additional barriers related to care for three products: Luxturna, a gene therapy for children and adults with an inherited retinal dystrophy caused by mutations in the RPE65 gene;⁸ Zolgensma, a gene therapy to treat children under 2 years old with SMA;⁹ and Kymriah, a CAR-T cell therapy to treat adult relapsed/refractory diffuse large B cell lymphoma (DLBCL) as well as pediatric and young adult acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse.¹⁰ The 16 states chosen reflect more than 46 million covered persons and provide diversity in geography, population characteristics, political leadership, and Medicaid program structure.

ASGCT’s survey of states and MCOs shows the following:

• •For Luxturna, six of the nineteen surveyed payers covered to labeled indication, with two of these six requiring additional documentation to verify coverage. Three of the surveyed payers could be considered more permissive than the labeled indication. Four of the surveyed payers had criteria in addition to, meaning more restrictive than, the labeled indication, and six of the surveyed payers had no coverage information available at all.
• •For Zolgensma, none of the surveyed payers covered to the labeled indication, and no surveyed payers covered indications outside of the labeled indication. Fourteen of the surveyed payers had more restrictive criteria than the labeled indication, while five of the surveyed payers had no information available.
• •For Kymriah, two surveyed states covered to the labeled indication, while one state was more permissive than the labeled indication. Eleven of the surveyed payers had more restrictive criteria than the labeled indication, while five of the surveyed payers had no information available.

Of the states that had policies more restrictive than the labeled indication, most limited access to populations defined by the eligibility criteria for the clinical trial(s) to support approval rather than the population indicated by FDA’s approval and described in the labeled indication.

As Dr. Peter Marks, Director of FDA’s Center for Biologics and Research, noted at the ASGCT 23^rd Annual Meeting, gene therapy phase I/II trials may comprise 5 to 20 participants for initial dose finding and initial efficacy, and a phase II study serving as a pivotal trial may comprise 20 to 100 participants, using historical controls, patient run-in periods, or other novel trial designs.¹¹ The use of limited clinical trial populations for gene and cell therapies is often necessitated by the rare, heterogeneous nature of the specific disease, which drives clinical trial sponsors’ use of narrow trial criteria to enroll participants who behave similarly, such that a treatment effect can be assessed and not be masked by inherent variability in the population.

The statutory standard for determining the effectiveness of a drug in Section 505(d) of the Federal Food Drug and Cosmetic Act does not state nor suggest that the clinical investigations must exactly replicate the populations the product is intended to treat but rather must support such efficacy in the labeled indication as concluded by the scientific experts at the Agency.¹² Our survey, among others, suggests that payers are using narrow clinical trial criteria as policy justifications to limit coverage of potentially lifesaving products, contrary to both the expert scientific opinions of the regulators (FDA) charged with making exactly that determination and to Medicaid drug coverage requirements outlined in existing law and regulations.¹³

While results of ASGCT’s survey are not necessarily representative of all states, the Society’s findings support the conclusion that many Medicaid beneficiaries, including children, face barriers to accessing FDA-approved gene and cell therapies today and in the future. Inconsistent coverage across states and within a state further compounds existing health disparities in the Medicaid population. These barriers and resulting inequities in access are especially concerning for patients with potentially fatal and/or progressive diseases for which early administration of a therapy may significantly prevent or delay associated morbidity and mortality. The Society appreciates that states’ budgeting processes are complex and occur over a short time period and that, relative to traditional therapeutics that mitigate symptoms and are delivered and paid for over time, the higher upfront costs of high-value, disease-modifying, potentially single-administration gene and cell therapies can be a short-term challenge despite their potential for long-term benefits.

ASGCT fully supports modernizing coverage and payment policies to foster patient access to the FDA-approved indication of gene and cell therapies and sufficient reimbursement to providers, including through innovative payment models that account for the unique characteristics of the therapy and the disease it is intending to treat.¹⁴ As the pipeline for cell and gene therapies continues to grow, federal and state regulators must also take proactive steps to ensure that payment systems are ready and designed for this type of innovation. Patients, their caregivers, and the broader healthcare system and society will otherwise continue to lose out.