ICER draft report says sickle-cell disease treatments Adakveo, Oxbryta, Endari not cost-effective

The Institute for Clinical and Economic Review (ICER) has issued a preliminary report of its ongoing cost-effectiveness analysis of Novartis' Adakveo (crizanlizumab), Global Blood Therapeutics' Oxbryta (voxelotor) and Emmaus Life Sciences' Endari (L-glutamine). ICER said that while the sickle-cell disease (SCD) therapies appear to offer health benefits, questions remain about the magnitude of these benefits and overall impact on quality of life, and all three were deemed too expensive based on the group's cost-effectiveness thresholds. 

The FDA approved Adakveo, an anti-P-selectin antibody, last November to reduce the frequency of vaso-occlusive crises in adult and paediatric patients aged 16 years and older with SCD. That was followed shortly after by approval for Oxbryta, a haemoglobin polymerisation inhibitor indicated to treat SCD in adults and children 12 years and older. Meanwhile, Endari was cleared in the US in 2017 to reduce severe SCD-associated complications in patients aged five years and up. 

According to ICER, price was the main driver of the cost-effectiveness results given that many patients will discontinue each treatment. The group calculated that Adakveo's average annual cost of $88,000 should be cut to $25,410 in order to be cost-effective at the threshold of $150,000 per quality-adjusted life year (QALY). Similarly, the cost of $84,000 for Oxbryta and $24,000 for Endari should be reduced to $9218 and $3859, respectively, it said. 

The group noted that improvements in QALYs gained were "relatively small" for the three drugs, with all incremental cost-effectiveness ratios exceeding $1 million per QALY. In addition, it said none of the scenario analyses it did for the treatments lowered the estimated cost per QALY to less than $150,000 per QALY. 

ICER indicated that while reducing acute SCD-related pain crises and raising haemoglobin levels provides relief to patients, the impact of the three therapies on other acute and chronic conditions SCD patients are likely to continue to face hasn't yet been demonstrated in clinical trials. As a result, it said "there is currently a large difference in the cost per QALY and the cost per life-year and evLYGs (equal value life years gained)," the last of which is a relatively recent tool used by ICER that measures any gains in length of life, regardless of the treatment's ability to improve a patient's quality of life. "For example, cost per evLYG ranged from approximately $520,000 for Adakveo to $847,000 for Endari," the report said. 

ICER also pointed to scenario analyses suggesting treatment is most cost-effective for patients with higher rates of acute pain crises, noting that those who experience 10 acute pain crises per year may have a cost per QALY as low as $615,000 with Adakveo. 

Commenting on the draft report, Novartis said ICER did not appropriately weigh Adakveo's benefits, including reducing pain crises or also potentially helping to shorten hospital stays. "We look forward to gaining a better understanding of the approach ICER used to make its assessment and to helping them better understand the value of Adakveo," Novartis said. Meanwhile, GBT suggested that ICER's review conflicts with the FDA's goal of speeding up the availability of medicines to patients, arguing the group's analysis is "flawed, premature and risks adversely impacting access to new, potentially transformative therapies." 

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