On Friday morning, February 15, 2019, CMS released its proposed national coverage determination on CAR-T therapies. Therapies (whether inpatient or outpatient), are covered, but there are some (commonsensical) requirements on the hospital and the patient must be in a CAR-T outcomes registry.
There is also a clause for coverage that is not necessarily on-label, but endorsed in a compendium.
Early press from Reuters here. Trade press at Biopharma Dive, here. Modern Healthcare, here. MedCity News here.
The full NCD is online at CMS, here.
Full text of the decision is clipped below the break. For the full NCD, which prints at 56 PDF pages, see online. Comment is open for 30 days (to 3/17/2019).
Kymriah and Yescarta CAR-T's are not the most expensive CMS drugs; Luxturna is, at $900,000 (here).
The NCD appears to cover autologous treatment (patient's own cells, re-engineered), but there are efforts underway to potentially use non-autologous CAR-T cells also (MedCity, here; companies include San Diego's Allogene Therapeutics).
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A. The Centers for Medicare & Medicaid Services (CMS) proposes to cover autologous treatment with T-cells expressing at least one chimeric antigen receptor (CAR) through coverage with evidence development (CED) when prescribed by the treating oncologist, performed in a hospital, and all of the following requirements are met:
- Patient has:
- Relapsed or refractory cancer; and
- not currently been experiencing any comorbidity that would otherwise preclude patient benefit.
- The hospital has:
- 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 agents and allows for appropriate patient isolation as necessary for evaluation and treatment; and
- written guidelines when administering CAR T-cell therapy for patient communication, monitoring, and transfer to an intensive care unit.
- The treatment meets the criteria in section a or b, below:
- Treatment is an FDA-approved biological, providing targeted therapy for a known antigen expressed in the patient’s cancer according to an FDA indication in a hospital. Repeat 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. In addition, all of the following requirements must be met:
- If the patient is administered CAR T-cell therapy in the inpatient hospital setting, then the patient must be enrolled in, and the furnishing hospital is participating in, a prospective, national, audited registry that consecutively enrolls patients, accepts all manufactured products, follows the patient for at least two years, adheres to the standards of scientific integrity and relevance to the Medicare population as identified in section A.4 of this decision, and answers the three following CED questions:
- How do patient outcomes compare to either the pivotal clinical trial(s) (i.e., the clinical trial(s) that served as the basis for FDA approval of the biological and/or for the FDA indication) of the biological or a cohort of controls receiving standard of care treatment?
- How do the clinical characteristics of registry patients compare to the pivotal clinical trial(s)?
- How do the clinical characteristics of registry patients affect the clinical endpoints relative to those in the pivotal clinical trial(s)?
- If the patient is administered CAR T-cell therapy in the outpatient hospital setting, then the patient must be enrolled in, and the furnishing hospital is participating in, a prospective, national, audited registry that consecutively enrolls patients, accepts all manufactured products, follows the patient for at least two years, adheres to the standards of scientific integrity and relevance to the Medicare population as identified in section A.4 of this decision, and answers the four following CED questions:
- How do patient outcomes compare to either the pivotal clinical trial(s) (i.e., the clinical trial(s) that served as the basis for FDA approval of the biological and/or for the FDA indication) of the biological or a cohort of controls receiving standard of care treatment?
- How do the clinical characteristics of registry patients compare to the pivotal clinical trial(s)?
- How do the clinical characteristics of registry patients affect the clinical endpoints relative to those in the pivotal clinical trial(s)?
- How does the patient report their symptom function health-related quality of life changes over the course of their treatment?
- The furnishing hospital shall address the CED questions on all registry patients by tracking the following clinical data elements at baseline, at treatment, and at follow-up 3 months, 6 months, 12 months, and 24 months after the treatment is administered.
- Age, gender and comorbidities;
- specifics of cancer diagnosis (e.g., sub-classification, stage);
- number(s) or line(s) of previous therapies, therapeutic agents previously administered;
- days to disease progression;
- days to recurrence;
- overall survival; and
- progression-free survival.
- To address a CED question on health-related quality of life, the National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS®) or Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAETM) patient-reported outcome assessment must be used at baseline, at treatment, and at follow-up 3 months, 6 months, 12 months, and 24 months after the treatment is administered.
- If the patient is administered CAR T-cell therapy in the inpatient hospital setting, then the patient must be enrolled in, and the furnishing hospital is participating in, a prospective, national, audited registry that consecutively enrolls patients, accepts all manufactured products, follows the patient for at least two years, adheres to the standards of scientific integrity and relevance to the Medicare population as identified in section A.4 of this decision, and answers the three following CED questions:
- Treatment is an FDA-approved biological, indicated for use identified in the National Comprehensive Cancer Network Drugs & Biologics Compendium with grade 2 or 1 on or after August 2017, and providing targeted therapy in a hospital for a known antigen expressed in the patient’s cancer. In addition, all of the following requirements must be met:
- Patients must be enrolled in a CMS-approved clinical study that consecutively enrolls patients and follows the patient for at least two years. The study shall adhere to the standards of scientific integrity and relevance to the Medicare population as identified in section A.4, and collect all data necessary, including health outcomes, and submit to CMS for approval a written executable analysis plan to address all of the following CED questions:
- How do study patient outcomes compare to a cohort of controls receiving standard of care treatment?
- How do the clinical characteristics of study patients compare to a cohort of controls receiving standard of care treatment?
- How do the clinical characteristics of study patients affect the clinical endpoints relative to a cohort of controls receiving standard of care treatment?
- How does the patient report their symptom function and health-related quality of life changes over the course of their treatment?
- The CED study shall address the CED questions on all study patients by tracking all the clinical data elements specified in A.3.a.iii-iv at baseline, at treatment, and at follow-up 3 months, 6 months, 12 months, and 24 months after the first treatment is administered.
- Patients must be enrolled in a CMS-approved clinical study that consecutively enrolls patients and follows the patient for at least two years. The study shall adhere to the standards of scientific integrity and relevance to the Medicare population as identified in section A.4, and collect all data necessary, including health outcomes, and submit to CMS for approval a written executable analysis plan to address all of the following CED questions:
Registries must be reviewed and approved by CMS. Potential registry sponsors must submit all registry documentation to CMS for approval including the written executable analysis plan and auditing plan. CMS will review the qualifications of candidate registries to ensure that the approved registry follows standard data collection practices and collects data necessary to evaluate the patient outcomes specified above. The registry’s National Clinical Trial number must be recorded on the claim. - Treatment is an FDA-approved biological, providing targeted therapy for a known antigen expressed in the patient’s cancer according to an FDA indication in a hospital. Repeat 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. In addition, all of the following requirements must be met:
[Section 4 is boilerplate that is used and re-used for all CMS NCD CED studies:]
4. All CED studies must adhere to the following standards of scientific integrity and relevance to the Medicare population:
- The principal purpose of the study is to test whether the item or service meaningfully improves health outcomes of affected beneficiaries who are represented by the enrolled subjects.
- The rationale for the study is well supported by available scientific and medical evidence.
- The study results are not anticipated to unjustifiably duplicate existing knowledge.
- The study design is methodologically appropriate and the anticipated number of enrolled subjects is sufficient to answer the research question(s) being asked in the National Coverage Determination.
- The study is sponsored by an organization or individual capable of completing it successfully.
- The research study is in compliance with all applicable Federal regulations concerning the protection of human subjects found in the Code of Federal Regulations (CFR) at 45 CFR Part 46. If a study is regulated by the Food and Drug Administration (FDA), it is also in compliance with 21 CFR Parts 50 and 56. In addition, to further enhance the protection of human subjects in studies conducted under CED, the study must provide and obtain meaningful informed consent from patients regarding the risks associated with the study items and/or services, and the use and eventual disposition of the collected data.
- All aspects of the study are conducted according to appropriate standards of scientific integrity.
- The study has a written protocol that clearly demonstrates adherence to the standards listed here as Medicare requirements.
- The study is not designed to exclusively test toxicity or disease pathophysiology in healthy individuals. Such studies may meet this requirement only if the disease or condition being studied is life threatening as defined in 21 CFR §312.81(a) and the patient has no other viable treatment options.
- The clinical research studies and registries are registered on the www.ClinicalTrials.gov website by the principal sponsor/investigator prior to the enrollment of the first study subject. Registries are also registered in the Agency for Healthcare Quality (AHRQ) Registry of Patient Registries (RoPR).
- The research study protocol specifies the method and timing of public release of all prespecified outcomes to be measured including release of outcomes if outcomes are negative or study is terminated early. The results must be made public within 12 months of the study’s primary completion date, which is the date the final subject had final data collection for the primary endpoint, even if the trial does not achieve its primary aim. The results must include number started/completed, summary results for primary and secondary outcome measures, statistical analyses, and adverse events. Final results must be reported in a publicly accessibly manner; either in a peer-reviewed scientific journal (in print or on-line), in an on-line publicly accessible registry dedicated to the dissemination of clinical trial information such as ClinicalTrials.gov, or in journals willing to publish in abbreviated format (e.g., for studies with negative or incomplete results).
- The study protocol must explicitly discuss beneficiary subpopulations affected by the item or service under investigation, particularly traditionally underrepresented groups in clinical studies, how the inclusion and exclusion criteria effect enrollment of these populations, and a plan for the retention and reporting of said populations in the trial. If the inclusion and exclusion criteria are expected to have a negative effect on the recruitment or retention of underrepresented populations, the protocol must discuss why these criteria are necessary.
- The study protocol explicitly discusses how the results are or are not expected to be generalizable to affected beneficiary subpopulations. Separate discussions in the protocol may be necessary for populations eligible for Medicare due to age, disability or Medicaid eligibility.
Consistent with section 1142 of the Act, the Agency for Healthcare Research and Quality (AHRQ) supports clinical research studies that meet the above-listed standards and address the above-listed research questions.
B. Noncoverage
CMS proposes to non-cover the use of T-cells expressing at least one CAR that is not an FDA-approved biological.
We propose treatment using T-cells expressing at least one CAR when cancer patients do not have a cancer that meets any of the indications noted in A.1.a of this proposed decision would be non-covered.
We propose treatment using T-cells expressing at least one CAR when not indicated in A.2.a or A.2.b of this proposed decision would be non-covered.
C. Other
This policy continues coverage for routine costs in clinical trials that use CAR T-cell therapy as an investigational agent that meet the requirements listed in NCD 310.1.
