ICER Releases Final Evidence Report on Beti-Cel to Treat Beta Thalassemia

The Institute for Clinical and Economic Review (ICER) released the report, which supports the long-term value of betibeglogene autotemcel (beti-cel) for the treatment of beta thalassemia.

The Institute for Clinical and Economic Review (ICER) has released a final evidence report supporting the long-term value of betibeglogene autotemcel (beti-cel) for the treatment of beta thalassemia.

Beti-cel is a gene therapy manufactured ex vivo, modifying a patient’s hematopoietic stem cells (HSCs) by adding functional copies of the β-globin gene before intravenous infusion back into the patient. The FDA accepted a biologics license application from manufacturer bluebird bio for priority review on November 22, 2021, and the PDUFA date is currently set for August 19, 2022.

Beti-cel’s pricing is expected to be an outcome-based payment plan of 5 yearly payments, for a total of $2.1 million for those who achieve transfusion independence and remain independent.

The ICER report focused on the clinical benefits of beti-cel and its cost-effectiveness vs standard clinical management for beta thalassemia. Management of the most severe form, transfusion-dependent thalassemia (TDT), entails lifelong blood transfusions and iron chelation therapy to avoid iron overload.

Allogenic hematopoietic stem cell transplantation (HSCT) from a matched donor was previously the only curative option, but the conditioning chemotherapy that HSCT requires puts patients at a higher risk of complications, such as graft-vs-host disease, post transplant.

“Patients and clinicians reported to us that living with severe forms of beta thalassemia requires being ‘tethered to the health care system’ and often to a specific region near a medical center that can provide thalassemia care,” the report said. “Some patients receive transfusions as often as every 2 weeks, and nearly all patients plan their lives around transfusions.”

ICER’s systematic review included 5 studies of beti-cel: 2 phase 1/2 trials, 2 phase 3 trials, and 1 long-term follow-up cohort study of trial participants. More emphasis was placed on the phase 3 trials, as manufacturing changed between the phase 1/2 and 3 trials. All 4 of the trials were single-arm, open-label studies.

In the phase 3 trials, 90% of patients achieved transfusion independence and sustained that for a median of 42 months. Notably, the authors do not consider this duration long enough to confirm beti-cel’s durability over a longer time period.Overall, the report deems beti-cel superior to the current standard of care, but with uncertain long-term net health benefits.

Where cost-effectiveness is concerned, the report cites public suggestions by the manufacturer indicating that beti-cel will be priced based on clinical value to patients, not its ability to offset the cost of the current standard-of-care therapies.

“ICER’s single and short-term therapy (SST) value assessment framework includes a scenario analysis where half the cost offsets from an SST are returned to society rather than all being credited to the price of the treatment,” the authors wrote. “While in the base case, no discount is needed from the anticipated price of $2.1 million to achieve typical ICER Health Benefit Price Benchmarks (HBPBs), assuming 50/50 shared savings, the HBPB range is $1.3 to $1.8 million.”

Overall, the ICER analysis determined that considering the $2.1 million price point and 80% payback option if patients do not achieve transfusion independence, all eligible patients could undergo treatment with beti-cel over 5 years without exceeding the ICER budget impact threshold of $734 million per year.

All of the 12 panelists who voted at the public meeting agreed that the evidence supports the use of beti-cel vs the current standard management of beta thalassemia, and 9 of the panelists voted that beti-cel carries a high long-term value for its cost despite uncertainty about durability.

The report recommends that payers and policymakers consider the lifetime impact on quality of life that beti-cel may have vs regular lifelong transfusions, which could positively impact both patients and caregivers. From the payer perspective, ICER recommends using the FDA label as a guide for coverage, not narrowing patient eligibility based on clinical trial populations. Manufacturers should price treatment based on independent estimates of the therapeutic value to patients, the report suggests.

Overall, stakeholders should facilitate access to curative beta thalassemia therapies in general to avoid exacerbation of disparities, the report concludes.

“Beta thalassemia is a serious blood disorder, and while treatment has improved, patients with TDT still have decreased life expectancy and burdensome care that impacts all aspects of their lives,” said David Rind, MD, chief medical officer at ICER, in a statement. “Previously, a minority of patients had access to curative allogeneic bone marrow transplant; beti-cel provides an additional potentially curative option for many patients with TDT. New potentially curative therapies for beta thalassemia bring the promise of considerable lifetime benefit, but there also remains substantial uncertainty regarding longer-term safety and the durability of benefits. Beti-cel is cost-effective at a high price in part because it offsets current very high costs of care; a somewhat lower price would be needed if half of those offsets were returned to the medical system.”


Betigeblogene autotemcel for beta thalassemia: effectiveness and value. ICER. July 19, 2022. Accessed July 22, 2022.

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