Trifecta of sickle cell disease therapies extend life expectancy, but are not cost-effective — ICER
Different therapeutic traits brandished by the three approved therapies for sickle cell disease all extend life expectancy, but their impact on quality of life is uncertain and their long-term cost-effectiveness is not up to scratch according to the thresholds considered reasonable by ICER, the non-profit concluded in a draft guidance report on Thursday.
Sickle cell disease (SCD), which encompasses a group of inherited red blood cell disorders that typically afflict those of African ancestry, impacts hemoglobin — and is characterized by episodes of searing pain as well as organ damage.
In recent years — three therapies have won FDA approval. The first — approved in 2017 to reduce the severe complications that come with SCD — is Emmaus’ Endari, which is a purified (pharmaceutical grade) version of the amino acid L-glutamine.
Late last year two other therapies received FDA approvals in quick succession. Novartis’ crizanlizumab, branded Adakveo, was given the FDA nod for its ability to prevent vaso-occlusive crises (VOCs) —periodic episodes of debilitating pain that occur when sickle-shaped red blood cells get stuck inside blood vessels and deprive the body of oxygen-rich blood. Soon after, Global Blood Therapeutics’ voxelotor, christened Oxbryta, was approved on the basis of data that showed it increased hemoglobin levels, although its use was not associated with fewer pain crises.
Although a decline in acute pain crises and an increase in hemoglobin will help SCD patients, there are other acute and chronic conditions that are currently not addressed with these therapies that have a significant impact on quality of life, researchers wrote in the draft report.
One of the ways ICER — an increasingly influential, privately-held, cost-effectiveness watchdog in the United States — makes its long-term cost-effectiveness calculations is using quality-adjusted-life-years or QALYs.
QALYs measure the state of health of a person or group in which the benefits — in terms of length of life — are adjusted to reflect the quality of life. Recently, ICER also incorporated the use of Equal Value of Life Years Gained (evLYG) in its calculations. The tool is designed to evenly measures any gains in length of life, regardless of the treatment’s ability to improve quality of life.
Although ICER made several assumptions over the impact of these SCD treatments on acute or chronic complications associated with the disease, there remains a large difference in the cost per QALY and evLYG, ICER said.
“For example, cost per evLYG ranged from approximately $520,000 for crizanlizumab to $847,000 for L-glutamine. Scenario analyses suggest treatment is most cost-effective for patients with higher rates of acute pain crises. Patients who experience 10 acute pain crises per year may have a cost per QALY as low as $615,000 with crizanlizumab.”
The list prices for the three treatments were the main driver of the cost-effectiveness results, with average annual costs of $88,000 for crizanlizumab, $84,000 for voxelotor and $24,000 for L-glutamine, ICER noted.
Combined with relatively small improvements in QALYs gained — 0.85 for crizanlizumab, 0.96 for voxelotor, and 0.10 for L-glutamine — all incremental cost-effectiveness ratios were estimated to be over $1 million per QALY, ICER calculated, highlighting that none of the analyses undertaken lowered the estimated cost per QALY to less than the benchmark price of $150,000 per QALY.
“We believe that ICER’s review is flawed, premature and risks adversely impacting access to new, potentially transformative therapies for SCD,” a spokesperson for Global Blood Therapeutics told Endpoints News. “The review runs counter to the FDA’s intent to provide earlier access to safe and effective treatments of serious conditions with high unmet need through accelerated approval.”
A Novartis spokesperson said that the Swiss drugmaker agrees with ICER’s clinical effectiveness assessment, but disagrees with other aspects of the report, without going into details.
“Overall, sickle cell disease and VOCs are associated with decreased quality of life – including cognitive and social aspects, as well as impact on employment and education for patients and caregivers. Many of these effects can be hard to capture with economic models in sickle cell disease, a critical point that ICER acknowledges.”
Endpoints has also contacted Emmaus for comment.
A final report, incorporating feedback from the companies, patients and providers and an independent panel of stakeholders, is expected to be published by ICER in April.