March 15, 2019
Tamara Syrek Jensen, JD
Director, Coverage and Analysis Group
Center for Clinical Standards and Quality
Centers for Medicare & Medicaid Services
7500 Security Boulevard
Baltimore, MD 21244
VIA ELECTRONIC SUBMISSION
RE: Proposed Decision Memo for Chimeric Antigen Receptor (CAR) T-cell Therapy for Cancers (CAG—00451N)
Dear Director Syrek Jensen:
Bristol-Myers Squibb Company (BMS) appreciates the opportunity to submit the following comments on the Proposed Decision Memo for Chimeric Antigen Receptor (CAR) T-cell Therapy for Cancers (CAG—00451N) (Proposed Decision Memo).
BMS is a global BioPharma company whose mission is firmly focused on discovering, developing, and delivering innovative, transformational medicines for patients with serious diseases. BMS has been at the forefront of pioneering personalized medicine and patient-specific approaches to life-threatening diseases. We are the leader in oncology care, developing breakthrough immuno-oncology therapies that improve long-term survival and quality of life for people living with cancer.
We are firmly committed to high-quality, cost-effective care for patients, patient access to medically necessary drug therapies, and the patient community. In light of this commitment, BMS is submitting comments on the Proposed Decision Memo to help ensure that Medicare coverage policy does not adversely affect patient access to innovative, life changing CAR T-cell cancer therapies. These comments are summarized as follows:
- The Centers for Medicare & Medicaid Services (CMS) should not inappropriately limit coverage of future CAR T-cell therapies by too narrowly defining site of care, patient, and treatment eligibility criteria.
- CMS should not inappropriately limit off-label coverage of CAR T-cell therapies by reference to a single compendium.
- CMS should carefully consider the burden of any data collection requirements on smaller, community-based providers that may in the future be able to administer CAR T-cell therapies.
In addition, BMS supports the comments on the Proposed Decision Memo submitted by the Biotechnology Innovation Organization (BIO).
I. CMS Should Not Inappropriately Limit Coverage of Future CAR T-cell Therapies by Too Narrowly Defining Site of Care, Patient, and Treatment Eligibility Criteria
Below, BMS addresses three key components of the proposed scope of CAR T-cell therapies coverage under the Proposed Decision Memo:
- The limitation on coverage of these therapies to the hospital setting;
- The limitation on coverage of these therapies with respect to patients with “relapsed or refractory cancer;” and
- The limitation on coverage to a single dose of a CAR T-cell therapy, unless the patient receives “a new primary cancer diagnosis” from the treating oncologist.
While these proposed limitations would accommodate coverage of the two currently approved CAR T-cell therapies, they do not anticipate CAR T-cell therapies that may be approved in the future, which could be appropriately provided at different sites of care, to patients with different clinical profiles, under different dosing parameters. In short, they are not sufficiently capacious to accommodate coverage of future innovations. Thus, they would unduly restrict coverage of such innovations, and thereby would fail to ensure patient access to therapies necessary for health and survival.
In addition, we urge CMS to avoid unintended consequences of previous national coverage decisions (NCDs) for cancer care.
A. Site of care eligibility criteria
The Proposed Decision Memo would cover CAR T-cell therapies only when provided in the hospital setting. This requirement would limit coverage of future CAR T-cell therapies that may be provided safely and appropriately outside of hospitals, such as at some community cancer centers.
As a leader in oncology care, BMS understands the important role that alternative outpatient settings, like local clinics or community cancer centers, can play in helping to ensure patient access to cancer treatments. For example, rural cancer patients already face challenges in receiving appropriate cancer care. Research has found that 20 percent of the U.S. population is located in a rural area whereas only 3 percent of oncologists are located in these areas. A study of cancer patients in Iowa from 2004 to 2010 found that only 63 percent lived in a hospital service area with a local oncologist, 29 percent lived in areas with only a visiting oncologist, and 8 percent resided in an area that had no oncologist at all. Patients in areas with no oncologist had to travel 58 minutes on average to receive cancer therapy. Especially given that cancer patients in many areas already struggle to access appropriate cancer services, an overly restrictive NCD that unduly limits where patients may access covered CAR T-cell therapies could have severe consequences for patient access to necessary treatment. Enabling such access is essential to the future of cancer care.
Given the evolving – and increasingly personalized nature of cancer therapy – CMS should provide greater site of service flexibility for CAR T-cell therapy. We believe that community cancer centers and physician office settings could serve as a critical care setting for patients receiving this therapy in the future, and respectfully suggest the NCD remain open to that possibility.
Instead of maintaining a prescriptive view of delivering CAR T-cell therapy in a traditional hospital setting, CMS should cover CAR T-cell therapy and any other innovative oncology medicines as long as the therapy is provided at a site of care that meets CMS’s safety standards and is provided in a setting consistent with its Food and Drug Administration (FDA)-approved label. Doing so would allow CMS’s coverage policy to accommodate potential evolution of CAR T-cell therapies.
Notably, CMS is proposing a number of safety and care coordination standards that sites of care must meet in order for CAR T-cell therapy to be covered. Among other things, sites of care must have:
- “[A] Cellular Therapy program consisting of an integrated medical team that includes a Clinical Program Director, a Quality Manager, and at least one physician experienced in cellular therapy, and demonstrates that protocols, procedures, quality management, and clinical outcomes are consistent from regular interaction among all team members;”
- “[A] designated care area that protects the patient from transmission of infectious disease agents and allows for appropriate patient isolation as necessary for evaluation and treatment;” and
- “[W]ritten guidelines when administering CAR T-cell therapy for patient communication, monitoring, and transfer to an intensive care unit.”
Such standards should further allay concerns about the provision of CAR T-cell therapy services at non-hospital sites of care. These proposed requirements also appear to be aligned with the FDA’s requirements under the Risk Evaluation and Mitigation Strategies (REMS) for the products currently on the market.
It is critical that the FDA remain the key decision-maker in assessing product safety and efficacy for determining labeling and needed follow-on monitoring and site training through REMS requirements. As such, it is critical that CMS coverage policies appropriately balance the role of the FDA in development of product labels and ensure patients are able to access treatments as approved by the FDA.
B. Patient eligibility criteria
Under the Proposed Decision Memo, CAR T-cell therapies are covered only for patients with “relapsed or refractory cancer.” The proposed restriction to patients with “relapsed or refractory cancer” appears to be tied to the terms on which the FDA approved existing CAR T-cell therapies. Again, this limitation does not anticipate how CAR T-cell therapies are likely to evolve. The FDA may, in future, approve additional CAR T-cell therapies for conditions other than relapsed or refractory cancer. CMS implicitly recognizes this possibility in the Proposed Decision Memo by citing clinical trials of CAR T-cell therapies for patients with cancers that are not described as “relapsed or refractory.” These include, but are not limited to, the following clinical trials:
- “T-cells Expressing HER2-specific [(CAR)] for Patients with Glioblastoma;”
- “Genetically Modified T-cells in Treating Patients with Recurrent or Refractory Malignant Glioma;” and
- “BCMA-Specific CAR T-Cells Combined with Gamma Secretase Inhibitor (LY3039478) to Treat Relapsed or Persistent Multiple Myeloma.”
If CMS were to finalize an NCD that limits coverage to patients with relapsed or refractory cancer, it would impede patient access to future CAR T-cell therapies for other conditions. BMS urges CMS to finalize an NCD that it sufficiently flexible to accommodate such future innovation.
C. Treatment eligibility criteria
The Proposed Decision Memo provides that “[r]epeat treatment when a patient receives more than one therapeutic dose of a specific CAR T-cell product using the same biological in the same patient is covered only when a new primary cancer diagnosis is made by the treating oncologist and the patient conditions are met.” CMS goes on to say that it recognizes “there may be circumstances when a patient receives more than one therapeutic dose of a specific CAR T-cell product. For this [Proposed Decision Memo], these circumstances are considered to be repeat treatments. . . . We propose this because there is not sufficient specificity in the evidence available on the health outcomes experienced by patients receiving more than one therapeutic dose of a specific CAR T-cell product.”
CMS should not finalize an NCD in a way that would inappropriately limit coverage of CAR T-cell therapies in the future. As CMS itself points out, we are still learning about these therapies and how they may best be used to treat patients in practice. It may be true that, with respect to future therapies, more than one dose may be medically necessary and clinically appropriate, even without a new primary cancer diagnosis. CMS should not finalize the NCD in such a way that could deny coverage to patients whose treatment protocols appropriately call for multiple doses of a CAR T-cells therapy. Instead, CMS should permit coverage where dosing is consistent with the FDA-approved labeling. Patients may not have the time to wait for CMS to revisit the NCD process to expand the scope of coverage every time the FDA approves a CAR T-cell therapy with a different treatment protocol. The NCD should be drafted to avoid this perverse result.
II. CMS Should Not Inappropriately Limit Off-Label Coverage of CAR T-cell Therapies by Reference to a Single Compendia
CMS proposes coverage for off-label uses of CAR T-cell therapies only where the treatment is an FDA-approved biological and the use is identified in the National Comprehensive Cancer Network (NCCN) Drugs & Biologics Compendium “with grade 2 or 1 on or after August 2017.” If the NCD is finalized as proposed, the coverage for CAR T-cell therapies will be narrower than that for other Medicare Part B anticancer therapies. Medicare Part B covers “drugs or biologicals used in an anticancer chemotherapeutic regimen for a medically accepted indication,” which includes uses of a drug or biological for an FDA-approved indication, use of an FDA-approved drug or biological in a listed compendium, and use of an FDA-approved drug or biological that is supported by “peer reviewed medical literature appearing in publications which have been identified for purposes of this subclause by the Secretary.” The statutory list of compendia includes the “American Hospital Formulary Service-Drug Information, American Medical Association Drug Evaluations, the United States Pharmacopoeia-Drug Information, and other authoritative compendia as identified by the Secretary . . . .” The current compendia approved by CMS include American Hospital Formulary Service-Drug Information, the NCCN Compendium, Microdemex Drug Dex, Clinical Pharmacology, and Lexi-Drugs, subject to certain conditions about how the use is listed in those compendia.
The Medicare statute clearly contemplates broad coverage of off-label uses of FDA-approved anticancer chemotherapeutic drugs where an off-label use has a threshold level of support in the literature. Inclusion in a listed compendium is a method specified by statute for determining whether a use has met the threshold level of support. The NCCN Compendium, for example, which is the sole compendium referenced in the Proposed Decision Memo, includes only uses that are supported by the NCCN Clinical Practice Guidelines, which are “evidence-based” and “consensus driven” documents that are updated continuously by a panel of members to assist the decision-making processes of practitioners. Other compendia that CMS itself believes support the use of anticancer therapies similarly derive their listings from an evidence-based process. Allowing coverage of uses supported by these compendia with respect to FDA-approved anticancer drugs or biologicals therefore ensures that a drug or biological will not be covered unless supported by an appropriate level of evidence, while also ensuring that coverage of the drug or biological can become available as knowledge about the uses of the drug or biological evolves, thereby ensuring appropriate patient access to life-altering therapies.
CMS should finalize the NCD for CAR T-cell therapies to permit coverage of off-label uses that is supported by any of the full range of compendia. Consistent with CMS’s coverage of other anticancer therapies, CMS should expand the referenced compendia in the NCD to include all that are applicable to non-CAR T-cell anticancer therapies under section 1861(t)(1) of the Social Security Act (SSA), including the American Hospital Formulary Service-Drug Information, Microdemex Drug Dex, Clinical Pharmacology, and Lexi-Drugs. Because CMS has deemed these compendia to be sufficiently authoritative sources of support for coverage of off-label uses of other anticancer therapies, they are sufficient to support new coverage of off-label uses of CAR T-cell therapies, too. BMS therefore urges CMS to add these other compendia to that listed in the Proposed Decision Memo.
III. CMS Should Carefully Consider the Burden of Any Data Collection Requirements on Smaller, Community-Based Providers That May in the Future Be Able to Administer CAR T-Cell Therapies
The Proposed Decision Memo would cover CAR T-cell therapies through on the ground that CMS does not believe such therapies are “reasonable and necessary” but “show promise in improving health outcomes in patients with cancer.” In support of CED, CMS is proposing a number of data collection requirements for providers with respect to patients receiving care in a hospital consistent with an FDA approved indication or consistent with a use supported by a specified compendium. As noted above, CMS should not limit coverage to care provided in a hospital setting, as doing so could limit coverage of future CAR T-cell therapies in other appropriate outpatient settings. In expanding site of care eligibility criteria to encompass such other settings, CMS should be mindful of how its proposed data collection requirements would apply to smaller, community-based providers.
While BMS applauds CMS for proposing data collection requirements that could be implemented with reduced administrative burden on hospitals, BMS encourages CMS to finalize the data reporting requirements with an eye to ensuring that smaller, community-based provider types, such as community cancer centers, will be able to readily satisfy them, too. Such provider types may not have the same resources or support systems as larger hospitals and therefore may be disproportionately burdened by data reporting requirements. This could, in turn, limit the patient access to CAR T-cell therapies in these important and often more convenient settings.
IV. CMS Coverage Determinations Should Avoid Unintended Consequences of Previous NCDs for Cancer Care
In 2018, CMS approved an NCD for Next-Generation Sequencing (NGS) tests for patients with advanced cancer. During the comment period, community stakeholders supported continued coverage of NGS-based tests outside of FDA labeling by Medicare Administrative Contractors (MACs). The final NCD reflected that distinction; however, when the agency issued instructions to its contractors to align their policies with the NCD and clarify that NGS tests were “non-covered” in all cancer patients who did not have advanced cancer, this had the effect of changing Local Coverage Determination (LCD) and MolDx coverage of certain germline NGS testing that had been covered for years and has become the standard of care for determining risk of developing certain hereditary cancers. CMS has pushed back the implementation date and appears to be re-thinking its guidance, but the action has created significant confusion and disruption to access to these important tests that connect patients with the right therapies.
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BMS appreciates CMS’s efforts to ensure appropriate Medicare coverage of CAR T-cell therapies, but urges CMS to ensure that its policy appropriately accommodates the evolution of such therapies. If you have any questions about these comments, please do not hesitate to contact Amy Demske at (202) 783-8665.
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