In the cell and gene therapy space, science continues to outpace commercialization. Take, for example, the first two sickle cell disease gene therapies approved by the Food and Drug Administration, Vertex’s Casgevy (exagamglogene autotemcel) and bluebird bio’s Lyfgenia (lovotibeglogene autotemcel). Both were granted marketing authorization in December 2023. But by August of this year only 20 patients had initiated Casgevy treatment and there were just four patient starts on Lyfgenia, according to Managed Healthcare Executive.
The Biden Administration announced this week that the manufacturers of Lyfgenia and Casgevy have entered into agreements with the Centers for Medicare and Medicaid Services to participate in the Cell and Gene Therapy Access Model, which allows CMS to negotiate outcomes-based agreements on behalf of state Medicaid programs for cell and gene therapies, beginning with sickle cell disease treatments. If successful, this could serve as a blueprint for other cell and gene therapies that have faced considerable barriers with respect to patient access.
Sickle cell disease is a group of congenital red blood cell disorders, named sickle cell for their crescent shape. The disease alters the structure of hemoglobin, the molecule in red blood cells that delivers oxygen to organs and tissue throughout the body. As a result, this causes severe pain, anemia, organ damage and infections. Individuals with the disease have a shorter life expectancy, by more than 20 years on average. The most common sickle cell disorder type is sickle cell anemia.
The condition affects millions of people worldwide. In the United States, approximately 100,000 individuals are living with the disease, which predominantly impacts people of sub-Saharan African descent.
Besides pain medications to relieve symptoms as well as antibiotics to treat infections, hydroxyurea—a bone marrow suppressive agent that decreases red blood cell production—can be used to reduce the frequency of painful episodes. It has been in use since the 1980s. The FDA has approved several new therapeutics in the past ten years, but none are as promising as Lyfgenia and Casgevy. These two novel therapies can decrease or potentially eliminate pain crises in patients. Nonetheless, gaining access to the Casgevy or Lyfgenia, listed at $2.2 and $3.1 million, respectively, is difficult.
It’s not just sickle cell disease gene therapies that confront a formidable set of barriers. All cell and gene therapy manufacturers face a challenging environment. The regulatory hurdles are enormous to begin with, but manufacturing challenges following approval are considerable, too. Furthermore, patient preparation, side effect and adverse event profiles can be intolerable. This can deter patients from signing up to initiate treatment. And then there’s not a lot of revenue to squeeze out of the often tiny numbers of patients eligible for treatment. So while the price of each therapy is eye-popping—some are over $1.5 million per treatment—there aren’t many patients taking the therapies. This implies that revenue generation isn’t easy. On top of all of this, payers concerned about the high per unit costs often impose coverage restrictions, as the Tufts Center for the Evaluation of Value and Risk in Health describes.
Nonetheless, gene therapies in particular hold the promise of delivering groundbreaking improvements in health outcomes across multiple disease areas. Therefore, overcoming obstacles to optimal patient access is crucial.
In the case of sickle cell disease treatments, outcomes based agreements are a promising avenue for patient access. Given that Medicaid is a dominant payer—50% to 60%—in the sickle cell disease area, establishing arrangements between manufacturers and state Medicaid agencies is critical.
The voluntary model, led by the Center for Medicare and Medicaid Innovation, aims to test outcomes-based agreements for cell and gene therapies. CMS says that the model will increase access for patients which in turn will likely improve their health outcomes, especially in areas of unmet need, such as sickle cell disease. CMS Administrator Chiquita Brooks-LaSure said that “this is a new frontier in providing access for people with sickle cell disease to potentially transformative treatments.”
The outcomes-based agreements for Lyfgenia and Casgevy will link payments to whether each therapy improves health outcomes. Sickle cell disease could serve as a reasonable test case for OBAs, as it is a disease with outcomes that can be monitored and measured relatively efficiently.
CMS intends to move the process forward by engaging all states that participate in the Medicaid Drug Rebate Program to help them decide whether to participate in the model. Deputy Administrator and Director of the CMS Innovation Center Liz Fowler asserted that the “model will afford state Medicaid agencies more budget predictability.” The risk sharing element through pay for performance is essential in light of the potential for significant outlays should a substantial number of patients opt to take the new treatments.
The model launches next month. Pending whether the next Trump administration decides to keep the model intact, states may choose to begin participation anytime between January 2025 and January 2026. After launching in 2025, this model could expand to include other cell and gene therapies.
