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Groundbreaking treatment approaches call for innovative commercialization strategies.
Groundbreaking treatments involving adoptive cell transfer, such as CAR -T drugs, call for innovative commercialization strategies
The approval of the first genetically modified cell therapy in the US-Kymriah™ by Novartis-made headlines in late August of this year, receiving marketing approval in North America for the treatment of B-cell acute lymphoblastic leukemia (ALL) in children and young adults with limited treatment options. Less than two months later, Kite Pharma received approval for Yescarta™ for the treatment of adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy. Both breakthroughs are chimeric antigen receptor T-cell (CAR-T) therapies that involve adoptive cell transfer (ACT). Over the next decade, we can expect other ACT therapies to change the field of oncology dramatically, particularly in some of the more difficult-to-treat cancers.
In parallel, biopharmaceutical manufacturers of ACT therapies will need to alter their traditional commercial models just as dramatically. First, ACT therapies are not drugs in any traditional sense; rather, they are medical procedures that require individualized, ex vivo processing and highly specialized healthcare professionals and facilities. If these first two market entrants are trendsetters, future treatments will be expensive and on a scale well beyond all other oncology treatments to date. ACT therapies will require a very different approach to pricing and market access than anything that has come before.
The CAR-T cell therapies Kymriah and Yescarta are produced by deriving cells from the patient, reengineering them in a laboratory to recognize and kill cancer cells, and then multiplying them and infusing them back into the patient (see chart).
Investment in CAR-T drugs is strong, with more than 270 trials underway in this space. Of the approximately 40 companies developing CAR-T cell therapies, the leading players currently include Novartis, Kite Pharma (now part of Gilead Sciences), Juno Therapeutics (in association with Celgene), Bluebird Bio (also in association with Celgene), and Cellectis (in collaboration with Pfizer). According to Coherent Market Insights, the global CAR-T cell therapy market is estimated at $72 million today, with projected growth at a staggering CAGR of 46.1% between 2019 and 2028.
Payers will be facing a number of difficulties in evaluating and covering ACT therapies-challenges that biopharma companies must actively address in their commercialization strategies.
Limitations in assessing clinical benefit
At the time of launch, the evidence base for ACT therapies will likely be immature and may not support conclusions on their potential long-term benefits. Indeed, many of these treatments may be approved on the basis of Phase II trials in relatively small patient samples, without long-term, real-world follow-up. It is safe to assume that payers will be unwilling to make the leap of faith on long-term benefit without some kind of
proof or guarantee. However, they are unlikely to expect data from ~10-year-long trials. Payers also want to be able to compare the efficacy of a new product with the standard of care, although, in most cases, the data on newly launched ACT therapies will likely not be robust enough for such comparisons.
As with other immuno-oncology treatments, ACT therapies are likely to work well for a portion of patients, providing remission for a number of years. In Kymriah’s case, 83% of patients achieved complete remission or incomplete response with blood count recovery within three months of infusion. Payers (along with the entire medical community) will be eager for more insights into which subgroups of patient will benefit from the treatment.
Classification as a medical procedure
As mentioned, ACT therapy is typically developed though an individualized process for each patient, and treatment is provided in the hospital, similar to stem-cell transplants.
This means that in the US, the manufacturer’s customer is the hospital system/provider, and only a small number (perhaps 10 to 15) of centers of excellence are likely to be capable of offering the treatment. Payers must negotiate contracts with these facilities and be prepared to address policy issues around access and funding, in particular for patients who do not live near one of these centers.
In the major five European markets (France, Germany, Italy, Spain, and the UK), treatment will likely be covered by the hospital funding mechanisms, such as are in place for organ transplants. Funding is typically based on a single, fixed-price per patient to cover costs from the date of admission to a certain number of months post-transplant. There may be no existing mechanism for funding any additional, and costly, services related to ACT treatment.
Currently, a one-time treatment with Kymriah is priced at $475,000-a price that has pierced prior-cost barriers. (In contrast, a one-year course of treatment with a programmed death cell protein 1 [PD-1] targeted antibody is priced around $180,000). Initially, even at this price, Kymriah will present payers with limited budget impact, as it is indicated only for ALL that is refractory or in second or later relapse in children and young adults (up to 25 years of age). However, the impact on payers will change if/when Kymriah is approved for other more prevalent indications and certainly when other ACT therapies enter the market. Yescarta is priced lower than Kymriah, at $373,000, but it will serve a considerably larger patient population
in which the unmet need may not be as high.
While the downstream benefits of ACT therapy are likely to last for many years, the very high cost will be concentrated at the time of treatment. In the US, where patients tend to change medical insurers on average every two to three years, how can the cost be borne, and the benefits enjoyed, equitably? There may be a disincentive to cover such therapy if another entity yields the benefits.
So, how will ACT therapies fit into the existing funding structure? How will payers respond? Their approaches will be different by country and region, but we can expect that they will take a conservative approach when data packages are limited. Particularly in the Euopean Union (EU), payers can prolong their drug listing/formulary decision-making process as approvals work their way through national, regional, and then hospital-level bodies. It is not unusual for this process to take as long as two years. As an example, access decisions on the multiple myeloma drug Farydak® took around two years in both France and Italy. Ultimately, they can restrict or deny access based on the price.
Experience suggests that some payers will not cover such novel and expensive therapies based on immature evidence without a way to either share the risk or curb or delay the budget impact. They will look for manufacturers to enter into innovative agreements such as:
We know that, in general, payers have little appetite to accept uncertainty. A study performed by the UK’s National Institute for Health and Care Excellence (NICE) revealed that even when they had a five-year dataset (which is greater than most therapies have at launch), payers were concerned about low subject numbers and the use of a single-arm study. To secure access in this environment, manufacturers of ACT therapies will need to:
ACT therapies are so new that most payers have not yet updated their systems, policies, or budgets to accommodate them. Thus, it is impossible to know exactly how to meet their requirements, but manufacturers with ACT therapies in the pipeline should be actively exploring this. It seems clear that early manufacturers of ACT therapies need to consider unique strategies toward evidence generation, working to understand how ACT therapies will require different payer policies, and planning new types of agreements with payers that will afford access to patients.
Jill Condello is Vice President, Strategic Services; Andrea Favaro is Senior Consultant, Pricing and Market Access; Martin Lachs is VP, Project Management, Oncology; and Rebecca Walker is Principal, Pricing and Market Access; all with ICON plc