When advisers to the US Centers for Medicare and Medicaid Services meet tomorrow in Washington, DC, to evaluate payment for CAR-T therapies, they will be asked to consider a central question: should how patients feel be used to calculate reimbursement?
The discussion will probably be wider ranging , but the main issue that CMS officials want its advisory committee to decide is what patient-reported outcomes (PROs) are relevant for Medicare-eligible lymphoma treatment with Novartis’s Kymriah and Gilead’s Yescarta. While it does not appear that PROs will be immediately incorporated into Medicare’s reimbursement rates, the US government is sending a signal that it expects eventually to base its fees on more than just whether patients go into remission.
The meeting of the Medicare Evidence Development and Coverage Advisory Committee (Medcac) was triggered by a request from United Healthcare’s Medicare Advantage division to develop a national coverage policy on Kymriah and Yescarta, the $400,000 autologous haematological cancer therapies that could soon be joined by projects from Celgene and Bluebird.
United asked CMS to develop a process to adjust coverage policies quickly based on emerging data relating both to efficacy and side effects. The latter creates significant financial risks for payers as patients are often re-admitted to hospital owing to treatment-related toxicity, which is why CMS is interested in requiring pharma companies to gather PRO data as a condition of coverage.
Notably, Novartis is resisting such a move on the grounds of difficulty. A further problem at present is that PROs such as quality of life are not routinely collected by hospitals or registries.
For now, CMS is not expected to do much beyond restricting payment to the labelled indication of the Novartis and Gilead products in third-line relapsed or refractory large B-cell lymphoma. The Medcac’s task will be to decide what PROs are relevant for these patients, and over what period (six to 24 months) a benefit would on PROs would be considered meaningfully durable.
In the case of CAR-T, remission and the possibility of extended survival need to be considered, but other important factors include the significant side effects of cytokine release syndrome and neurological toxicity, not to mention relief from symptoms such as fatigue and pain.
These factors feed into health technology assessments such as those prepared by the Institute for Clinical and Economic Review, which measure the cost effectiveness of agents like Kymriah and Yescarta based on “quality adjusted life years” (Qalys). Symptomatic relief increases the number of Qalys and, consequently, their cost-effectiveness; side effects decrease Qalys.
Patient-centred research has been growing in importance in FDA decision-making, as pharma has pushed regulators to consider not just hard scientific safety and efficacy endpoints, but also whether patients feel like their symptoms improve (Vantage point – Patient-reported data gain traction in FDA decisions, June 8, 2016).
As is frequently the case when it comes to patient access US regulators lag behind their opposite numbers in Europe, where the issue of patient-reported outcomes in CAR-T therapy has already been discussed.
In February the EMA held a workshop on CAR-T patient registries, which it said would play an essential role given the need for long-term follow-up, and hearing input from, among others, the US Center for International Blood and Marrow Transplant Research (CIBMTR).
Among the workshop’s recommendations was that all “stakeholders” should collaborate to define PROs that could feasibly be collected systematically.
Certain PROs might be of relevance for health technology assessments and reimbursement bodies, as well as for patients. The CIBMTR put forward the idea of an electronic PRO instrument that could be developed for a subset of patients, noting that collecting quality-of-life data might be impractical given that most CAR-T toxicities tended to be short-lived.
Naturally, Kymriah's developer, Novartis, is pushing back against mandating PRO data collection. In a presentation prepared for delivery at Medcac, it says this is “unnecessary, impractical and imposes a significant burden on providers and patients”.
In this view Novartis is joined by Gunjan Shah, from the Memorial Sloan Kettering Cancer Center’s health policy and outcomes branch, who says PROs are too early in development to mandate, and Heather Jim, from the Moffit Cancer Center’s health outcomes and behaviour department, who says there is not enough PRO data to make reimbursement decisions.
While some in the cell therapy space had seen the writing on the wall early, issues around reimbursement, along with low take-up and difficulty of scheduling patients to undergo complex manufacturing are only becoming evident now that Kymriah and Yescarta are available commercially.
A recent physician survey conducted by Stifel analysts confirmed some of these problems, with specialists citing hospitals’ ability to treat just one or two commercial CAR-T patients a week. The issue of peripheral treatment costs was highlighted as a “significant unknown”, and the perceived risk that treating too many patients without fully understanding the extent of peripheral costs could break the bank acts as a brake on centres’ willingness to treat more than a handful of eligible patients.
And the current six to 12-month time lag in hospital billing often means that centres do not see the entirety of costs in real time, Stifel reported, and key opinion leaders said understanding the total cost of treating a CAR-T patient currently represented a significant administrative undertaking.
This does not take anything away from the fact that CAR-T is one of the most noteworthy advances in cancer treatment in recent years, but payers and policymakers now are wrestling with how to deliver this therapy in the real world.
CAR-T is one of the most noteworthy advances in cancer treatment in recent years, but
payers and policymakers now are wrestling with how to deliver this therapy in the real world.