Durable therapies: Definition

The development of transformative cell- and gene-based therapies over the past decade has raised the possibility that rare diseases with severe unmet need that are currently considered chronic or fatal may be significantly slowed down or cured after a single course of treatment. These therapies represent a foreseeable reimbursement challenge to current healthcare systems: upfront cost is substantial and is incurred all-at-once, but patient benefits are accrued over a longer period of time. If these benefits minus the costs are the basis of value, then this accrual is of significant value in a single administration event. Durability could extend for years or even a lifetime.

Expected availability to 2030

MIT NEWDIGS FoCUS has conducted a unique, detailed, indication-by-indication analysis to estimate the expected volume of durable cell and gene therapies likely to be available on the US market in the coming years. The model has been developed and refined over a period of several years, and continues to be updated on an ongoing basis.  Updated results are published periodically.

Currently there are 1,050+ active, durable, cell and gene therapies in development.  Slightly over 300 of these are product trials in China by China-based developers.  We have excluded these from the analysis to arrive at potential candidates for the US market. 6 therapies (4 individual drugs) are already approved for patient use in the US.

Figure 1: Pipeline of active programs in development for durable cell and gene therapies for the US market

Approximately 52% of product candidates in development are for oncology patients, 36% are for orphan, non-oncology indications and 12% are to treat larger therapeutic areas such as cardiovascular conditions.

MIT NEWDIGS FoCUS developed detailed estimates of clinical trial progression rates, disease incidence and prevalence, and estimated patient uptake for each product indication.

The current pipeline of US-targeted therapies is expected to result in 60+ product-indication approvals (estimated range 52-74) by 2030; with 30 approved within the next five years (by 2025).

Estimates of the associated total cost of these therapies are being updated and should be available in the Fall.

While this estimate reflects the current pipeline, the pipeline will continue to be replenished and added to with new innovations.  Thus, towards the back end of this timeframe we may see additional products launch beyond those reflected here.

Within the FoCUS model, the key uncertainty lies in the adoption rates and adoption speed for these new-to-world therapies.  The model makes assumptions about two parameters for each disease incidence and prevalence:

  • Peak penetration: What percentage of the clinically-eligible population will be treated
  • Time to peak: How long to achieve the peak (from 1 to 7 years)

Broadly, we have assumed that conditions with limited treatment alternative and more severe (fatal) consequences will see greater and faster adoption.  FoCUS will continue to explore the influence of disease severity as we have greater real-world data on patient and physician treatment choices.

While clinical trial outcomes and regulatory approvals are never guaranteed, by 2023 we expect the following types of products may be available to patients:

    Currently available

    • Oncology CAR-T therapies: Kymriah®, Yescarta®
      • Currently approved for acute lymphocytic leukemia (ALL) and diffuse large B-cell lymphoma (DLBCL)
    • Ultra-rare disease treatments
      • Luxturna® for Retinitis pigmentosa & Leber’s congenital amaurosis (both RPE65)
      • Zolgensma® for Spinal muscular atrophy

    Likely available by 2023, assuming clinical trial success

    • Oncology
      • Multiple Myeloma
      • Further therapies for B-cell leukemia and lymphoma
    • Rare Disease treatments
      • Hematological conditions
        • Hemophilia A & B
        • Sickle Cell anemia
        • Beta-thalassemia
      • Additional treatments for ophthalmological conditions
        • Retinitis pigmentosa & Leber's congenital amaurosis (other genetic mutations)
        • One or more other conditions possible
      • Neurological conditions
        • One or more probable
      • Other conditions
        • One or more probable
    • Higher prevalence disease treatments
      • Macular degeneration possible

    A synthesis of the approach used to develop these estimates may be found here.

    Note:  Research continues to advance and findings will be updated on a periodic basis.

    Therapy distinctiveness

    These products differ from traditional pharmaceutical products in that patients may benefit for a long period after the administration of therapy. This disrupts the normal payment paradigm for chronic treatments wherein reimbursement occurs in parallel with the recognition of benefits. In many ways it is a shift from a model of ‘renting’ treatments to one of ‘buying’ long-term health improvements as the following graphic illustrates.

    Figure: Therapy characteristics influencing precision financing needs

    Paying for the full value of the treatment upfront creates a number of challenges, resulting from:

    • Uncertainty about real world benefits (uncertainty about the benefits in a broader, real world population and the duration of those benefits given limited clinical trial data for this new area of science);
    • Potential disconnects between who pays and who benefits (due to the potential for patients to change insurance plans over time after they have received treatment); and
    • Difficulties in paying for the full value of the treatment upfront (particularly for smaller payers for whom patients may be infrequent and who may have a smaller population base over which to spread the higher upfront treatment costs).

    While all therapies will have these challenges, individual products in the broad category of durable, transformative cell and gene therapies have different profiles and characteristics that affect the need for various precision financing solutions.

    size size size size size size

    Figure: Therapy characteristics influencing precision financing needs

    Size of target population

    The incidence and prevalence of each therapy’s target population will vary and affect total treatment expenditures. Incidence reflects the number of new patients with a condition in a given year. Prevalence reflects the total population with a particular condition. Some conditions with high mortality rates only have an incident population. A large prevalent population could mean that a large number of patients are waiting for a transformative treatment. While we do not know what therapy uptake will be, a significant prevalent population could increase the annual total cost of treatment in the short-term until a condition again only has an annual incident population needing treatment.

    Nature of clinical benefit

    For the eligible population, durable (curative) therapies will vary in their clinical benefit relative to existing standards of care across multiple dimensions, including:

    • The nature of their expected benefit: Expected benefit could range from a “cure” that eliminates all symptoms and modifies all condition processes, to modest reversal or slowdown of selected disease processes over a shorter period of time.
    • The likelihood and severity of adverse events.
    • Heterogeneity of patient response: Patients do not all respond to treatment the same way and to the same extent. There may be non-responders, partial responders, and complete responders and that mix may vary by therapy.
    • The clinical benefit compared with alternative treatment options.

    Offsetting and mismatched benefits

    Durable therapies will vary in their net financial impact to the healthcare system, to society and to patients and their caregivers. Some therapies may reduce other healthcare treatment and service spending, while also generating higher patient benefit. Other therapies for conditions that generate relatively low costs due to rapid death or absence of treatments for chronic morbidity reduction may increase overall healthcare spending while generating patient benefits. Those benefits may reduce other social program costs and create additional economic benefits.

    In addition, the timing of financial impact may vary; some treatments could result in immediate healthcare savings, while others could save money over time. For those therapies that save money over time there could be a mismatch between who pays for the therapy and who reaps the benefits of the patient having had that therapy, as patients may switch payers over time.

    Durability of effect

    Efficacy duration will vary among patients for a single therapy and across therapies in general. Some may experience a lifetime of benefit, but many patients may not. In addition, the full duration of effect for a particular treatment will not be known at the time of initial regulatory approval and launch, due to the urgent need in some cases of getting the treatment to the patients, and the fact that this is a new area of science not yet tested over generations.

    Therapeutic modality

    Some cell and gene therapies employ viral vector delivery of genetic material in vivo while still others are similar to advanced transplantation with cellular harvest, ex vivo transfection and expansion, followed by cellular re-introduction. Therapeutic modality affects the location of treatment, payer benefit classification, provider reimbursement mechanisms, and patient financial participation, which in turn affects the financial challenges these therapies generate.

    Delivery setting

    Durable (curative) treatments vary in where the therapy is administered. Products may be administered within the inpatient or outpatient setting and at a limited number of centers of excellence or a broader set of facilities. Some therapies may require extended hospitalization stays or intensive follow-up, while others may warrant only periodic clinic follow-up.

    These characteristics not only affect the stakeholders requiring financial solutions but also impact ecosystem-related operational enablers such as appropriate provider networks, certifications, care coordination, product distribution and data monitoring processes to ensure patients have access or financial solutions can be administered or both.

    Critical precision financing dimensions

    Durable, potentially curative therapies create three financial challenges:

    1. Payment timing: Therapies can involve substantial upfront payment for multiple years of therapeutic benefit.

    2. Therapeutic performance risk: Real world efficacy and durability are uncertain at the time of initial regulatory approval and market launch.

    3. Actuarial risk: The number of eligible patients in a payer’s population may be uncertain and could vary significantly from period to period.

    Payers will not all be equally affected by these therapies and risks. US payers differ in terms of number of covered lives (size), types of lives covered (children, elderly, mixed), funding sources (self-funded, premiums, taxes), and the coverage and reimbursement rules that they must follow. They will not be equally affected by the above risks. For example, Medicare and larger commercial insurers face less actuarial risk than self-insured employers, regional commercial plans, and some state Medicaid plans due to the significantly larger number of lives they cover. Financial solutions addressing actuarial risk may therefore be needed and appropriate for only smaller payers. Similarly, some payers may cover clusters of patients with certain genetically-driven conditions that occur in families and therefore have a larger number of members who might benefit from a particular therapy than other payers.

    Self-assessment of financing needs

    As precision financing needs will differ by product and payer characteristics, the FoCUS team has developed a simple Solutions Prioritization Tool for those who wish to understand what solutions FoCUS stakeholders have prioritized for particular product and payer types and risks. Further drill down into each solution is possible, once identified.

    In addition, for those considering how to address the overall pipeline of cell and gene therapies or an individual therapy, Payers’ Guided Assessment Tools for Individual Indications and the Pipeline are available.

    An overview of all precision financing solutions fleshed out by FoCUS can be found here and an overview of other solution design considerations may be found here.