Author: Liao Lianming, associate researcher of Union Hospital Affiliated to Fujian Medical University
introduction
In January 2024, the Center for Medicare and Medicaid Innovation (CMMI) released the Cell and Gene Therapy Access Model. Under this model, U.S. state providers would have carte blanche to entrust CMMI to negotiate additional rebates on their behalf with manufacturers for cell and gene therapy products. The model aims to explore whether commercial agreements based on efficacy outcomes developed by CMMI for novel cell and gene therapies can improve accessibility and equity while reducing Medicaid spending. This paper compiles the relevant literature, which will have certain reference significance for how to solve the problem of the accessibility of high-priced drugs in mainland China while ensuring the reasonable return of R&D pharmaceutical companies.
Recently, Kannarkat and others from the University of Maryland in the United States wrote an article in JAMA discussing the role of the Biden administration in promoting the use of novel cell and gene therapy methods. This model was introduced to address the issue of access to sky-high prices of drugs and to try to reduce healthcare costs.
The article points out that in January 2024, the Center for Medicare and Medicaid Innovation (CMMI) released the "Cell and Gene Therapy Access Model". Under this model, U.S. state providers would have carte blanche to entrust CMMI to negotiate additional rebates on their behalf with manufacturers for cell and gene therapy products. The model aims to explore whether commercial agreements based on efficacy outcomes developed by CMMI for novel cell and gene therapies can improve accessibility and equity while reducing Medicaid spending.
Notably, this model links drug rebates to actual efficacy outcomes after treatment, which is a value-based payment method that will incentivize manufacturers to focus not only on drug development and sales, but also on the effectiveness of the drug in practical applications. There are comments that the implementation of the model will also have a positive impact on medical institutions in the states. Through the unified consultation of CMMI, states can share resources and experience to negotiate more effectively with drug manufacturers, helping to reduce the procurement costs of medical facilities in each state.
However, the implementation of this model also faces a number of challenges. How to ensure the objectivity and fairness of efficacy evaluation, how to balance the interests of manufacturers and medical institutions, and how to ensure the transparency and sustainability of the rebate mechanism need to be continuously explored and improved in practice.
At present, five gene therapies with a price of more than $2 million have been approved worldwide. The most expensive drugs, Hemgenix, a hemophilia drug from CSL Behring and uniQure, cost $3.5 million each. Due to price issues, the sales of many sky-high drugs in 2023 are not ideal. Only Elevidys, the gene therapy for Duchenne muscular dystrophy (DMD), has sales of more than $1.4 billion in 2023, and the drug is priced at $3.2 million per dose, making it the second most expensive drug in the world.
Gene defects account for 80% of more than 7,000 rare diseases in the world, and gene therapy is the only effective and lifelong cure for this field, bringing hope to families of rare disease patients. However, the payment for these rare diseases has become an unbearable burden for patients and their families.
How to balance the interests of drug developers and patients has become a common problem faced and solved by the whole society. Governments must therefore be actively engaged and play a central role in addressing this challenge.
This paper is compiled as follows, which will have certain reference significance for how to solve the problem of accessibility of high-priced drugs in mainland China while ensuring reasonable returns for R&D pharmaceutical companies.
Compiled by Liao Lianming
Commercial agreements, especially those based on the clinical efficacy of a drug, are a form of contract between a U.S. paying institution (e.g., Medicaid) and a drug manufacturer, and at its core, closely link the rebate of the drug to the actual efficacy after treatment is initiated.
Cases of sickle cell disease
The first disease to be addressed in this new protocol is sickle cell disease (SCD). Up to now, only two gene drugs have been approved for the treatment of SCD in the world. One is Blue Bird Bio's Lyfgenia, which is priced at $3.1 million per patient; The other is CRISPR Therapeutics and Vertex Pharmaceuticals' Casgevy, which is priced at $2.2 million per patient. Both use gene-editing methods, but the principle of action is not the same. Ligevy is a modified protein that increases fetal hemoglobin expression, while Lyfgenia is a modified protein that increases normal adult hemoglobin A.
As a disease included in a commercial agreement, SCD is undoubtedly a wise choice. In the U.S., about 50%-60% of patients with SCD rely on Medicaid to maintain treatment, and the high cost of care for SCD puts a heavy financial strain on Medicaid providers and stretches budgets. This agreement is expected to improve access and equity for SCD patients while reducing healthcare costs through innovative payment methods.
In cases where drug manufacturers and Medicaid agencies are voluntary, CMMI will first negotiate with interested manufacturers the details of the agreement based on efficacy outcomes, including outcome metrics, rebate percentages, and more. The efficacy-based outcome protocol will be available to patients with SCD who participate in a state program, Medicaid, or Children's Health Insurance Program, CHIP, with Medicaid or CHIP as the primary payer.
CMMI intends to promote a uniform agreement based on efficacy outcomes among states to increase their bargaining power with manufacturers. To ensure the effective implementation of this plan, CMMI will also provide financial and technical support to the states to help them better participate in the consultation process.
Addressing challenges among stakeholders
With most previous models targeting clinicians for payment, CMMI faces new challenges in drug procurement reform, particularly in selecting efficacy metrics, understanding Medicaid patient characteristics, promoting equity, and encouraging stakeholder engagement. However, CMMI is expected to successfully address these challenges and provide better and more efficient healthcare services to patients.
The outcome-based protocol will have additional rebates based on the actual effectiveness of the product for the patient. This is calculated based on predetermined efficacy outcomes in the protocol.
CMMI will select those indicators that can reliably reflect the effectiveness of the drug, and the indicators should not be too cumbersome, but not too single, and in the process, how to develop efficacy standards is full of challenges. For example, clinically value-based efficacy outcomes for SCD include patient mortality, disease-specific blood markers, use of other treatments such as treatment of episodes of vascular occlusion, SCD-related hospitalizations and emergency department visits, and patient-reported outcomes such as function, pain, and quality of life.
However, clinical trial blood markers are not routinely tested by clinicians, and they do not represent meaningful clinical outcomes for patients. With recourse reimbursement data, we may be able to extrapolate the approximate efficacy of the drug.
In addition, patient-reported outcomes only reflect patient-important outcomes, and manufacturers are skeptical of the subjectivity of patient-reported outcomes, making it difficult to collect patient-reported outcomes. In addition, the duration of the model (≤11 years) and the time required to assess improved outcomes (2 years based on clinical trial experience) conflicted with the immediacy of Medicaid reimbursement.
Regardless of the outcome, CMMI and states will need to first build a robust hardware and software system to gather relevant information and a robust mechanism to enforce the terms of the agreement based on efficacy outcomes before selecting any option.
In addition to the drug price itself, under this model, manufacturers may work with Medicaid, clinicians, and patients to provide a comprehensive range of services to further improve efficacy. For example, manufacturers will be willing to spend money to provide effective integrated services, improve medication adherence and appointment rates, improve the efficacy of gene therapy, and obtain a higher proportion of payment.
CMMI will need to have appropriate incentives in place to ensure that manufacturers and states are willing to participate. Even though ensuring that there is a high level of patient participation and the need to negotiate with states separately may incentivize manufacturers to participate, manufacturers will consider issues such as treatment outcomes and rebate structures in their decision-making. Under the Medicaid drug rebate program, manufacturers are willing to pay additional rebates to states for bonuses such as placement on the priority drug list.
Under the outcome-based agreement, the manufacturer will pay an additional supplemental rebate tied to the efficacy outcome in exchange for the drug being included in Medicare.
Then, these supplementary rebates can also be detrimental to the pharmaceutical company, and if the efficacy is not good, the manufacturer will pay more rebates to the health insurance department. After all, the treatment method is new, and the clinical trials before the market only have short-term efficacy data, and the manufacturer does not know the duration of the treatment effect; Moreover, the sample size of clinical trials before marketing is small and cannot represent real-world efficacy. For patients who are partially ineffective, CMMI can mandate free retreatment, which may also lead to reluctance from the manufacturer to participate.
On the other hand, different states have different attitudes towards the introduction of results-based protocols by CMMI. Some states may think that they can earn more rebates by negotiating with manufacturers through CMMI. Other states may find management and coordination cumbersome and therefore reluctant to participate in CMMI. For example, in 2019, only 31 states participated in drug purchase agreements; 4 of the 5 most populous states did not participate.
Nonetheless, the lessons learned from this model of CMMI will have far-reaching implications for future health policies oriented towards drug reform. These experiences not only help us better understand how to balance the relationship between drug cost, efficacy and patient accessibility, but also provide valuable references for the development of more rational and effective health policies. Therefore, whether states choose to participate or not, the implications of this model will be of inestimable value to the field of health policy.
Citation：Kannarkat JT, Hernandez I, Parekh N.
Advancing Access to Cell and Gene Therapies in Medicaid. JAMA. Published online May 22, 2024. doi:10.1001/jama.2024.6224
About the Author
Liao Lianming, Ph.D., associate researcher of Union Hospital Affiliated to Fujian Medical University, master's supervisor, mainly engaged in mesenchymal stem cell biology and application research. He is a member of the editorial board of the Chinese Journal of Cell and Stem Cell and the editorial board of the Journal of Vascular Investigation and Therapy. Associate Editor-in-Chief of Journal of Biomaterials and Tissue Engineering. He has published more than 180 SCI papers. He has participated in stem cell related research papers published in internationally renowned journals, including "Bone Marrow Transplantation", "Diabetes", "JAMA", "JCO", "Cytotherapy", etc. He is a standing member of the second editorial board of the special issue of stem cell and regenerative medicine of Medical Information Daily, and a member of the stem cell engineering professional committee of the Medical Engineering Branch of the Chinese Medical Association.