Gene therapy is emerging as a potential cure for those battling sickle cell disease, offering optimism for those affected by this debilitating condition. For this promise to be realized, however, significant barriers to access must be mitigated. In this article, we delve into challenges faced by vulnerable populations in accessing cell and gene therapies and explore potential solutions.

Sickle Cell Disease & Treatment Options Today
Sickle cell anemia is a genetic disorder characterized by misshapen red blood cells, causing them to become rigid and crescent-shaped. This irregularity disrupts blood flow in blood vessels, leading to severe pain crises and organ damage. With limited curative opportunity, it is a lifelong condition for most with challenging symptom management, morbidity and early mortality.[1] For example, among the approximately two-thirds of sickle cell patients covered by Medicaid in particular, 64% of patients demonstrate a least one hospitalization due to sickle cell disease annually, and the average length of hospital stay is approximately 13 days.[2][3] Overall, hospital stays can cost thousands to hundreds of thousands of dollars a year depending on hospital admission driver or health complication.[4]

Sickle cell disease management requires disease state fluency, chronic access to appropriate medical care & treatment options, and long-term adherence to medication schedules.[5] Hydroxyurea is the baseline standard of care for early symptom prevention, increasing production of fetal hemoglobin and reducing the likelihood of red blood cell sickling.[6] Other disease-modifying treatment options, such as L-glutamine, voxelotor, and crizanlizumab, work to improve red blood cell health, reduce sickling and limit the potential for cells to stick together, respectively.[5][7][8][9] Blood transfusions and pain management medications are also common approaches to alleviate symptoms.[5]

Options to address the underlying condition are currently limited to hematopoietic stem cell transplantation (HSCT) and gene modifying therapies in clinical trials.[10] HSCT is less common due to the limited availability of stem cell donors and, though increasingly less frequent, risks of severe side effects or death.[11][12] Alternatively, gene therapies offer unique hope for sickle cell patients given the potential for increased availability (i.e., patient cell reliance vs. donor reliance) and fewer side effect risks.

Access to Care Challenges in Sickle Cell Disease
Sickle cell disease presents a unique set of challenges that make it notoriously difficult to treat effectively. Accessing adequate treatment is quite burdensome and can seem like an insurmountable task to some, due to reasons that include but are not limited to specialist availability, burden of adherence, and variability in patient coverage requirements.

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  • Specialist Availability: Specialized sickle cell treatment centers are typically located in urban centers in the US, and nearly 30 states have either one specialized center or lack a specialized center entirely.[13] This can result in significant travel burdens for families that lack reliable transportation or family care availability.
  • Burden of Adherence: Limitations in accessibility of disease state education on the importance of medication adherence combined with transportation and family care support required for chronic treatment challenge the ability for patients to adhere to treatment regimens.[5] Among a sample of Medicaid patients, for example, nearly 60% of patients discontinued hydroxyurea over the course of 1 year.[3]
  • Variable Payer Management of Sickle Cell Disease: Fragmentation in Commercial & Medicaid payer coverage, in the US in particular, muddies clinician transparency into in-network status, coverage requirements and the extent to which patients have coverage for care. For example, eligibility criteria for treatment coverage often include different permutations of requirements such as prior therapy failure specifications (e.g., types tried, duration of treatment, adherence), number of annual pain crises or number of annual ER visits/hospitalizations.
  • Delayed Medicaid State Consensus on Coverage Requirements: Medicaid has been historically slower to develop and publicly release coverage policies for new-to-market products (e.g., 6-12 months). During this time period, provider uncertainty of coverage requirements and one-off case approvals via medical exception processes extend the time until coverage approval of patient cases following approval by the U.S. Food and Drug Administration (FDA).

Access to Care Challenges for Gene Therapies
While the science behind gene therapy for sickle cell anemia is compelling, added logistical and financial barriers impact accessibility of treatment. More unique challenges to gene therapy include frontloaded care, patient & caregiver affordability of the treatment journey, and provider site affordability of offering care.

  • Unique, Front-Loaded Treatment Journey: Differing from daily or periodic treatment options in the standard of care, gene therapies require more frequent and extended physician site visits upfront and until the point of treatment administration.
  • Patient & Caregiver Affordability of Treatment Journey: Given that treatment centers offering sickle cell disease gene therapy are likely to be dispersed across select sickle cell specialized centers around the country, similar transportation issues will be present. Additionally, however, the front-loaded treatment journey will concentrate patient & caregiver out-of-pocket costs upfront and may also require an extended stay near the hospital.
  • Payer Affordability of the Treatment Journey: As the US healthcare system is built around chronic condition management with annualized budgets and patients changing health plans every few years, transitioning toward one-time treatments is financially challenging to manage for insurance companies.[14] While a relatively limited set of patients are treated with high-cost one-time treatments to date, sickle cell disease impacts a larger population and payers may feel more straining on annual budgets. Ex-US, payers see affordability concerns with budget allocation toward rarer conditions vs. greater population health drivers; this has driven a greater focus on outcomes-based payment models.
  • Hospital Affordability of Offering Care: While Commercial insurance typically covers the costs associated with gene therapy and other treatments, Medicaid reimbursement sustainability for gene therapy can vary at the state level. Medicaid bundled payment structures for episodes of care can result in the application of a fixed reimbursement amount to products and services rendered that fall far below the list price of the product. While select states (e.g., CA, NY, MA) have started carving cell and gene therapies out of standard reimbursement structures, most other states have yet to follow suit.[15][16][17] This degree of reimbursement risk can limit a hospital’s ability to offer gene therapy to Medicaid patients from states with more challenging reimbursement models.

Gene Therapy Access Support Needs & Opportunity
Though access challenges in sickle cell disease and gene therapy treatment may pose discouraging, there are a number of opportunities to mitigate these issues with strategic planning, service offerings and appropriate resources. The Cell & Gene Therapy Practice at The Dedham Group, a subsidiary of Norstella, is well-versed in pre-launch planning needs for novel therapeutics. We support pharmaceutical companies and biotechs in preparing for payer, provider, advocacy group and patient engagement activities to mitigate market access challenges.

Examples of opportunities to improve access include, but are not limited to:

  • Motivating More Medicaid States to Carve-Out Gene Therapy Reimbursement: Driving greater awareness of gene therapy carve-outs in both the Medicaid channel and among payer contracting teams may help move the needle in more states.
  • Ensuring Payer Clarity on Eligibility to Reduce Case Approval Delays: Ensuring payer channel understanding of appropriate coverage criteria for the new product, based on FDA label and any relevant clinical trial criteria, can limit implementation of clinically inappropriate population-limiting access restrictions. Clarity on eligibility is also supported by unmet need in the target population, product role in the evolving standard of care, differentiation in the mechanism of action vs. alternative treatment options, efficacy, safety, and potential budget impact.
  • Training Provider Sites on Clinical, Operational, Economic & Access Needs: Empowering provider sites to have clinical and operational preparedness to safely administer care (e.g., training, care & scheduling best practices, necessary third-party contracts, technology platforms, etc.), fluency in reimbursable steps and associated billing & coding for sustainable reimbursement, and clarity on patient medical history details that will need to be provided to payers for rapid, appropriate patient coverage can streamline appropriate patient treatment initiation.
  • Driving Support Offering Awareness: Improving awareness of support services available across payers, advocacy groups/foundations, hospitals, and pharmaceutical companies, including case managers and education resources, as well as transportation, lodging & meal support for eligible patients can reduce the extent of resource barriers to care.

In conclusion, the potential of cell and gene therapies to revolutionize the treatment of diseases like sickle cell anemia is tremendous. However, realizing this potential hinges on our ability to break down the barriers currently hindering access for vulnerable populations. As we navigate the complex landscape of insurance coverage, healthcare infrastructure, and socioeconomic & geographic disparities, it is essential to remember that equitable access to these life-saving therapies is not only a matter of medical progress but also a moral imperative.

Perspective provided by Jen Klarer, Partner and Head of the Cell & Gene Therapy business unit at The Dedham Group, a Norstella Company. Let’s connect. We can help!

[1] Abboud MR. Standard management of sickle cell disease complications. Hematol Oncol Stem Cell Ther. 2020 Jun;13(2):85-90. doi: 10.1016/j.hemonc.2019.12.007. Epub 2020 Mar 12. PMID: 32202245.
[2] Grady A, Fiori A, Patel D, Nysenbaum J. Profile of Medicaid enrollees with sickle cell disease: A high need, high cost population. PLoS One. 2021 Oct 27;16(10):e0257796. doi: 10.1371/journal.pone.0257796. PMID: 34705847; PMCID: PMC8550393.
[3] Shah N, Bhor M, Xie L, Halloway R, Arcona S, Paulose J, Yuce H. Treatment patterns and economic burden of sickle-cell disease patients prescribed hydroxyurea: a retrospective claims-based study. Health Qual Life Outcomes. 2019 Oct 16;17(1):155. doi: 10.1186/s12955-019-1225-7. PMID: 31619251; PMCID: PMC6794855.
[4] Baldwin Z, Jiao B, Basu A, Roth J, Bender MA, Elsisi Z, Johnson KM, Cousin E, Ramsey SD, Devine B. Medical and Non-medical Costs of Sickle Cell Disease and Treatments from a US Perspective: A Systematic Review and Landscape Analysis. Pharmacoecon Open. 2022 Jul;6(4):469-481. doi: 10.1007/s41669-022-00330-w. Epub 2022 Apr 26. PMID: 35471578; PMCID: PMC9283624.
[5] Treadwell MJ, Du L, Bhasin N, Marsh AM, Wun T, Bender MA, Wong TE, Crook N, Chung JH, Norman S, Camilo N, Cavazos J, Nugent D. Barriers to hydroxyurea use from the perspectives of providers, individuals with sickle cell disease, and families: Report from a U.S. regional collaborative. Front Genet. 2022 Aug 26;13:921432. doi: 10.3389/fgene.2022.921432. PMID: 36092883; PMCID: PMC9461276.
[6] Hydroxyurea for Sickle Cell Disease Treatment Information from the American Society of Hematology (ASH). [Brochure]
[7] Center for Drug Evaluation and Research, et al. (2017b, July 7). FDA D.I.S.C.O.: L-glutamine for sickle cell disease. U.S. Food and Drug Administration. [Brochure]
[8] Yenamandra A, Marjoncu D. Voxelotor: A Hemoglobin S Polymerization Inhibitor for the Treatment of Sickle Cell Disease. J Adv Pract Oncol. 2020 Nov-Dec;11(8):873-877. doi: 10.6004/jadpro.2020.11.8.7. Epub 2020 Nov 1. PMID: 33489427; PMCID: PMC7810265..
[9] Ataga KI, Kutlar A, Kanter J, Liles D, Cancado R, Friedrisch J, Guthrie TH, Knight-Madden J, Alvarez OA, Gordeuk VR, Gualandro S, Colella MP, Smith WR, Rollins SA, Stocker JW, Rother RP. Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease. N Engl J Med. 2017 Feb 2;376(5):429-439. doi: 10.1056/NEJMoa1611770. Epub 2016 Dec 3. PMID: 27959701; PMCID: PMC5481200.
[10] Khemani K, Katoch D, Krishnamurti L. Curative Therapies for Sickle Cell Disease. Ochsner J. 2019 Summer;19(2):131-137. doi: 10.31486/toj.18.0044. PMID: 31258425; PMCID: PMC6584191.
[11] Krishnamurti L, Neuberg DS, Sullivan KM, Kamani NR, Abraham A, Campigotto F, Zhang W, Dahdoul T, De Castro L, Parikh S, Bakshi N, Haight A, Hassell KL, Loving R, Rosenthal J, Smith SL, Smith W, Spearman M, Stevenson K, Wu CJ, Wiedl C, Waller EK, Walters MC. Bone marrow transplantation for adolescents and young adults with sickle cell disease: Results of a prospective multicenter pilot study. Am J Hematol. 2019 Apr;94(4):446-454. doi: 10.1002/ajh.25401. Epub 2019 Feb 11. PMID: 30637784; PMCID: PMC6542639.
[12] Ashorobi, D., Naha, K., & Bhatt, R. (2023, July 19). Hematopoietic Stem Cell Transplantation in Sickle Cell Disease. In StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing. Online. Last accesses on September18, 2023. Available from:
[13] NASCC. (n.d.).
[14] Fang H, Frean M, Sylwestrzak G, Ukert B. Trends in Disenrollment and Reenrollment Within US Commercial Health Insurance Plans, 2006-2018. JAMA Netw Open. 2022 Feb 1;5(2):e220320. doi: 10.1001/jamanetworkopen.2022.0320. PMID: 35201308; PMCID: PMC8874349.
[15] California Department of Health Care Services. (2022). MEDI-CALD Diagnosis Related Groups Payment Method Frequently Asked Questions For State Fiscal Year 2022-23. Online. Last accesses September 18, 2023. 2022-23.
[16] New York State Department of Health. (2021, October). New York State Medicaid Fee-for-Service Policy and Billing Guidance for Chimeric Antigen Receptor T-cell Therapy. Online Last accesses on September 18, 2023.
[17] Mass Health. (2023, July). MassHealth Acute Hospital Carve-Out Drugs List. Online. Last accesses on September 18, 2023.

Featured image: Sickel Cell anemia, Peripheral blood Smear (Ed Uthman). Attribution CC BY 2.0. Used with permission

How to Cite


Jennifer Goldenberg Klarer 1
Breaking Barriers to Access: Empowering Vulnerable Populations with Cell and Gene Therapy – Onco Zine – The International Oncology Network, September 18, 2023.
DOI: 10.14229/onco.2023.09.18.011
1 The Dedham Group/Cell & Gene Therapy


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