CGT NOFO_Revised_02.18.25.pdf

U.S. Department of Health and Human Services

Centers for Medicare & Medicaid Services

Center for Medicare and Medicaid Innovation

Cell and Gene Therapy (CGT) Access Model

Notice of Funding Opportunity Type: New

Funding Opportunity Award Type: Cooperative Agreement

Notice of Funding Opportunity Number: CMS-2P2-24-001

Federal Assistance Listings Number (CFDA): AL 93.885

Notice of Funding Opportunity Posting Date: August 15, 2024 (revised as of February 18, 20251)

Applicable Dates:

Letter of Intent to Apply Due Date: N/A

Electronic Application Due Date: March 14, 2025, 11:59 pm EST

Anticipated Issuance Notice(s) of Award: July 1, 2025

Periods of Performance: There are two periods of performance to be aware of in this Model as detailed below:

• Model Performance Period (anticipated): January 1, 2025-December 31, 2035

• Cooperative Agreement Period of Performance (anticipated): July 1, 2025-December 31, 2035

1 This update extends the application deadline from February 28, 2025 to March 14, 2025. All other revisions are non-substantive and do not impact any NOFO funding amounts, activities, requirements, policies, or processes.

Contents

Executive Summary

A. Program Description

A1. Purpose

A2. Authority

A3. General Approach

A4. Model Performance Period and Cooperative Agreement Period of Performance

A5. Background

A5.1 Sickle Cell Disease (SCD)

A5.2 Illustrative Care Journey for SCD Gene Therapy and Potential Access Barriers

A6. Program Requirements

A6.1 Model Participation

A6.2 Model Population

A6.3 Legal Agreements/Cooperative Agreement Award

A6.4 Key Terms

A6.5 State Requirements

A6.6 Optional State Activities

A6.7 Optional Benefit for Sickle Cell Disease

A6.8 Cooperative Agreement Funding Structure

A7. Technical Assistance and Information for Prospective Applicants

B. Federal Award Information

B1. Total Funding

B2. Award Amount

B3. Anticipated Award Dates

B4. Cooperative Agreement Funding Schedule

B5. Number of Awards

B6. Type of Award

B7. Type of Competition

C. Eligibility Information

C1. Eligible Applicants

C2. Cost Sharing or Matching

C3. Letter of Intent

C4. Ineligibility Criteria

C5. Single Application Requirement

C6. Continued Eligibility

C7. EIN, UEI, Login.gov and SAM Regulations

C8. Faith-Based Organization

C9. Other Eligibility Requirements

D. Application and Submission Information

D1. Address to Request Application Package

D2. Content and Form of Application Submission

D2.1 Application Format

D2.2 Standard Forms

D2.3 Application cover letter or cover page (optional)

D2.4 Project Narrative (required)

D2.5 Budget Narrative (required)

D2.6 Program Duplication Assessment (required, maximum 5 pages)

D2.7 Business assessment of applicant organization (required, maximum 12 pages)

D3. Unique Entity Identifier and System for Award Management (SAM)

D4. Submission Dates and Times

D5. Intergovernmental Review

D6. Cost Restrictions

D7. Mandatory Disclosure

D8. HHS Form 690

E. Application Review Information

E1. Criteria

E2. Merit Review and Selection Process

E3. Federal Awardee Performance Integrity Information System (FAPIIS)

F. Federal Award Administration Information

F1. Federal Award Notices

F2. Administrative and National Policy Requirements

F3. Terms and Conditions

F4. Cooperative Agreement Terms and Conditions of Award

F5. Reporting

F5.1 Reporting Requirements and Milestones Linked to NOFO Funding

G. CMS Contacts

G1. Programmatic Questions

G2. Administrative/Budget Questions

G3. Other Information

Appendix I. Guidance for Preparing a Budget Request and Narrative

Appendix II. Application and Submission Information

Appendix III. Business Assessment of Applicant Organization

Appendix IV. Accessibility Requirements

Appendix V. Merit Review and Selection Process

Appendix VI. Application Check-off List

Executive Summary

This Notice of Funding Opportunity (NOFO) announces the opportunity to apply for Cooperative

Agreement funding to support States’ participation in the Cell and Gene Therapy (CGT) Access Model

(the CGT Access Model or “the Model”). Eligible applicants are States, the District of Columbia, and any

U.S. territory that participates in the Medicaid Drug Rebate Program (MDRP). A maximum of $9.55 million may be awarded to each Recipient, depending on the number of States that apply for funding, pending availability of funds.

The CGT Access Model is a voluntary model that tests whether a CMS-led approach to developing and administering outcomes-based agreements (OBAs) for cell and gene therapies (CGTs) improves Medicaid beneficiary access to innovative treatment, improves health outcomes for Medicaid beneficiaries, and reduces health care expenditures. Within this Model, CMS will negotiate standard Key Terms of an OBA directly with manufacturers of gene therapies approved or licensed by the U.S. Food & Drug

Administration (FDA) for the treatment of sickle cell disease (SCD). The negotiated Key Terms will be disclosed to all States in December 2024. After the Key Terms have been disclosed, States: (1) may apply to participate in the Model in response to the State Request for Applications (RFA); and (2) may apply for

Cooperative Agreement funding in response to this NOFO.

Cooperative Agreement funding is intended to support State Model implementation activities and to support States that take steps to improve access to gene therapy and multi-disciplinary, comprehensive care in conjunction with the model test.

To be considered for Cooperative Agreement funding, a State must apply to both the State RFA and this

NOFO. Up to $9.55 million in Cooperative Agreement award funding is anticipated to be available to each selected award recipient over the course of up to 10.5 years. The Cooperative Agreement and the

Model are anticipated to conclude no later than December 31, 2035.

Table 1: Summary

Item Description

HHS Awarding Agency Centers for Medicare & Medicaid Services (CMS)

CMS Awarding Center Center for Medicare & Medicaid Innovation

(Innovation Center)

Notice of Funding Opportunity Title Cell and Gene Therapy (CGT) Access Model

Authorization

Section 1115A of the Social Security Act (the Act) as added by Section 3021 of the Patient Protection and Affordable Care Act (P.L. 111-148)

Federal Assistance Listings Number AL 93.885

Funding Opportunity Type New

Funding Opportunity Number CMS-2P2-24-001

Type of Award Cooperative Agreement

Type of Competition Competitive

Letter of Intent N/A

Application Due Date and Time March 14, 2025 by 11:59 pm EST (Baltimore, MD)

Anticipated Issuance Notice(s) of Award July 1, 2025

Period of Performance Start Date July 1, 2025

Period of Performance End Date December 31, 2035 (anticipated)

Anticipated Total Available Funding $95,500,000 (subject to availability of funds)

Estimated Maximum Award Amount Per

Awardee $9,550,000

Estimated Maximum Number of Awardees

52 (All 50 States, the District of Columbia, and any

U.S. territory that participates in the Medicaid Drug

Rebate Program (MDRP))

A. Program Description

A1. Purpose

This NOFO provides details and instructions on how to apply for funding under the Cell and Gene

Therapy (CGT) Access Model (the CGT Access Model or “the Model”).

The Centers for Medicare & Medicaid Services (CMS) is seeking applications from States, the District of

Columbia, and any U.S. territory that participates in the Medicaid Drug Rebate Program (MDRP)2

(hereinafter, “States”) for optional funding under the CGT Access Model. See Section A6.1.1 State

Participation for more information.

The Model will test whether a CMS-led approach to developing and administering outcomes-based agreements (OBAs) for cell and gene therapies (CGTs):

• improves Medicaid beneficiary access to innovative treatment;

• improves health outcomes for Medicaid beneficiaries; and

• reduces health care expenditures.

Depending on state and manufacturer interest, the Model may also include beneficiaries in separate

Children’s Health Insurance Programs (CHIP).3

Through a Cooperative Agreement award, Implementation Funding will be available to States to support required and optional Model implementation activities (see Section A6.8.1 Implementation Funding).

Additionally, Milestone Funding will be available to States that successfully complete research projects related to increasing access to sickle cell disease (SCD) gene therapy and promoting multi-disciplinary, comprehensive care for beneficiaries with SCD who are considering or receiving SCD gene therapy (see

Section A6.8.2 Milestone Funding).

A2. Authority

Section 1115A of the Social Security Act (the Act) authorizes the Secretary of the Department of Health and Human Services to test innovative payment and service delivery models expected to reduce

Medicare, Medicaid, or CHIP expenditures, while preserving or enhancing quality of care.

A3. General Approach

The Innovation Center is testing the impact of a voluntary model wherein CMS facilitates the development and implementation of OBAs between States and Manufacturers.4 Within this model, CMS will negotiate standard Key Terms5 directly with the Manufacturer. These OBAs may include outcomes-based rebates, volume-based rebates, and guaranteed rebate components.

2 Under section 1927 of the Social Security Act. As of the date of publication of this NOFO, Puerto Rico is the only U.S. territory that participates in the MDRP.

3 Participation with respect to the separate CHIP population would be under a value-based purchasing arrangement.

4 “Manufacturer” means an entity that holds the New Drug Application(s) (NDA(s)) / Biologics License Application(s) (BLA(s)) of a gene therapy with an FDA approved indication for the treatment of sickle cell disease.

5 “Key Terms” means the central parameters of the agreement negotiated with CMS, including rebate calculation and amounts, the duration of the agreement, data sharing arrangements, and any options or variations, that will form the basis for individual

Supplemental Rebate Agreements between the Manufacturer and participating States.

Upon agreement regarding the standard Key Terms between CMS and the Manufacturer, the

Manufacturer will enter into a Participation Agreement (PA) with CMS, and formally become a participant in the Model. The agreed-upon standardized Key Terms will then be communicated to all

States, who may, at their option, execute a State Agreement (SA) with CMS, thus also becoming participants in the Model. Participating States will adopt the Key Terms through a supplemental rebate agreement (SRA) with a participating Manufacturer.6 (See Section A6.3 Legal Agreements for a description of the legal relationships between CMS, Manufacturers, and States.) CMS will support implementation of the Model through such responsibilities as implementing, monitoring, reconciling, and evaluating the financial and clinical outcomes specified in the Key Terms. Under the Cooperative

Agreement, Implementation Funding is available to help States implement the Model (see Section A6.8.1

Implementation Funding); Milestone Funding is available to States who achieve Model milestones (see

Section A6.8.2 Milestone Funding).

At this time, the Model, along with this NOFO, is limited to gene therapies approved or licensed by the

U.S. Food & Drug Administration (FDA) for the treatment of SCD that are covered outpatient drugs under the Medicaid Drug Rebate Program (MDRP) (hereinafter, “Model Drugs”).

A4. Model Performance Period and Cooperative Agreement Period of Performance

There are two periods of performance to be aware of in this Model:

▪ The Model Performance Period; and

▪ The Cooperative Agreement Period of Performance

Model Performance Period: January 1, 2025 - December 31, 2035

The Model is expected to consist of eleven Model Performance Years (PYs).

▪ The first Model Performance Year (PY1) will run from January 1, 2025-December 31, 2025.

▪ Each State has the flexibility of joining the Model anytime during Model PY1, or at the start of

Model PY2 (January 1, 2026). In other words, States may choose whether to begin performance during Model PY1 but must begin performance by the start of Model PY2 (January 1, 2026).

▪ States will specify a Model Performance Period Start Date in response to the State RFA.

For all participating States, the Model Performance Period is anticipated to conclude on December 31, 2035, unless the State’s participation in the Model is terminated earlier.

Depending on the CMS-Manufacturer negotiated Key Terms, the OBA Term may be as long as PYs 1-6.7

Some state obligations will only apply for the duration of the OBA Term, and other state obligations extend for the duration of the Model.

An example that illustrates how periods for gene therapy administration, measurement, and reconciliation specified in the Key Terms may overlap throughout the Model Performance Period is included below and in Figure 1.

6 The State-specific contracts will comport with applicable laws and regulations.

7 "OBA Term" means the time period for which the Key Terms are applicable. In other words, the OBA term is the period of time during which State financial arrangements with the Manufacturer governed by the OBA apply for beneficiaries who receive the Model Drug. The OBA Term is expected to be no more than 6 years, and no related obligations are expected to extend beyond 2035.

• Example: Administration of gene therapy would occur during Model PYs 1-6, and patients who receive gene therapy in each Model PY would represent a different cohort. For each cohort, measurement of outcomes would begin the year following administration of gene therapy and final reconciliation of rebates would follow the measurement period.

Figure 1: Example Model Performance Period

Cooperative Agreement Period of Performance: July 1, 2025 - December 31, 2035

The Cooperative Agreement period of performance is expected to begin as early as July 1, 2025 and end on December 31, 2035.

▪ The Cooperative Agreement Period of Performance is further divided into ten Budget Periods

(BPs).

▪ The first Budget Period is 18 months (July 2025 through December 2026) followed by nine 12-month Budget Periods, as shown in Table 2, below.

The relationship between Model PYs, Cooperative Agreement BPs, and Calendar Years are displayed in

Table 2. BPs correspond to the release of award funding.

Table 2. Relationship between Calendar Years, Model Performance Years (PYs) and Cooperative

Agreement Budget Periods (BPs)

2025 2026 2027 2028 2029 2030 2031 2032 2033 2034 2035

Model

Performance

Years (PYs)

PY1

(States may start at any time)

PY2 PY3 PY4 PY5 PY6 PY7 PY8 PY9 PY10 PY11

Cooperative

Agreement

Budget

Periods (BPs)

No

Funding

(Jan - Jun)

BP1

(July 2025 -

Dec 2026)

BP2 BP3 BP4 BP5 BP6 BP7 BP8 BP9 BP10

A5. Background

Gene therapies are a rapidly growing class of transformative, potentially one-time medicines designed to treat previously intractable diseases.8 Through these novel technologies, it may be possible to correct the underlying causes of a disease, restore functionality, or halt the progression of devastating illnesses, such as SCD. However, the combination of: a) the relative novelty of these products; b) the rare indications on which most gene therapies focus; and c) limited utilization and outcomes data to date, means the long-term curative potential of these therapies remains uncertain. In addition, the typically high cost of these therapies may present affordability and financial predictability challenges for State Medicaid programs and other payers, despite potential downstream savings that may result from avoided progression of these diseases and ongoing treatment costs. In response to these pressures, some payers, including state

Medicaid agencies, are using cost containment and utilization management strategies, as legally permissible, that can have the effect of limiting access to gene therapies.9

One way to capture the positive potential of novel therapies, while addressing the uncertainty regarding their clinical outcomes, is by using an OBA, wherein a payer’s spending for a gene therapy varies based on whether a pre-specified clinical outcome(s) is achieved over a defined period of time. There are a number of possible structures for an OBA, but in its simplest form, a payer and a manufacturer enter into a contract that defines Outcome Measures10 (clinical values, patient-reported outcome (PRO) measures, or utilization of care measures) and a Measurement Period.11 Over the course of the Measurement Period, an entity (such as the payer) tracks the agreed-upon Outcome Measures applicable to an individual beneficiary or population. If pre-defined thresholds for the Outcome Measures are not met, then rebates may be due to the payer, from the manufacturer, at agreed-upon intervals. A retrospective analysis or reconciliation of rebates (i.e., final settlement of the rebate amounts owed and paid) occurs following the conclusion of the Measurement Period.

State Medicaid agencies today can, and do, independently negotiate rebates through SRAs permitted under CMS-authorized State Plan Amendments (SPAs). Specifically, states may enter into SRAs as long as the agreements result in rebates equal to or greater than the federal statutory rebate states receive from the MDRP.12 A number of states have received authorization from CMS to enter specifically into Value-

Based Purchasing SRAs (VBP SRAs), which allow them to operate or enter into OBAs. However, States have reported that their ability to pursue OBAs for gene therapies is curtailed by the complexity in negotiating endpoints and thresholds with manufacturers, the states’ lack of leverage stemming from the lack of alternative treatments and statutory coverage obligations, as well as the burden of data collection and continuous level of effort for evaluation over multiple years.

Through the Model, the Innovation Center will test whether a partnership among CMS, Manufacturers and States related to gene therapies could offer better access to treatment for beneficiaries with rare and severe diseases, and how that access may translate into improved quality and health outcomes. (See

8 Cell and gene therapy represent overlapping fields of biomedical research with similar therapeutic goals, which target DNA or

RNA inside or outside the body. Gene therapy involves making changes to a patient’s genetic material, or DNA, whereas cell therapy involves the infusion or transplantation of whole cells into a patient.

9 “Chapter 1: Addressing High-Cost Specialty Drugs.” June 2021 Report to Congress on Medicaid and CHIP. Medicaid and

CHIP Payment and Access Commission, 2021, available here.

10 “Outcome Measures” mean the agreed-upon clinical or utilization-based factors that are linked to rebates.

11 “Measurement Period” means the time period following administration of the drug during which Outcome Measures will be monitored.

12 42 CFR § 447.502 (defining “CMS-authorized supplemental rebate agreement”).

https://www.macpac.gov/wp-content/uploads/2021/06/Chapter-1-Addressing-High-Cost-Specialty-Drugs.pdf

Section A6.3 Legal Agreements/Cooperative Agreement Award for more information about the legal relationships that will govern this partnership.)

For State participants, the Model aims to reduce the burden of negotiating and implementing OBAs for gene therapies and potentially facilitate the adoption of OBAs in more states. This Model could also facilitate savings to, and improve stability for, States due to financial predictability, greater rebates, and long-term reductions in health expenditures. Through a standardized policy across participating States, this Model also may ease burdens on beneficiaries and providers by improving efficiency in navigating utilization management in the patient’s care journey.

In addition, the Model is expected to expand access to critical supportive services that may remove barriers for beneficiaries for whom the Model Drug is clinically appropriate and would improve health outcomes. This includes, but is not limited to, care coordination, access to SCD specialists, access to behavioral health providers and fertility preservation services. Finally, CMS will take a central role in data collection and monitoring to facilitate the adoption and implementation of OBAs and related monitoring, helping to relieve participants, both Manufacturers and States, of some of that burden. Overall, the Model aims to reduce the burden to States and Manufacturers of operating an OBA, while maximizing access to novel and transformative therapies for beneficiaries.

A5.1 Sickle Cell Disease (SCD)

SCD is an inherited, genetic blood disorder that causes blood cells to become rigid and irregularly, abnormally shaped due to an abnormality in hemoglobin – the protein that carries oxygen throughout the body – resulting in blood flow obstruction, painful vaso-occlusive crises (VOCs), anemia, and serious complications including acute chest syndrome, stroke, and bacterial infections. This condition is the most prevalent genetic blood disorder in the nation, affecting more than 100,000 people in the United States.13

Medicaid is a disproportionate payer for individuals with SCD. SCD is a costly condition, particularly for the Medicaid program, as approximately 50-60% of people with SCD are enrolled in Medicaid.14 The total cost to the health system of SCD is estimated at $2.98 billion per year in the United States.15 This estimation does not take into account the social costs of the disease, including lost time at school or work for both patients and, in many cases, caregivers.

In December 2023, the FDA approved two gene therapies for the treatment of SCD. Exagamglogene autotemcel (“Casgevy” or “exa-cel,” Vertex Pharmaceuticals and CRISPR Therapeutics) is approved for the treatment of patients 12 years of age and older with SCD and recurrent VOCs.16 Casgevy is manufactured by altering a person’s stem cells to induce the production of fetal hemoglobin, which is a form of oxygen-carrying hemoglobin that is naturally present during fetal development but generally ceases after birth.17 Lovotibeglogene autotemcel (“Lyfgenia” or “lovo-cel,” bluebird bio) is approved for the treatment of patients 12 years of age and older with SCD and a history of vaso-occlusive events

13 “About Sickle Cell Disease.” National Human Genome Research Institute, 2020, available here.

14 Andelson, E., at al. “Medicaid Access & Landscape Review for Prescription Drugs Treating Sickle Cell Disease: Opportunities to Improve Access for Sickle Cell Disease Therapies.” Sick Cells & Avalere Health, 2022, available here.

15 Huo, J., et al. “The Economic Burden of Sickle Cell Disease in the United States.” Value in Health, 2018, available here.

16 “Package Insert - CASGEVY (exagamglogene autotemcel), suspension for intravenous infusion.” Vertex Pharmaceuticals

Incorporated, 2024, available here.

17 “Vertex and CRISPR Therapeutics Present New Data on More Patients With Longer Follow-Up Treated With exagamglogene autotemcel (exa-cel) at the 2022 European Hematology Association (EHA) Congress.” CRISPR Therapeutics, 2022, available here.

https://www.genome.gov/Genetic-Disorders/Sickle-Cell-Disease https://sickcells.org/wp-content/uploads/2022/08/Sick-Cells_Medicaid-Access-and-Landscape-Review_Final-Report.pdf https://www.valueinhealthjournal.com/article/S1098-3015(18)33183-8/fulltext https://www.fda.gov/media/175481/download?attachment https://crisprtx.gcs-web.com/news-releases/news-release-details/vertex-and-crispr-therapeutics-present-new-data-more-patients

(VOEs).18 Lyfgenia is manufactured by adding a functional copy of a modified globin gene into a patient’s stem cells.19

A5.2 Illustrative Care Journey for SCD Gene Therapy and Potential Access Barriers20

Table 3 below outlines elements of the illustrative care journey for gene therapy for individuals with

SCD, which CMS developed in coordination with clinical experts. Table 3 also describes the set of services and supports a beneficiary may need along that journey, and the potential for gaps in those services and supports. Potential care delivery gaps cited below include services that are not covered by

Medicaid (e.g., childcare), optional Medicaid services (e.g., case management, dental care), and mandatory services for which beneficiaries may experience access barriers or delays in services (e.g., access to out-of-state providers). Funding available under this NOFO is designed to help States address some of these potential care delivery gaps. Access barriers may vary from state to state and individual to individual.

18 “Package Insert - LYFGENIA® (lovotibeglogene autotemcel) suspension for intravenous infusion.” bluebird bio, Inc., 2023, available here.

19 Kanter, J., et al. “Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease.” New England Journal of

Medicine, 2022, available here.

20 Table 3 is intended to provide a high-level overview of the care journey for individuals with SCD undergoing gene therapy, which CMS developed in coordination with clinical experts. This table may aid Applicants in identifying service and support gaps in the beneficiary care journey for gene therapy, and producing a comprehensive response to this NOFO that addresses potential gaps in recommended services and supports in the Applicant State. This table is not intended to provide a guide for gene therapy medical providers and is not a CMS recommendation for care or treatment.

https://www.fda.gov/media/174610/download?attachment https://doi.org/10.1056/NEJMoa2117175

Table 3 may aid Applicants in identifying service and support gaps in the beneficiary care journey for gene therapy, and producing a comprehensive response to this NOFO that addresses potential gaps in recommended services and supports in the Applicant State. This table is not intended to provide a guide for gene therapy medical providers and is not a CMS recommendation for care or treatment. The CGT

Access Model does not limit patient rights to make care decisions in consultation with their clinical providers.

Table 3. Illustrative Care Journey for Gene Therapy for SCD and Potential Care Delivery Gaps

Step in Care

Journey

(Length of Time /

Care Setting)

Description of Step in Care Journey Potential Care Delivery

Gap(s)

1. Patient

Identification for

Gene Therapy

(Duration will likely vary by patient access to providers and provider type /

Outpatient)

Patient is identified as a possible candidate for gene therapy by a health care provider based on clinical needs and product eligibility criteria, or patient approaches their healthcare provider with interest in gene therapy. Health care provider refers patient to a health care provider who specializes in

SCD.

• Access to a provider who is knowledgeable about

SCD gene therapy

• Patient awareness of gene therapy

2. Disease

Management by

Hematologist21 who Specializes in SCD

(Duration of patient management and counseling varies according to the needs of the patient /

Outpatient)

Patient is managed by a hematologist who specializes in SCD.22 The hematologist will assess whether the patient’s SCD is being optimally managed (particularly for patients who have not been seen by a hematologist who specializes in

SCD), and if not, will begin appropriate disease management, and assess whether gene therapy is the most suitable treatment course for the patient.

Patients’ mental health and pain should be addressed at this time.

• Access to hematologist who specializes in SCD

• Access to mental health providers and health care providers specializing in pain management and addiction

21 It is ideal for patients to be seen by a hematologist who specializes in SCD; however, patients may also be managed by other health care providers who are knowledgeable about SCD.

22 See, e.g., literature surrounding gaps in access to evidence-based care, including Cronin R., et al., “The Use of FDA-Approved

Medications for Preventing Vaso-Occlusive Events in Sickle Cell Disease,” Blood Advances (2023), available here. See also

“2021 Report to Congress: Sickle Cell Disease Treatment Demonstration Regional Collaboratives Program,” National Institute for Children’s Health Quality (2021), available here, pages 6-18, describing challenges in access to specialty care that aligns with NHLBI promulgated guidelines.

https://ashpublications.org/bloodadvances/article/7/13/3114/494814/The-use-of-FDA-approved-medications-for-preventing https://www.nichq.org/2017-2021-scdtdrcp-report-congress

3. Evaluation for

Gene Therapy and Patient

Education

(~30 days /

Outpatient)

Patient travels to sickle cell23 or transplant center and is evaluated for suitability/“fitness” for gene therapy and educated about the care journey.

This includes both a diagnostic evaluation (e.g., pulmonary function tests, echocardiogram, brain

MRI/MRA, labs, liver MRI, renal assessment, dental evaluation, genetic testing, and social work assessment) and an evaluation of a patient’s ability to adhere to the gene therapy regimen (e.g., compliance with current pain regimen, adequate family/social supports,24 reliable transportation, and reliable communication methods, among others).

Consultation with transplant physicians, hematologists specializing in SCD, psychologists, psychiatrists, and social workers before, during, and after gene therapy is important to educate the patient about gene therapy, manage pain, reduce opioid dependence, help patients manage depression, and set reasonable expectations of what life will be like during and after therapy.25 Patients also need access to reproductive health specialist counseling about the likely impact of gene therapy on their ability to have children in the future, and options for fertility preservation.

Peer counseling by individuals with SCD who have participated in a gene therapy clinical trial or undergone a similar procedure (e.g., bone marrow

• Access to out-of-state providers, if there is no qualified SCD gene therapy provider (or no capacity) in the state

• Access to hematologists and transplant physicians who specialize in SCD

• Access to reproductive health specialists

• Access to dental care

• Beneficiary knowledge of and timely access to non-emergency medical transportation (NEMT)26

• Access barriers,27 including childcare28

• Access to peer counseling and support

• Access to mental health providers and health care providers specializing in pain management and addiction

• Access to care coordination/patient navigation/community

23 There are two principal categorizations of “sickle cell centers.” Under the HRSA Sickle Cell Disease Treatment Demonstration

Program, there are 5 awardee regional “hubs,” which have relationships with 51 participating clinical sites. Each of the hubs and participating sites could be considered a sickle cell “center” based on their provision of multidisciplinary sickle cell specialty care, including behavioral health care focused on opioid addiction, pain management, and depression. There is also a

National Association of Sickle Cell Centers, started by some of the principal investigators in the HRSA program, which includes over 80 certified Sickle Cell Centers.

24 Patients may be required to have a caregiver in order to be considered fit for gene therapy.

25 Individuals with SCD may have behavioral health challenges relevant to their SCD and potential gene therapy, including depression, and opioid dependence, and may have developed an identity as a person living with a debilitating chronic disease.

They may also need education to develop realistic expectations of what their life will be like post-therapy.

26 Many patients will likely need to travel and stay overnight near the center, and some will need to cross state lines to access sickle cell or transplant centers. Many beneficiaries will require assistance with transportation to and from the center, and meals and lodging for themselves and a caregiver while being treated on an outpatient basis at the center.

27 Throughout this document, access barriers refer to things like transportation, housing, nutrition, and childcare. CMS encourages States to review CMS’ framework of services and supports to address access barriers that CMS considers allowable under specific Medicaid and CHIP authorities. “CMCS Informational Bulletin: Coverage of Services and Supports to Address Health-Related Social Needs in Medicaid and the Children’s Health Insurance Program.” Center for Medicaid &

CHIP Services (Nov. 2023), available here.

28 Patients with children may require childcare during the patient journey. See Ranji U, Rosenzweig C, Gomez I. “Executive

Summary: 2017 Kaiser Women’s Health Survey,” Kaiser Family Foundation (2018), available here. Within this survey, 17% of women at less than 200% of FPL reported going without or delaying care due to problems with childcare.

https://www.medicaid.gov/sites/default/files/2023-11/cib11162023.pdf https://files.kff.org/attachment/Executive-Summary-2017-Kaiser-Womens-Health-Survey transplant for SCD) can be very important for patients as they consider whether gene therapy is the right choice for them, as well as during and after the treatment regimen.

Patients opting for gene therapy provide their consent to move forward with the treatment regimen.

health worker (CHW) services

4. Transition

Disease

Management to

Preparation for

Gene Therapy

(60-90 days /

Outpatient)

Patient is managed by a hematologist who specializes in SCD. Patient is gradually taken off hydroxyurea and begins chronic transfusion therapy for 2-3 months, while SCD continues to be managed.

• Access to a hematologist who specializes in SCD

• Timely access to NEMT

• Access to care coordination/patient navigation/CHW services

5. Apheresis

(3-9 days /

Inpatient)

Patient travels to transplant center for apheresis

(harvesting cells). Patients require 1-3 cycles of cell collection, each of which takes 3 days.

• Access to out-of-state providers, if there is no qualified SCD gene therapy provider (or no capacity) in the state

• Access to hematologists and transplant physicians who specialize in SCD

• Timely access to NEMT

• Access barriers, including childcare

• Access to peer counseling and support

• Access to mental health providers and health care providers specializing in pain management and addiction

• Access to care coordination/patient navigation/CHW services

6. Stem Cell

Modification

(~40-180 days /

Home)

Patient returns home while Manufacturer modifies stem cells. Manufacturers can take anywhere from 6-16 weeks to modify the cells and send them to the transplant center. During this time, a hematologist must continue to manage the patient’s sickle cell disease.

• Access to a hematologist who specializes in SCD

• Access barriers

• Access to peer counseling and support

• Access to mental health providers and health care providers specializing in

• Access to care navigation/CHW services

7. Optional

Fertility

Preservation

(Duration may take several months; typically concurrent with stem cell modification /

Outpatient)

Fertility Preservation typically takes place while waiting for the genetically modified cells to be sent back to the transplant center. Fertility

Preservation consists of harvesting, freezing, and storing reproductive material. The time required to collect reproductive material differs for males and females, and from individual to individual.

Treatment requires coordination between the patient’s fertility, transplant, and SCD specialists.

• Access to fertility preservation services

• Coordination between the patient’s fertility, transplant, and SCD specialists

• Access barriers

• Access to care coordination/patient navigation/CHW services

8. Chemotherapy

(7-9 days /

Inpatient)

Patient returns to transplant center for conditioning (chemotherapy). Before infusion of the gene therapy, the patient receives intense chemotherapy (4-6 days of receiving infusions, followed by three days of rest) on an inpatient basis.

The conditioning chemotherapy typically renders an individual infertile and results in significant mucositis, low blood counts, and fever.

• Access to out-of-state providers, if there is no qualified SCD gene therapy provider (or no capacity) in the state

• Timely access to NEMT

• Access barriers, including childcare

• Access to mental health providers and health care providers specializing in pain management and addiction

• Access to care coordination/patient navigation/CHW services

9. Gene Therapy

Infusion and

Recovery

(35-45 days /

Inpatient)

Modified stem cell product infusion occurs in hospital, followed by an inpatient stay, all of which lasts 35-45 days, during which time the patient receives frequent blood tests and assessments of lung and heart function, echocardiogram, CT scans, red blood cell and platelet infusions, bone marrow assessments, and pain management services.

• Access to out-of-state providers, if there is no qualified SCD gene therapy provider (or no capacity) in the state

• Timely access to NEMT

• Access barriers, including childcare

• Access to mental health providers and health care providers specializing in

• Access to care navigation/CHW services

10. Follow-up

Care

(15 years /

Outpatient)

Follow-up care. For the first 60 days after discharge, patient follow-up may consist of twice-weekly blood work, as determined by a hematologist. Some patients may require more intense follow-up that requires them to stay near the transplant center during this time.

100 days after the infusion, the frequency of follow-up visits may be reduced to monthly for the next year and at least annually for 15 years after infusion.

If the transplant team is not the hematologist/SCD specialist, patients require ongoing close follow-up by their SCD specialist. Follow-up care includes weaning opioid medications in the first-year post-treatment, monitoring for SCD complications that might not be eradicated long-term (e.g., stability or progression of existing organ damage), and mental health support (including peer counseling).

• Access to hematologists specializing in SCD

• Timely access to NEMT

• Access barriers, including childcare

• Access to peer counseling and support

• Access to mental health providers and health care providers specializing in pain management and addiction

• Access to care coordination/patient navigation/CHW services

• Help navigating changes in insurance coverage

A6. Program Requirements

CMS will award Cooperative Agreements to successful Applicants to implement the Model as well as to support states that achieve performance milestones.

▪ While the Model performance period begins on January 1, 2025, Cooperative Agreement funding will not begin until July 1, 2025.

▪ Recipients may not use Cooperative Agreement funding for expenses incurred prior to July 1, 2025.

Cooperative Agreements are anticipated to conclude on December 31, 2035 (at the conclusion of the

Model performance period) or earlier if a State’s participation in the Model is terminated earlier. See

Section A4, Table 2 Relationship between Calendar Years, Model Performance Years (PYs) and

Cooperative Agreement Budget Periods (BPs).

A6.1 Model Participation

The following sections describe how States and Manufacturers of Model Drugs will participate in the

Model.

A6.1.1 State Participation

To be eligible to receive Cooperative Agreement funding for this Model, the following must occur:

1) applicant receives a Cooperative Agreement award for which this NOFO is soliciting applications, and

2) applicant signs a State Agreement.

Cooperative Agreement

States that apply for and are awarded funding under the NOFO will receive a Cooperative Agreement award from CMS. Cooperative Agreement funding will support implementation of both required and optional state activities and will be awarded to Recipients that achieve performance milestones (see

Section A6.8 Cooperative Agreement Funding Structure).

To be considered for funding under this NOFO, the State must:

• Apply to the State Request for Applications (RFA) by no later than March 14, 2025

• Apply to this NOFO by no later than March 14, 2025

• Sign a State Agreement with CMS (See Section A6.3 Legal Agreements/Cooperative Agreement

Award, Table 4, 2. CMS and State: State Participation in Model (State Agreement)) by no later than June 1, 2025

CMS encourages States to read the State RFA in full before submitting a NOFO application.

State Agreement

The State Agreement will govern each State’s participation in the Model, including the requirements of the Model (See Section A6.3 Legal Agreements/Cooperative Agreement Award). States that choose to participate in the Model without funding from CMS must respond to the State RFA and sign a State

Agreement, but do not need to respond to this NOFO. The Cooperative Agreement and the State

Agreement are both expected to conclude on December 31, 2035, at the conclusion of the Model performance period (see Section A6.3 Legal Agreements/Cooperative Agreement Award).

A6.1.2 Manufacturer Participation

In the Manufacturer RFA, released on March 7, 2024, CMS invited eligible manufacturers of SCD gene therapies to apply to participate in the Model. Eligible Manufacturer respondents were invited to participate in the Model pre-implementation period.

The Model pre-implementation period began May 1, 2024 and ends November 29, 2024. During the

Model pre-implementation period, CMS and Manufacturers will negotiate the standard Key Terms. If an agreement between parties is reached, then the Manufacturer must execute a Participation Agreement

(PA) with CMS before the conclusion of the pre-implementation period.

A Manufacturer that participates in the Model pre-implementation period and signs a PA by November

29, 2024 with CMS is considered a Model participant. Manufacturer requirements for participation in the

Model are as follows:

3) Participated in negotiations with CMS during the Model pre-implementation period;

4) Entered into a PA with CMS before conclusion of the pre-implementation period; and

5) Maintains compliance with the PA.

A6.2 Model Population

The Model population includes Medicaid and Medicaid expansion CHIP beneficiaries in fee-for-service and Medicaid managed care who do not have other coverage that is the primary payer for a Model Drug.

(hereinafter, “Medicaid beneficiaries”). Manufacturers and States will have the option to include separate

CHIP beneficiaries alongside Medicaid beneficiaries.

In response to the State RFA, States will specify a start date with respect to each type of beneficiary in the

Model population: Medicaid beneficiaries enrolled in fee-for-service (Model Performance Period Start

Date); Medicaid beneficiaries enrolled in managed care plans (Managed Care Start Date); and separate

CHIP beneficiaries (separate CHIP Start Date, if applicable). See the State RFA, released on June 28, 2024, for more information.

Model beneficiaries are beneficiaries in the Model population who are deemed eligible for (i.e., are clinically eligible for and meet all negotiated prior authorization criteria) and receive a Model Drug that is covered and paid for by either: (1) a participating State Medicaid program as a covered outpatient drug where Medicaid was the primary payer; or (2) if the Manufacturer and State engage in a separate VBP arrangement for separate CHIP beneficiaries, a separate CHIP that participates in the Model.

A6.2.1 Children’s Health Insurance Program (CHIP)

Participation with respect to beneficiaries in Title XXI-funded Medicaid expansion CHIPs (i.e., CHIPs in which the State receives Title XXI funding to expand Medicaid eligibility to optional targeted low-income children) is required. All requirements for Medicaid beneficiaries in this NOFO apply to both

Title XIX-funded Medicaid and Title XXI-funded Medicaid expansion CHIPs.

Participation with respect to beneficiaries in separate CHIPs is optional for Manufacturers and States.

CMS and Manufacturers may, during Key Term negotiation, structure supplemental Key Terms that constitute a VBP arrangement that meets the definition of such an arrangement at 42 CFR § 447.502

(hereinafter, “separate CHIP Key Terms”). The separate CHIP Key Terms would be distinct from the Key

Terms for Medicaid program supplemental rebates and would satisfy requirements under CMS’s existing

“multiple best price” reporting framework.

Negotiated Key Terms regarding volume rebates or guaranteed rebates, as distinct from outcomes-based rebates, will not qualify under the “multiple best price” reporting framework and may be excluded in the agreement reached for separate CHIP beneficiaries. Unless explicitly noted (or otherwise not permissible by law), all requirements regarding the Key Terms discussed throughout the State RFA must apply to any agreement reached for the separate CHIP population.

A6.3 Legal Agreements/Cooperative Agreement Award

The Model will include a partnership among CMS, participating Manufacturers, and participating States.

This partnership will be executed through multiple legal and contractual mechanisms. Legal relationships are enumerated in both Figure 2 and Table 4.

Figure 2: Legal Agreements/(optional) Cooperative Agreement Award

Key: CMS = Centers for Medicare & Medicaid Services, MFR = Manufacturer

Table 4: Legal Agreements/Cooperative Agreement Award

1. CMS and Manufacturer: Manufacturer Participation in Model (Participation Agreement)

Anticipated Effective Dates: No later than January 1, 2025 – December 31, 2035

Description:

1) Formalizes Manufacturer Participation in the Model.

2) Specifies “Key Terms” negotiated with CMS, which will be included in the OBAs established with participating States. Key Terms may address, but are not limited to:

a. Duration of OBA Term, Measurement Period, Volume Accrual Period, and

Reconciliation Period

b. Pricing related to Outcome-Based Rebates, Guaranteed Rebates, Volume-Based Rebates

c. Outcome Measures and Outcome Measure Benchmarks

d. Fertility Preservation Services

e. Access Policy

f. CMS Responsibilities

g. Rebate Documentation

h. Termination, Renewals, Renegotiation or Alterations

i. Coverage Shifts

3) Specifies terms of CMS and Manufacturer data exchange.

4) Specifies terms of potential Model renewal.

2. CMS and State: State Participation in Model (State Agreement)

Anticipated Effective Dates: January 1, 2025*** – December 31, 2035

Description:

1) Formalizes the terms of State participation in the Model.

2) Requires States to include Medicaid beneficiaries in the Model when Medicaid is the primary payer for a Model Drug. Beneficiaries enrolled in fee-for-service Medicaid must be included by the beginning of the Model Performance Period. Beneficiaries enrolled in Medicaid managed care plans must be included by no later than January 1, 2026.

3) Allows States to include separate CHIP beneficiaries in the Model by no later than January 1, 2026, subject to separate, optional agreement with Manufacturers.

4) Establishes State requirements for Model participation. For instance, States must:

a. Have or obtain the necessary authority to implement the Model, including CMS approval of a SPA to enter into a VBP SRA.

b. Establish a standardized Model Drug access policy consistent with the CMS-

Manufacturer negotiated Key Terms.

c. Carve Model Drugs out of an inpatient payment bundle, if necessary, and pay for the

Model Drugs in a manner such that rebates under the MDRP apply.

d. Require providers to follow Model-specific requirements related to registry participation and claims submission.

e. Ensure that applicable Medicaid managed care plan policies align with Model requirements.

f. Execute a VBP SRA with a participating Manufacturer that incorporates the CMS-

Manufacturer negotiated Key Terms.

g. If applicable, execute a VBP agreement for separate CHIP beneficiaries with a participating Manufacturer that incorporates the CMS-Manufacturer negotiated separate

CHIP Key Terms.

h. Attest that included beneficiaries will have access to gene therapy care with at least one qualified SCD gene therapy provider within the state or in another state.

i. Attest that the State will ensure necessary transportation and related travel expenses to

Model beneficiaries (and their caregivers, as applicable).

j. Meet minimum data requirements and conduct data quality activities.

k. Submit reports to CMS on Model implementation.

*** States will sign SAs on a rolling basis following CMS acceptance of their applications (which may be submitted between

December 2024 and March 2025).

3. (Optional) CMS and State: Cooperative Agreement Funding (Cooperative Agreement

Award)

Anticipated Effective Dates: July 1, 2025 – December 31, 2035

Description:

1) Outlines funding for activities related to Model implementation (e.g., data collection, coordination with managed care plans and out-of-state providers, partnerships with community-based organizations, etc.).

2) Describes performance milestones for which states may receive funding related to increasing access to SCD gene therapy and promoting multi-disciplinary, comprehensive care for beneficiaries who are considering or receiving SCD gene therapy.

4. Manufacturer and State: Outcomes-Based Agreement (Value-Based Purchasing

Supplemental Rebate Agreement)

Anticipated Effective Dates: January 1, 2025* – December 31, 2030**

Description:

1) Formalizes all supplemental rebates as negotiated by CMS and the Manufacturer.

2) Specifies “Key Terms” negotiated by CMS and the Manufacturer. Key Terms may include, but are not limited to:

a. Duration of OBA Term, Measurement Period, Volume Accrual Period, and

Reconciliation Period

b. Pricing related to Outcome-Based Rebates, Guaranteed Rebates, Volume-Based Rebates

c. Outcome Measures and Outcome Measure Benchmarks

d. Fertility Preservation Services

e. Access Policy

f. CMS Responsibilities

g. Rebate Documentation

h. Termination, Renewals, Renegotiation or Alterations

i. Coverage Shifts

* May begin on a date of the State's choosing from January 1, 2025 to January 1, 2026.

** Ends at the conclusion of the OBA Term, which will be part of the Key Terms subject to CMS-Manufacturer negotiation.

5. (Optional) Manufacturer and State: Participation with respect to separate CHIP Population

(Value-Based Purchasing Agreement)

Anticipated Effective Dates: January 1, 2025* – December 31, 2030**

Description:

1) Formalizes the rebates related to the OBA as negotiated by CMS.

2) Specifies “separate CHIP Key Terms” negotiated by CMS and the Manufacturer. Separate CHIP

Key Terms may include, but are not limited to:

a. Duration of OBA…