Assessing the Value of Non-Curative Cell and Gene Therapies

Published October 6, 2021

Executive Summary

• Given the majority of cell and gene therapies to date have offered the potential of a cure, pricing and access considerations are likely to differ for non-curative agents that are entering this space
• Although non-curative cell and gene therapies have demonstrated clinical efficacy (e.g., for multiple myeloma and wet age-related macular degeneration), manufacturers will need to communicate additional value offerings of these therapies to payers in order to avoid pushback and enhance access potential, such as:
  • Robust evidence of long-term and sustained clinical benefits for patients
  • The potential for cost-offsets (e.g., a reduction in the frequency of infusions)
  • Enhanced patient convenience
  • Pricing strategies for non-curative therapies may be constrained by a lower willingness-to-pay vs. “one-and-done” treatments

Trinity’s Take: Manufacturers should prioritize refining and tailoring their value messaging to communicate the incremental value that their therapy provides over current treatments, optimize their pricing strategy based on the cost-offsets their product generates, and pursue contracting strategies to maximize access.

Introduction to Cell and Gene Therapies

Cell and gene therapies are innovative treatments with disease modifying properties that can treat a range of conditions such as genetic disorders and cancers. By addressing the root cause of a disease through the introduction of live cells or genetic material, these treatments have shown high rates of complete response in some cancers as well as the complete reversal of debilitating genetic conditions; this has led to them being perceived as “curative” therapies.

This promise of cure for diseases with high mortality rates or severe lifelong disability has been used to justify the substantial prices of these cell and gene therapies. Such is the case of ZOLGENSMA, which has been approved for use across Europe and the USA for the treatment of spinal-muscular atrophy (SMA). A single infusion with this gene therapy in children under two years can both prevent mortality and prevent a decline in motor outcomes, proving its value as a “one and done” treatment. This therapy carries a USD 2.1 million price tag at the list level in the USA and a retail price of EUR 2.2 million in ITA for example.

However, not all cell and gene therapies hold the same promise. that are capable of inducing a strong response and decrease the need for frequent treatment, but they may still require more than one administration, fail to cause permanent remission of certain cancers, or fail to fully correct issues associated with genetic abnormalities. Clearly, this will impact the clinical value proposition for these treatments and subsequently, payer decision making.

In a landscape where even curative cell and gene therapies are facing challenges (e.g., ZYNTEGLO withdrawal from DEU), manufacturers need to carefully design a value strategy for their non-curative assets to ensure maximum access and uptake in their target markets.

Current and Pipeline Non-Curative Cell and Gene Therapies

Some cell and gene therapies without a curative promise have shown encouraging results for patients with chronic disorders. One example is Adverum’s ADVM-022, a gene therapy for wet age-related macular degeneration. This is a disorder resulting in irreversible loss to the patient’s central vision, for which current treatment involves lifelong intravitreal injections of VEGF inhibitors. ADVM-022 is formed of an adeno-associated virus vector encoding the VEGF inhibitor aflibercept and provides sustained anti-VEGF levels in the retina with a single injection – reducing the need for regular aflibercept administrations. The drug’s ability to demonstrate treatment durability of over 15 months through its OPTIC trial has led to a fast-track designation by the FDA.

Notable developments have also been seen in the oncology space, with multiple myeloma CAR-T therapies showing high overall response rates in late line patients and a median duration of response of around one year. The potential to induce responses in these later lines of therapy that are more durable than what is currently available for patients highlights opportunities for these therapies to address a clinical unmet need, despite not being curative. Furthermore, the one-time administration and subsequent treatment-free interval of CAR-Ts in multiple myeloma drives improvements to patient quality of life as well as treatment cost savings.

Finding Value of Cell and Gene Therapies Without Cure

Without the promise of a cure, it is important that manufacturers of cell and gene therapies identify and communicate their value proposition to ensure optimal reimbursement and uptake from payers and providers.

An important value offering for some of these non-curative therapies is enhanced patient convenience – for example, in the case of ADVM-022, patients can receive a single intravitreal injection vs. repeated injections every eight weeks, potentially alleviating patient discomfort as well as issues relating to adherence. However, manufacturers need to consider environment shaping and payer education activities to ensure this value driver is recognized in and tailored to the market in question. Moreover, manufacturers must also be careful to ensure that validated quality of life measures (e.g., EQ-5D, EORTC QLQ-C30) are used to support such claims.

Evidence supporting non-curative cell and gene therapies as not only effective, but also safe options relative to current standard of care may also help to support payer acceptance of these agents. Payer concerns around mechanism of action (e.g., mutations due to integration into the genome) must be addressed to not only prove that such gene therapies are as safe as existing agents, but also to differentiate these agents from a safety perspective.

Non-Curative Cell and Gene Therapy Pricing Expectations

The high cost of cell and gene therapies more broadly have historically been scrutinized by payers and have ultimately led to various hurdles in terms of access and uptake. The perceptions of high prices that are associated with curative cell and gene therapies may be carried over to non-curative treatments, which would be challenged given they do not offer a “one and done” treatment mechanism.

Robust analogues for non-curative cell and gene therapies currently do not exist, resulting in a lack of appropriate price benchmarks. However, willingness-to-pay is likely to be lower compared to “one-and-done” treatments. For example, gene therapies such as LUXTURNA, which is indicated for mutation-associated retinal dystrophy had a price of USD 850,000 USD at launch; using this as a guide to price ADVM-022 could draw objections from payers, given that LUXTURNA is curative and ADVM-022 has yet to demonstrate this potential. Depending on frequency of infusions and clinical outcomes, pricing approaches for these non-curative therapies therefore might be more similar to those of conventional drugs.

Some opportunities for these non-curative therapies lie in the cost-offsets they generate, given the lower need for frequent administration of regular treatment. For example, ADVM-022’s elimination of the need for regular intravitreal injections performed by eye specialists saves the high yearly costs of aflibercept treatment. Moreover, the one-time infusion of CAR-T cells can provide multiple myeloma patients with up to a year of treatment-free life, which incurs cost savings to payers at least in the near-term. While USA payers may not prioritize patient convenience in their decision making, the addition of cost offsets to the value proposition could tip the balance favorably. This attribute may also be prioritized in cost-effectiveness markets such as the UK but is likely to be de-emphasized in markets that primarily focus on comparative clinical effectiveness.

Future Landscape for Cell and Gene Therapies

Overall, non-curative cell and gene therapies hold great potential as new options for the treatment of diseases given their potential improvements to efficacy and safety over the existing standard of care, which can lead to better clinical outcomes, and reduce treatment burden for patients who are subject to frequent treatment administrations.

However, despite these positives, developing and justifying pricing strategies for this new generation of treatment is likely to be challenging. Given that they do not provide a permanent “cure” for patients, it is possible that payers will expect to assess these treatments like regular drugs, meaning they are less likely to command the premium prices of currently available cell and gene therapies.

It is therefore important manufacturers refine and tailor their value messaging to communicate the incremental value that their assets provide over current treatments, and carefully design pricing and contracting strategies in alignment with these value propositions.

Written by: Jeremy Guild, Esme Norbury, and Ismail Ismailoglu, PhD