ICER Rates Exa-Cel and Lovo-Cel Cost-Effective up to $2 Million


The updated report maintains exa-cel's C++ grade and lovo-cel's B+ grade.

The Institute for Clinical and Economic Review (ICER) has posted a finalized version of its evidence report assessing the cost effectiveness of gene therapy for sickle cell disease (SCD), namely exagamglogene autotemcel (exa-cel; Vertex Pharmaceuticals and CRISPR Therapeutics) and lovotibeglogene autotemcel (lovo-cel, bluebird bio).1

“Sickle cell disease can affect nearly every organ system in the body, and severe sickle cell disease affects nearly every aspect of a person’s life,” David Rind, MD, chief medical officer, ICER, said in a statement.2 “From the earliest days of gene therapy, patients, families, and clinicians have imagined that someday it might be possible to address the underlying genetics of SCD to achieve a cure. These first 2 genetic therapies, using different technologies and altering different genetic targets may mean that day has nearly arrived. However, the need for autologous bone marrow transplantation with these therapies means they come with important potential risks, and the first CRISPR therapy necessarily has even greater uncertainties about longer-term risks and durability of benefit than a lentiviral gene therapy.”

The report, an updated version of a May 2023 draft, includes revisions made based on comments from patient groups, clinicians, drug manufacturers, and other stakeholders and will be reviewed at a virtual public meeting of the California Technology Assessment Forum on July 27, 2023.3 While much of the report remains the same, ICER did update the calculated health-benefit price benchmark for lovo-cel and exa-cel to be between $1.35M to $2.05M. The report includes collaborative input from patients, clinicians, and caregivers about quality of life, safety, access, and outcomes with standard-of-care (SOC) and gene therapy for SCD, as well as from health economists, payers, and manufacturers to compare cost-effectiveness. SOC consists of supportive care, hydroxyurea, and blood transfusions in some patients.

The report reviewed efficacy, safety, and patient-important outcomes in participants treated with lovo-cel in the HGB-205 (NCT02151526) or HGB-206 (NCT02140554) studies or exa-cel in the CLIMB-121 study (NCT03745287). Exa-cel is a CRISPR-edited gene therapy and could be the first of its kind to be FDA-approved. The FDA accepted the biologics license application (BLA) for exa-cel for the indications of SCD and transfusion-dependent β-thalassemia (TDT) in June 2023 and bluebird bio submitted the BLA for lovo-cel for SCD in April 2023.4,5 The updated report maintains exa-cel's C++ grade and lovo-cel's B+ grade, with points docked for the remaining uncertainty of long-term safety effects of gene therapy and CRISPR therapy especially.1

READ MORE: 2023 World Sickle Cell Day: The Home Stretch for Gene Therapy in SCD?

The most recent data on exa-cel were presented at the European Hematology Association (EHA) 2023 Congress. The data showed that out of 17 patients evaluable patients, 16 (94.1%) achieved the primary endpoint of freedom from vaso-occlusive crises (VOCs) for at least 12 consecutive months (95% CI [71.3-99.9]; P = .0001).6 Patients had a mean duration of 18.7 months VOC-free, ranging up to 36.5 months. All patients achieved the key secondary endpoint of being free from hospitalizations related to VOCs for at least 12 consecutive months (95% CI: 80.5%, 100.0%; P <.0001). Fetal hemoglobin of around 30-40% was maintained throughout the study and patients also had clinically significant improvements in patient-reported outcomes.

The most recent data from the ongoing HGB-206 trial showed that 96% of patients treated in Group C experienced complete resolution of severe VOCs through 24 months of follow-up.7 Serious AEs related tolovo-cel included a case of grade 2 febrile neutropenia and 2 cases of development of persistent, non-transfusion-dependent anemia in pediatric patients; the latter AE prompted a clinical hold by the FDA in late 2021. Other deaths previously occurred that were not related to the gene therapy but possibly related to myeloablative conditioning.

“It is indeed a very exciting time for the field of sickle cell disease. We are looking forward to not just 1 but 2 potential gene therapy approvals this year. These autologous therapies are surely going to remove a lot of barriers and allow many more patients to pursue them,” Akshay Sharma, MBBS, assistant member, bone marrow transplant department, St. Jude Children’s Research Hospital, told CGTLive in an interview.

1. ICER. Gene Therapies for Sickle Cell Disease Evidence Report. July 13, 2023. Accessed July 14, 2023.
2. ICER publishes evidence report on gene therapies for sickle cell disease. News release. ICER. July 13, 2023. Accessed July 14, 2023.
3. Gene therapies for sickle cell disease. Draft Evidence Report. ICER. April 12, 2023. Accessed July 14,2023.
4. FDA accepts Biologics License Applications for exagamglogeneautotemcel (exa-cel) for severe sickle cell disease and transfusion-dependent Beta thalassemia. News release. Vertex Pharmaceuticals. June 8, 2023. Accessed June 19, 2023.
5. bluebird bio Submits Biologics License Application (BLA) to FDA for lovotibeglogeneautotemcel (lovo-cel) for Patients with Sickle Cell Disease (SCD) 12 years and Older with a History of Vaso-Occlusive Events. News release. bluebird bio, Inc. April 24, 2023. Accessed June 19, 2023.
6. Positive Results From Pivotal Trials of exa-cel for Transfusion-Dependent Beta Thalassemia and Severe Sickle Cell Disease Presented at the 2023 Annual European Hematology Association (EHA) Congress. News release. Vertex Pharmaceuticals. June 9, 2023. Accessed June 19, 2023.
7. Walters MC, Thompson AA, Kwiatkowski JL, et al. Lovo-cel (bb1111) Gene Therapy for Sickle Cell Disease: Updated Clinical Results and Investigations into Two Cases of Anemia from Group C of the Phase 1/2 HGB-206 Study. Presented at: ASH 2022 Annual Meeting. December 10-12, 2022; New Orleans, LA. Abstract 11.
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