Introduction
Autologous chimeric antigen receptor (CAR) T-cells—which are “living drugs”—are promising, emerging therapeutics in immuno-oncology. One example of these “living drugs” is Kymriah (tisagenlecleucel). The drug, a CD-19 directed genetically modified autologous T-cell, was approved by the U.S. Food and Drug Administration (FDA) on August 30, 2017. Kymriah is approved for use in patients up to 25 years of age with the cancer B-cell precursor ALL (acute lymphoblastic leukemia)—a cancer of the blood and bone marrow—that is refractory or in second or later relapse.
In one multicenter clinical trial, 63 pediatric and young adult patients with relapsed or refractory B-cell precursor ALL displayed an overall 83 percent remission rate within three months of treatment with Kymriah. Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research (CBER) stated: “Not only does Kymriah provide these patients with a new treatment option where very limited options existed, but a treatment option that has shown promising remission and survival rates in clinical trials.”
Kymriah can cause severe side effects, however, and consequently carries a black box warning for cytokine release syndrome and neurological toxicities. Therefore, Kymriah is only available through a restricted distribution program under a Risk Evaluation and Mitigation Strategy (REMS). At least one review has questioned the safety and long-term impacts of CAR T-cell therapy. Kymriah is a different drug for each patient because it is made by genetically modifying each patient’s own T-cells. Also, in addition to being cutting-edge and highly effective, Kymriah is expensive: the drug entered the U.S. market with a $475,000 price tag for one course of therapy.
Another CAR T-cell therapy, Yescarta (axicabtagene ciloleucel), was approved by the FDA on October 18, 2017, to treat adults with relapsed or refractory large B-cell lymphoma. Like Kymriah, Yescarta is CD-19 directed and carries a black box warning for cytokine release syndrome and neurological toxicities. Yescarta is only available through a restricted distribution program under a REMS and comes with a price of $373,000 for a course of therapy.
With this information, there are several takeaways regarding the current available CAR-T cell therapies, including the following:
- cutting-edge “living drugs;”
- demonstrating impressive clinical trial efficacy;
- administered through restricted distribution under a REMS; and
- expensive for a course of therapy.
The last point—the expense of CAR T-cell therapies—is important to patients and payers, such as private insurers and the U.S. government. Patients, such as those enrolled in Medicare, need to understand if and when CAR T-cell therapies will be covered, as the cost of these “living drugs” would likely be prohibitive for the average U.S. citizen. In addition, pharmaceutical companies who market, or intend to market, FDA-approved CAR T-cell therapies will need to know the patient population that may be covered by payers when making their pricing and marketing decisions. Thus, the following Centers for Medicare and Medicaid Services’ (CMS’) recent announcement, outlined below, is of significant importance.
The CMS Announcement
Recently, the CMS announced that the current presidential administration finalized its decision to cover FDA-approved CAR T-cell therapy. The announcement noted that “President Trump is committed to strengthening the Medicare program by ensuring that beneficiaries have access to new and potentially lifesaving treatments.” The announcement also noted that Medicare “will cover CAR T-cell therapies when they are provided in healthcare facilities enrolled in the FDA risk evaluation and mitigation strategies (REMS) for FDA-approved indications (according to the FDA-approved label).” It is worth pointing out, as described above, that these coverage determinants (e.g., FDA approved, CAR T-cell therapy, restricted distribution, and administration under a REMS) are present for Kymriah and Yescarta.
“In addition, Medicare will cover FDA-approved CAR T-cell therapies for off-label uses that are recommended by CMA [Center for Medicare Advocacy]-approved compendia.” Acting FDA Commissioner Ned Sharpless, M.D., also stated that the FDA “know[s] there are relatively limited data about the use of these life-saving therapies in the Medicare population” and that the administration “will also continue to carefully assess the benefits and risks when considering whether to approve new CAR T-cell products.” The National Cancer Institute (NCI) will also support the expansion of the Cellular Immunotherapy Data Resource to include “more cancer patients in the Medicare program and others being treated with CAR T-cell therapies.” To date, the NCI has collected high-quality data, “including demographics, tumor characteristics, course of cancer treatment, cellular product manufacturing details, and adverse events and outcomes for 1,400 patients treated with cancer CAR T-cell therapies.”
A CMS decision memo provides a detailed review of the procedural pathway, clinical data, organizational recommendations, questions, and agency considerations leading up to the CMS’ coverage decision. In addition to stating which FDA-approved CAR T-cell therapies will be covered, the decision memo notes that the use of non-FDA approved autologous T-cells expressing at least one CAR is not covered and that routine costs in clinical trials that use CAR-T cell therapy as an investigational agent that meet (the requirements listed in NCD 310.1) will continue to be covered.
Conclusion
The CMS’ announcement and decision memo are important for patients; payers; pharmaceutical companies marketing, or planning to market, FDA-approved CAR T-cell therapies; and biosimilar manufacturers. Pharmaceutical companies that anticipate seeking Medicare coverage for CAR T-cell therapies should therefore plan on putting into place restricted distribution and a REMS, in addition to seeking FDA approval, Biosimilar applicants, in planning for market entry, should consider the effect of needing to address restricted distribution and a REMS.
Charles Andres contributed to the preparation of this WSGR Alert.
