Report: Cost of CAR T-cell therapies aligns with clinical benefit

Chimeric antigen receptor T-cell therapy improved response rates and survival for patients with cancer who have exhausted most other options, and the pricing of the therapies is aligned with their clinical value, according to a final evidence report issued by Institute for Clinical and Economic Review.

At a public meeting of the California Technology Assessment Forum, a majority of the panel voted that evidence is sufficient to show that the evaluated chimeric antigen receptor (CAR) T-cell therapies have a net health benefit for their specific indications.

Tisagenlecleucel (Kymriah, Novartis) is indicated for the treatment of patients aged younger than 25 years with relapsed/refractory B-cell acute lymphoblastic leukemia. The FDA is assessing tisagenlecleucel for the treatment of patients with relapsed/refractory non-Hodgkin lymphoma and, therefore, ICER included this indication in the report.

Axicabtagene ciloleucel (Yescarta, Kite Pharma/Gilead) is indicated for the treatment of adults with relapsed/refractory B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma, transformed follicular lymphoma and primary mediastinal B-cell lymphoma.

The Institute for Clinical and Economic Review (ICER) report included information from available clinical trial data and long-term cost-effectiveness estimates. The draft report had been open to public comment and underwent a panel discussion last month.

 

Net health benefit

The final report concluded available evidence supported a “moderate certainty of a small or substantial net health benefit” for each therapy for its indications compared with chemotherapy.

The available evidence for CAR T-cell therapies showed improved complete remission, DFS and OS across indications, with the exception of DFS among patients with non-Hodgkin lymphoma treated with tisagenlecleucel, for which there was no available evidence.

Significant limitations to the clinicals studies of CAR T-cell therapy included that all are single-arm design and have small samples sizes and short follow-up. Additionally, some are unpublished or missing data.

Despite these limitations, the contributors of the report concluded there is at least some net health benefit, although more and longer-term data are needed.

Additionally, there are no head-to-head trials of tisagenlecleucel and axicabtagene ciloleucel for patients with relapsed/refractory B-cell lymphomas, so neither therapy could be determined as superior.

CAR T-cell therapy has been associated with potentially harmful risks, including cytokine release syndrome, neurotoxicity and B-cell aplasia. However, these risks are manageable, and clinicians perceive them as no worse than the serious adverse events associated with chemotherapy.

Due to uncertainty surrounding the long-term risks and benefits, the panel voted that tisagenlecleucel provides an intermediate long-term value. The panel’s votes were split between low long-term value and intermediate long-term value for axicabtagene ciloleucel.

“Given the currently available evidence, these therapies appear to be effective options for those with B-ALL or non-Hodgkin lymphoma, although uncertainty in the evidence raised questions around the long-term value for money,” Dan A. Ollendorf, PhD, chief scientific officer of ICER, said in a press release.

 

Cost-effectiveness

ICER used a two-part model — consisting of a short-term decision tree and long-term survival model — to assess long-term cost-effectiveness of the CAR T-cell therapies.

Tisagenlecleucel is priced at $475,000 and axicabtagene ciloleucel at $373,000 for their approved indications, in addition to costs of other services associated with their administration.

Tisagenlecleucel’s manufacturer has announced an outcomes-based pricing arrangement; therefore, the analysis assumed the company would only receive payment if the patients responded to treatment at 1 month. The report also assumed survival benefits observed over the short duration of clinical trials would persist over a patient’s lifetime.

The cost-effectiveness of both therapies fell within the commonly cited thresholds of $50,000 to $150,000 per quality-adjusted life year (QALY). Tisagenlecleucel had a long-term cost effectiveness of $45,871 per QALY compared with clofarabine. Axicabtagene ciloleucel had a long-term cost effectiveness of $136,078 per QALY compared with salvage chemotherapy.

Tisagenlecleucel could remain within these thresholds even with the application of price markups from hospital-administered dugs and pricing premiums, which can be from 102% to 194%.

Axicabtagene ciloleucel also could increase in price by 11% and remain within the $150,000 per QALY threshold, but not within the more stringent $100,000 per QALY threshold.

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 receive the therapy without crossing the threshold. The analysis did not project tisagenlecleucel would cross this threshold because of the relatively small number of patients who fall within its approved indications.

As part of the final report, ICER issued an affordability and access alert for axicabtagene ciloleucel for the treatment of adults with non-Hodgkin lymphoma. This alert is intended to signal when the added costs associated with a new treatment could be difficult for the health care system to absorb over the short-term.

“Based on current evidence, both therapies appear to be priced in alignment with their clinical value, but there are potential short-term affordability concerns — for axicabtagene ciloleucel under its current indication, and for both treatments should they receive future approvals for broader patient populations,” Ollendorf said in the release.

 

Policy recommendations

The final report also included policy recommendations developed by physicians, patient advocates, manufacturer representatives and payer representatives. Those recommendations included:

Manufacturers, insurers and providers should meet prior to FDA approval to discuss a novel therapy’s role in treatment and pricing/payment parameters to avoid unnecessary delays in delivery of care to patients;

When launching novel therapeutics that are approved with limited clinical evidence, manufacturers and payers should consider either a lower or higher launch price with the potential for adjustment based on real clinical outcomes;

Size of the eligible population should influence affordability of a new treatment in a value-based pricing system; and

All patients treated with CAR T-cell therapy should enter into a registry with planned long-term follow-up.

The panel also noted that CAR T-cell therapy should be delivered in accredited centers of excellence, so serious adverse events can be managed effectively. Patient education should also play an important role, according to the panel.

“With many other potentially transformative therapies in the pipeline, stakeholders must collaborate now to develop payment and delivery systems that can ensure timely patient access, manage short-term affordability for expensive one-time treatments, and continue to reward the innovation that brings these new treatments to market,” Ollendorf said. – by Cassie Homer

 

Disclosures: Ollendorf reports employment with ICER. Please see the full report for all authors’ relevant financial disclosures.

Chimeric antigen receptor T-cell therapy improved response rates and survival for patients with cancer who have exhausted most other options, and the pricing of the therapies is aligned with their clinical value, according to a final evidence report issued by Institute for Clinical and Economic Review.

At a public meeting of the California Technology Assessment Forum, a majority of the panel voted that evidence is sufficient to show that the evaluated chimeric antigen receptor (CAR) T-cell therapies have a net health benefit for their specific indications.

Tisagenlecleucel (Kymriah, Novartis) is indicated for the treatment of patients aged younger than 25 years with relapsed/refractory B-cell acute lymphoblastic leukemia. The FDA is assessing tisagenlecleucel for the treatment of patients with relapsed/refractory non-Hodgkin lymphoma and, therefore, ICER included this indication in the report.

Axicabtagene ciloleucel (Yescarta, Kite Pharma/Gilead) is indicated for the treatment of adults with relapsed/refractory B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma, transformed follicular lymphoma and primary mediastinal B-cell lymphoma.

The Institute for Clinical and Economic Review (ICER) report included information from available clinical trial data and long-term cost-effectiveness estimates. The draft report had been open to public comment and underwent a panel discussion last month.

 

Net health benefit

The final report concluded available evidence supported a “moderate certainty of a small or substantial net health benefit” for each therapy for its indications compared with chemotherapy.

The available evidence for CAR T-cell therapies showed improved complete remission, DFS and OS across indications, with the exception of DFS among patients with non-Hodgkin lymphoma treated with tisagenlecleucel, for which there was no available evidence.

Significant limitations to the clinicals studies of CAR T-cell therapy included that all are single-arm design and have small samples sizes and short follow-up. Additionally, some are unpublished or missing data.

Despite these limitations, the contributors of the report concluded there is at least some net health benefit, although more and longer-term data are needed.

Additionally, there are no head-to-head trials of tisagenlecleucel and axicabtagene ciloleucel for patients with relapsed/refractory B-cell lymphomas, so neither therapy could be determined as superior.

CAR T-cell therapy has been associated with potentially harmful risks, including cytokine release syndrome, neurotoxicity and B-cell aplasia. However, these risks are manageable, and clinicians perceive them as no worse than the serious adverse events associated with chemotherapy.

Due to uncertainty surrounding the long-term risks and benefits, the panel voted that tisagenlecleucel provides an intermediate long-term value. The panel’s votes were split between low long-term value and intermediate long-term value for axicabtagene ciloleucel.

“Given the currently available evidence, these therapies appear to be effective options for those with B-ALL or non-Hodgkin lymphoma, although uncertainty in the evidence raised questions around the long-term value for money,” Dan A. Ollendorf, PhD, chief scientific officer of ICER, said in a press release.

 

Cost-effectiveness

ICER used a two-part model — consisting of a short-term decision tree and long-term survival model — to assess long-term cost-effectiveness of the CAR T-cell therapies.

Tisagenlecleucel is priced at $475,000 and axicabtagene ciloleucel at $373,000 for their approved indications, in addition to costs of other services associated with their administration.

Tisagenlecleucel’s manufacturer has announced an outcomes-based pricing arrangement; therefore, the analysis assumed the company would only receive payment if the patients responded to treatment at 1 month. The report also assumed survival benefits observed over the short duration of clinical trials would persist over a patient’s lifetime.

The cost-effectiveness of both therapies fell within the commonly cited thresholds of $50,000 to $150,000 per quality-adjusted life year (QALY). Tisagenlecleucel had a long-term cost effectiveness of $45,871 per QALY compared with clofarabine. Axicabtagene ciloleucel had a long-term cost effectiveness of $136,078 per QALY compared with salvage chemotherapy.

Tisagenlecleucel could remain within these thresholds even with the application of price markups from hospital-administered dugs and pricing premiums, which can be from 102% to 194%.

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Axicabtagene ciloleucel also could increase in price by 11% and remain within the $150,000 per QALY threshold, but not within the more stringent $100,000 per QALY threshold.

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 receive the therapy without crossing the threshold. The analysis did not project tisagenlecleucel would cross this threshold because of the relatively small number of patients who fall within its approved indications.

As part of the final report, ICER issued an affordability and access alert for axicabtagene ciloleucel for the treatment of adults with non-Hodgkin lymphoma. This alert is intended to signal when the added costs associated with a new treatment could be difficult for the health care system to absorb over the short-term.

“Based on current evidence, both therapies appear to be priced in alignment with their clinical value, but there are potential short-term affordability concerns — for axicabtagene ciloleucel under its current indication, and for both treatments should they receive future approvals for broader patient populations,” Ollendorf said in the release.

 

Policy recommendations

The final report also included policy recommendations developed by physicians, patient advocates, manufacturer representatives and payer representatives. Those recommendations included:

Manufacturers, insurers and providers should meet prior to FDA approval to discuss a novel therapy’s role in treatment and pricing/payment parameters to avoid unnecessary delays in delivery of care to patients;

When launching novel therapeutics that are approved with limited clinical evidence, manufacturers and payers should consider either a lower or higher launch price with the potential for adjustment based on real clinical outcomes;

Size of the eligible population should influence affordability of a new treatment in a value-based pricing system; and

All patients treated with CAR T-cell therapy should enter into a registry with planned long-term follow-up.

The panel also noted that CAR T-cell therapy should be delivered in accredited centers of excellence, so serious adverse events can be managed effectively. Patient education should also play an important role, according to the panel.

“With many other potentially transformative therapies in the pipeline, stakeholders must collaborate now to develop payment and delivery systems that can ensure timely patient access, manage short-term affordability for expensive one-time treatments, and continue to reward the innovation that brings these new treatments to market,” Ollendorf said. – by Cassie Homer

 

Disclosures: Ollendorf reports employment with ICER. Please see the full report for all authors’ relevant financial disclosures.

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