ICER Releases Evidence Report on Treatments for Cystic Fibrosis

Evidence on Trikafta provides high confidence of a substantial net health benefit for patients; additional benefits accrue for family members and society –

– Nonetheless, analyses suggest that the price set by the manufacturer would need to be deeply discounted to align fairly with these benefits and ensure that they are not outweighed by the negative health effects for others resulting from increasing insurance costs –

– Due to COVID-19 concerns, ICER has postponed the public meeting on this topic –

BOSTON, April 27, 2020 – The Institute for Clinical and Economic Review (ICER) today released an Evidence Report assessing the comparative clinical effectiveness and value of elexacaftor/tezacaftor/ivacaftor (Trikafta®, Vertex Pharmaceuticals) for the treatment of cystic fibrosis (CF). ICER also examined new data that have become available since its May 2018 review of three related CF treatments: ivacaftor (Kalydeco®, Vertex), lumacaftor/ivacaftor (Orkambi®, Vertex), and tezacaftor/ivacaftor (Symdeko®, Vertex). All four therapies are CFTR modulators.

“CF is a devastating disease that affects the lungs and other organ systems, typically requires substantial medical care, and robs patients and families of hours each day, before taking away full years of life,” said David Rind, MD, ICER’s Chief Medical Officer. “Kalydeco was a great advance for a small segment of the CF population, and Trikafta appears to be an even more remarkable advance for a much larger segment of the population. Trikafta is likely to alter the course of disease for the majority of patients with CF, transforming their lives and the lives of caregivers. It is critical that all eligible patients be able to access CFTR modulators.

“Despite being transformative therapies, the prices set by the manufacturer – costing many millions of dollars over the lifetime of an average patient – are out of proportion to their substantial benefits. When a manufacturer has a monopoly on treatments and is aware that insurers will be unable to refuse coverage, the lack of usual counterbalancing forces can lead to excessive prices. Patients who receive the treatments will benefit, but unaligned prices will cause significant negative health consequences for many unseen individuals – those throughout society who will experience financial toxicity and may have to delay care, forego care, or even abandon insurance as their out of pocket costs and premiums are driven upward.”

Key Clinical Findings

Trikafta earned ICER’s highest “A” evidence rating: for the indicated populations where clinical data exist, the evidence provides high certainty that Trikafta provides a substantial net health benefit over standard care and over Symdeko. In addition, although Trikafta has not yet been studied in patients who are heterozygous for the F508del mutation and a residual function mutation, ICER determined that using Trikafta to treat that sub-population is likely to be at least as good as treating with Symdeko, and possibly better.

For the other three related treatments – Symdeko, Orkambi, and Kalydeco – ICER’s evaluation of new evidence since our 2018 assessment confirms our previous evidence ratings. For their respective indicated populations, and compared to best supportive care, the evidence provides high certainty that Kalydeco provides a substantial net health benefit, Orkambi provides a small net health benefit, and Symdeko provides at least a small net health benefit with the potential for a substantial benefit.

Potential Other Benefits and Contextual Considerations

In addition to the demonstrated clinical effectiveness, policymakers should be aware of the other potential benefits and contextual factors associated with these diseases. Throughout ICER’s eight-month review, patients shared their personal stories about how CF affects all aspects of their lives. Patients and caregivers described how CF robs them from being able to spend time with family and friends, pursue educational and professional opportunities, and plan for the future. Patients also shared how much Trikafta, Symdeko, Orkambi, and Kalydeco have helped them be more active, spend more time with family and friends, and plan for the future in a way that would have been unthinkable just a few years ago.

In addition, ICER’s report notes that decision-makers often give special considerations to therapies for ultra-rare diseases that may lead to coverage and funding decisions at higher thresholds for cost-effectiveness. Based on the size of their respective indicated populations, Kalydeco, Orkambi, and Symdeko all meet ICER’s definition of a treatment for an ultra-rare condition. However, due to its broader label and a potential US patient population greater than 10,000 individuals, Trikafta does not meet ICER’s definition as a treatment for an ultra-rare condition.

Key Cost-Effectiveness Findings

ICER’s recommended health-benefit price benchmark (HBPB) for Trikafta is $67,900-$85,500 per year, which would require at least a 73% discount off the treatment’s current list price.

The HBPB is a price range suggesting the highest US price a manufacturer should charge for a treatment, based on the amount of improvement in overall health patients receive from that treatment, when a higher price would cause disproportionately greater losses in health among other patients in the health system due to rising overall costs of health care and health insurance. In short, it is the top price range at which a health system can reward innovation and better health for patients without doing more harm than good.

Public Comments and Evidence Appraisal

Due to public health concerns regarding meetings and travel during the ongoing COVID-19 situation, ICER is postponing our CF public meeting indefinitely.

A draft version of this report was previously open for a five-week public comment period. The updated Evidence Report reflects changes made based on comments received from patient groups, clinicians, drug manufacturers, and other stakeholders. Detailed responses to public comments can be found here.

About ICER

The Institute for Clinical and Economic Review (ICER) is an independent non-profit research institute that produces reports analyzing the evidence on the effectiveness and value of drugs and other medical services. ICER’s reports include evidence-based calculations of prices for new drugs that accurately reflect the degree of improvement expected in long-term patient outcomes, while also highlighting price levels that might contribute to unaffordable short-term cost growth for the overall health care system.

ICER’s reports incorporate extensive input from all stakeholders and are the subject of public hearings through three core programs: the California Technology Assessment Forum (CTAF), the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC), and the New England Comparative Effectiveness Public Advisory Council (New England CEPAC). These independent panels review ICER’s reports at public meetings to deliberate on the evidence and develop recommendations for how patients, clinicians, insurers, and policymakers can improve the quality and value of health care. For more information about ICER, please visit ICER’s website.