— Report will be subject to public deliberation during CTAF meeting on March 2, 2018 —

BOSTON, February 15, 2018 – The Institute for Clinical and Economic Review (ICER) today released an Evidence Report assessing the comparative clinical effectiveness and value of tisagenlecleucel (KymriahTM, Novartis) and axicabtagene ciloleucel (YescartaTM, Kite Pharma/Gilead). The report found that both therapies provided improvements in response rates and survival for patients who have exhausted most other treatment options, and that the drugs are priced in alignment with their clinical value.

Both tisagenlecleucel and axicabtagene ciloleucel were evaluated for use in adults with relapsed or refractory B-cell lymphoma. Axicabtagene ciloleucel received approval for this indication in late 2017, while tisagenlecleucel is currently under FDA evaluation. Tisangenlecleucel was also evaluated for pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), for which it received FDA approval in August 2017.

This Evidence Report will be the subject of an upcoming public meeting of the California Technology Assessment Forum (CTAF) on March 2, 2018 in Oakland, CA. CTAF is one of ICER’s three independent evidence appraisal committees comprising medical evidence experts, practicing clinicians, methodologists, and leaders in patient engagement and advocacy.

“CAR-T therapies represent a critical advancement in treating B-cell malignancies,” noted Dan Ollendorf, PhD, ICER’s Chief Scientific Officer. “Based on the evidence currently available, these therapies provide important clinical benefits and appear to be priced in alignment with these benefits. However, the evidence is limited and very short-term, and we may still face short-term affordability questions that will require innovative solutions. During the public meeting, we aim to discuss possible policy solutions to ensure appropriate patient access, monitor for updated information on clinical benefit and safety, and maintain overall affordability for the health care system.”

A draft version of this report was open for a four-week public comment period. The updated Evidence Report reflects changes made based on comments received from patient groups, clinicians, the manufacturers of the therapies, and other stakeholders. Detailed responses to public comments can be found here.

Key Report Findings

Evidence on each drug for its respective indication provided moderate certainty of a small to substantial net health benefit compared to commonly-used chemotherapies. Both CAR-Ts appear to offer important clinical improvements for patients for whom other therapies have been unsuccessful; however, the treatments come with significant risks, and substantial uncertainty around their effectiveness remains, as existing trials are small, uncontrolled, and have relatively short follow-up. Current evidence is insufficient to judge whether one CAR-T therapy is superior to the other in treating lymphoma.

Economic analyses assessed the cost-effectiveness, compared to chemotherapy, of tisagenlecleucel used for pediatric patients with B-cell ALL, as well as the cost-effectiveness of axicabtagene ciloleucel for adult patients with B-cell lymphoma. For these indications, the drugs are priced at $475,000 and $373,000, respectively, in addition to costs of other services associated with administration of CAR-T therapies. It was assumed that the drug manufacturer would receive payment for tisagenlecleucel only if patients had responded to treatment at one month, based on the company’s announced outcomes-based pricing arrangement, and that the survival benefits demonstrated over the short duration of clinical trials would persist over a patient’s lifetime. The cost-effectiveness of each therapy fell below or within commonly cited thresholds of $50,000-$150,000 per quality-adjusted life year (QALY). Additional analyses suggested that cost-effectiveness findings would be less favorable if the possibility of late relapses (after available follow-up in the trials) was included.

Even after accounting for price mark-ups typical of hospital-administered drugs, tisagenlecleucel’s price could remain in alignment with value even if pricing premiums were applied. Axicabtagene ciloleucel’s price could be increased and remain in alignment with the upper threshold ($150,000 per QALY gained) but would need to be discounted to align with the lower boundary ($100,000 per QALY gained).

While cost-effective in the long-term, potential budget impact analyses found that the short-term costs of axicabtagene ciloleucel would exceed ICER’s $915 million threshold for annual budget impact at its current price; only 38% of candidate patients could be treated without crossing the threshold. This might signal a need for further consideration to balance access and affordability. Tisagenlecleucel was not projected to cross the threshold because the number of patients with relapsed B-cell leukemia in any given year is relatively small.

ICER’s review also considered additional benefits of the medications not included in clinical studies or measurable in economic evaluations. Most notably, CAR-T therapies offer a novel mechanism of action that appears to provide excellent response rates for patients in whom standard first- and second-line therapies have not been successful.

The Evidence Report, accompanying voting questions, all public comments received on the draft report, and ICER’s written response to comments, are available on the ICER website.

During the March public meeting, pre-registered stakeholders will provide brief oral comments on the report and its findings, the CTAF Panel will vote on key questions raised in the report, and a roundtable of experts will discuss recommendations for applying the evidence to policy and practice. Requests to make an oral comment were accepted during the public comment period on the Draft Evidence Report and are now closed.

Registration for the in-person meeting is open here. Registration for a live webcast of the meeting is open here.

About ICER

The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER’s reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.

ICER’s reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER’s reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER’s website.