Despite safety concerns, gene therapies clinically beneficial for sickle cell disease
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Key takeaways:
- Gene therapies substantially improve quality and length of life among patients with sickle cell disease.
- Two one-time gene therapies would be cost-effective if priced between $1.35 million and $2.05 million.
Evidence suggests two investigational gene therapies provide net health benefits compared with standard approaches for sickle cell disease, according to a revised evidence report from Institute for Clinical and Economic Review.
The report — along with a subsequent Institute for Clinical and Economic Review (ICER) regional California Technology Assessment Forum (CTAF) panel — expressed less confidence about the long-term safety and efficacy of lovotibeglogene autotemcel (lovo-cel; bluebird bio) and exagamglogene autotemcel (exa-cel; CRISPR Therapeutics, Vertex Pharmaceuticals).
Lovotibeglogene autotemcel — often called lovo-cel — uses a lentivirus vector to insert a functioning version of the HBB gene into the patient’s own stem cells. Exagamglogene autotemcel — often called exa-cel — deploys CRISPR-based technology to delete a portion of the BC11A gene to increase the amount of fetal hemoglobin in red blood cells.
“Although uncertainties about durability and harm remain, both lovo-cel and exa-cel are likely to substantially improve quality and length of life among patients with [sickle cell disease],” the report read. “Serious adverse events were attributed to myeloablative conditioning, they were not infrequent, and chemotherapy is required before receiving both lovo-cel and exa-cel.”
The FDA accepted biologics license applications for both one-time gene therapies. Regulatory decisions about commercial availability are expected in December.
The report concluded that lov-cel provided at least an “incremental net benefit” compared with standard therapies, equating to a “incremental or better” B+ rating over standard therapies for individuals with sickle cell disease.
Exa-cel earned a C++ rating of “comparable or better,” meaning the benefit it provides may range from comparable to “substantial net health benefit” compared with standard sickle cell disease therapies.
Data from the report showed that lovo-cel and exa-cel would achieve common thresholds for cost-effectiveness if priced between $1.35 million to $2.05 million per treatment.
The CTAF panel cast separate 13-1 votes declaring the net health benefits of exa-cel and lovo-cel superior to standard treatments, such as hydroxyurea, chronic blood transfusions, pain medication or iron chelation.
The panel unanimously concluded that current available evidence — including lack of head-to-head comparative trials or indirect comparative analyses — could not allow them to determine if either gene therapy would provide a net health benefit.
CTAF panelists expressed concerns about the long-term safety and efficacy of exa-cel, the first CRISPR-based gene therapy to apply for FDA approval. The ICER report raised the issue of short follow-up contributing to uncertainty about safety.
“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 sickle cell to achieve a cure,” David Rind, MD, ICER’s chief medical officer, said in a press release.
“These first two genetic therapies, using different technologies and altering different genetic targets, may mean that day has nearly arrived,” Rind added. “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.”
References:
- Beaudoin F, et al. Gene therapies for sickle cell disease: evidence report. Institute for Clinical and Economic Review, July 13, 2023. Available at: https://icer.org/assessment/sickle-cell-disease-2023/. Accessed July 31, 2023.
- Institute for Clinical and Economic Review. ICER publishes evidence report on gene therapies for sickle cell disease (press release). July 13, 2023. Available at: https://icer.org/news-insights/press-releases/icer-publishes-evidence-report-on-gene-therapies-for-sickle-cell-disease/. Accessed July 31, 2023.
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