The Institute for Clinical and Economic Review (ICER) has published its definitive evidence report on gene therapies for Sickle Cell Disease (SCD). Despite some uncertainty regarding long-term outcomes, both lovo-cel and exa-cel are anticipated to yield significant improvements in patients' length and quality of life. An independent appraisal committee has voted in favour of the available evidence demonstrating a net health benefit compared to standard care.
Moreover, current evidence suggests that these therapies could meet common thresholds for cost-effectiveness if priced in the range of $1.35 million to $2.05 million. ICER's recommendations encourage drug manufacturers to consider pricing at the lower end of this range to enhance accessibility and affordability for all individuals covered by various insurance systems.
In clinical trials, lovo-cel achieved a remarkable resolution of 90% of participants' vaso-occlusive events (VOEs) within six to 18 months post-infusion, with 30 out of 31 patients free from severe VOEs. In a single trial of exa-cel involving 35 participants, 16 out of 17 (94.1%) with 12 months of follow-up were free of severe VOCs. Serious adverse events occurred in both trials, primarily attributed to myeloablative conditioning required before receiving these therapies. However, concerns persist regarding the long-term safety of gene therapies.
The FDA had previously placed a clinical hold on lovo-cel due to safety concerns linked to hematologic malignancies, including two fatal cases of acute myeloid leukaemia. While not directly related to gene insertion, these events are atypical for SCD patients, necessitating close monitoring as more patients receive gene therapy. Furthermore, it's still being determined if trial results apply to a broader SCD population that didn't meet trial eligibility criteria.
Assessing net health benefits, lovo-cel shows marked improvement in a small group of severe SCD patients. However, concerns arise from the potential severe harms of myeloablative conditioning and uncertainties about long-term benefits. For severe SCD patients, lovo-cel is seen as providing at least an incremental net benefit compared to standard care, potentially substantial ("Incremental or Better," B+).
Exa-cel presents similar concerns, with additional uncertainties due to its limited use in patients to date and the relative novelty of CRISPR therapy compared to lentiviral gene therapy. For severe SCD patients, exa-cel treatment may be comparable, resulting in an incremental or substantial net benefit compared to standard care ("Comparable or Better," C++).
When comparing lovo-cel to exa-cel, the evidence is "Insufficient" (I) because of their different mechanisms of action, leaving the possibility that future research may uncover differences in effectiveness or safety between the two therapies.
Budget impact: The findings indicated that with a provisional cost of $2 million per treatment course for either lovo-cel or exa-cel, to be paid upfront, approximately 15.5% of individuals (equivalent to 388 people annually) could receive treatment over five years without surpassing the ICER budget impact limit of $777 million per year.
Key Policy Recommendations:
ICER's impartial assessment of value serves as a crucial resource for stakeholders throughout the U.S. healthcare system, guiding decisions related to pricing and coverage. Following the voting session, a policy roundtable of experts, including manufacturers, clinical experts, patient advocates, and representatives from U.S. payers, gathered to discuss pricing implications and recommendations to ensure equitable access. Key recommendations arising from the roundtable discussions encompass:
Suppose the announced prices for lovo-cel and exa-cel align with the anticipated patient benefits and fall within the lower range of their estimated cost-effectiveness. In that case, payers should base coverage policies on the FDA label, avoiding restrictions unrelated to the likelihood of treatment benefits.
Manufacturers should collaborate with payers to establish meaningful alternative payment models addressing gene therapies' substantial short-term budget impact and the uncertainty surrounding long-term safety and benefits.
Manufacturers and the clinical research community should work together to develop cohort studies and real-world evidence programs that assess gene therapies' long-term safety and durability.