RARE Daily

ICER Finds SCD Gene Therapies Could Be Cost Effective at $2 Million

April 13, 2023

Rare Daily Staff

The Institute for Clinical and Economic Review, an independent non-profit research institute that analyzes the value of therapies, released a draft evidence report that found gene therapies for sickle cell disease from Vertex Pharmaceuticals and CRISPR Therapeutics and from Bluebird Bio could be cost effective at around $2 million each.

ICER said that while uncertainties about durability and harm remain, both Vertex and CRISPR’s exa-cel and Bluebird’s lovo-cel are likely to substantially improve quality and length of life. “Ultimately,” ICER wrote, “cost effectiveness will depend on the actual prices for these therapies.” ICER said the companies are expected to seek approval for these therapies in the first half of 2023.

Sickle cell disease (SCD) is a serious, progressive and debilitating genetic disease caused by a mutation in the β-globin gene that leads to the production of abnormal sickle hemoglobin, causing red blood cells to become sickled and fragile, resulting in chronic hemolytic anemia, vasculopathy and painful vaso-occlusive events. For adults and children living with SCD, this means unpredictable episodes of excruciating pain due to vaso-occlusion as well as other acute complications—such as acute chest syndrome, stroke, and infections, which can contribute to early mortality in these patients.

Exa‑cel is an autologous, ex vivo CRISPR/Cas9 experimental gene‑edited therapy for patients with SCD characterized by recurrent vaso-occlusions, in which a patient’s own hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF) in red blood cells. HbF is the form of the oxygen‑carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. The elevation of HbF by exa‑cel has the potential to reduce painful and debilitating sickle crises for patients with SCD.

In the most severe forms of SCD, standard of care usually involves hydroxyurea, as-needed blood transfusions, and supportive care for acute pain crises and other acute and chronic complications.  Hematopoietic stem cell transplantation (HSCT) is currently the only potentially curative treatment for SCD, but HSCT has a risk of graft failure/rejection, graft-versus-host disease (GVHD), acute complications during the transplant process, and carries at least 4% risk of mortality even with a perfectly matched sibling donor that carries less risk of GVHD and graft failure.  There is a lack of compatible donors (especially donors that are related to the patient) and thus most people with SCD are not able to pursue HSCT as a therapeutic option even if there is interest.

“When assuming a placeholder price for lovo-cel and exa-cel of $2 million dollars and applying standard 3 percent per year discounting, these gene therapies have an incremental cost effectiveness that is above commonly cited thresholds from the health care system perspective,” ICER wrote.

The draft cost-effectiveness findings were driven by the lifetime opportunity to improve health and reduce vaso-occlusive-related and other SCD-related costs, and to improve productivity and reduce caregiver costs in the modified societal perspective.

ICER compared the therapies with each other and with standard of care consisting of supportive care, hydroxyurea, and blood transfusions in some patients.  In trials of both therapies, the main outcome was the number of vaso-occlusive events or crises (VOEs or VOCs) over two years of follow-up.

In the pivotal lovo-cel trial, 90 percent of participants achieved complete resolution of all VOEs between six and 18 months after lovo-cel infusion and 30 of 31 patients were free of severe VOEs.

In a single trial of exa-cel in 31 participants, only seven participants had 12 months of follow-up available for review, and all seven were free of severe VOCs during that time.

In both trials of both lovo-cel and exa-cel, serious adverse events were observed in the trials. Although serious adverse events were attributed to myeloablative conditioning, they were not infrequent, and chemotherapy is required before receiving both lovo-cel and exa-cel.  However, uncertainty still remains about the degree of risk of gene therapies in the real world, particularly over the long-term.

In considering net health benefit, ICER said the marked improvement seen with lovo-cel in a small number of patients with severe SCD needs to be balanced with the potentially severe harms of myeloablative conditioning in SCD and uncertainties about duration of benefit.  For people with severe SCD, it found that lovo-cel provides at least an incremental net benefit compared with standard of care and may provide a substantial net health benefit.  It rated it as “Incremental or Better” (B+).

It said exa-cel carries similar concerns with additional uncertainties given the small number of patients treated to date and that CRISPR therapy is even newer than lentiviral gene therapy. For people with severe SCD, it found that compared with standard of care, treatment with exa-cel may be comparable, result in incremental net benefit, or result in substantial net benefit. It rated this comparison as “Comparable or Better” (C++).

It said there was not sufficient evidence to compare lovo-cel with exa-cel at this time.

ICER is accepting public comments on its evidence report through May 9 and will hold a public meeting on sickle cell disease July 27.

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