ICER Issues Final Report and Policy Recommendations on Treatments for Cystic Fibrosis

— Independent appraisal committee unanimously concludes that Trikafta delivers substantial benefits for patients, 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 health care costs —

BOSTON, September 23, 2020 – The Institute for Clinical and Economic Review (ICER) today released a Final Evidence Report and Report-at-a-Glance 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. ICER’s report on these therapies was reviewed at the August 2020 public meeting of the California Technology Assessment Forum (CTAF), one of ICER’s three independent evidence appraisal committees. Vertex was invited to share the company’s perspective at the public meeting but declined to participate.

“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. “Trikafta is a remarkable advance for the majority of people living with CF, and we encourage public and private US payers to maintain a simple process for all eligible patients to access this important treatment. Unfortunately, the manufacturer has leveraged its monopoly to set a price — costing many millions of dollars over the lifetime of an average patient — that is far out of proportion to the treatment’s substantial benefits. Patients who receive Trikafta will benefit, but misaligned pricing causes harm to patients — some with CF and some with other diseases — who are forced to delay or forego care or even to drop health insurance entirely.”

ICER’s leadership expanded upon this dual need for fair access and fair pricing in an open letter to the CF community.

Voting on Clinical Effectiveness and Contextual Considerations

For all patient sub-populations for whom published evidence exists, Trikafta earned ICER’s highest “A” evidence rating. During the public meeting, CTAF members voted unanimously that, for individuals with CF who are homozygous for the F508del mutation, the evidence is adequate to demonstrate that Trikafta is superior to either Symdeko or best supportive care alone. For individuals with CF who are heterozygous for the F508del mutation with a residual function mutation, CTAF members voted that the evidence was adequate to show Trikafta is superior to best supportive care alone, but a slight majority (8-6) voted that the current published evidence is inadequate to demonstrate Trikafta’s superiority over Symdeko. For individuals with CF who are heterozygous for the F508del mutation with a minimal function mutation, all panelists found that Trikafta is superior to best supportive care alone.

During their deliberation, panel members also weighed Trikafta’s other benefits and contextual considerations. All recognized that CF is a severe disease that significantly affects patients’ length and quality of life. While a majority of panelists noted uncertainty around Trikafta’s long-term benefits and side-effects, they also found that the treatment will significantly improve patients’ ability to return to work, reduce caregiver or broader family burden, and have a positive impact outside the family. The panelists also noted Trikafta’s status as the first therapy that can treat the underlying cause of CF for a large portion of these patients.

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.

Key Cost-Effectiveness Findings

Consistent with ICER’s methodology, the CTAF did not vote on Trikafta’s long-term value for money because, at its current price, the treatment far exceeds commonly cited thresholds for cost-effectiveness. 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.

Access and Affordability Alert

ICER is issuing an Access and Affordability Alert for Trikafta. Throughout ICER’s review, clinical expert input suggested that all eligible patients receive a CFTR modulator, and that most patients and clinicians would be likely to switch from previous treatments to Trikafta. Assuming all eligible patients who are already on an older CFTR modulator transition to Trikafta, only 35% of newly eligible patients could be treated with Trikafta at its current list price before crossing ICER’s potential budget impact threshold of $819 million per year.

The purpose of an ICER Access and Affordability Alert is to signal to stakeholders and policy makers that the amount of added health care costs associated with a new service may be difficult for the health system to absorb over the short term without displacing other needed services or contributing to rapid growth in health care insurance costs that threaten sustainable access to high-value care for all patients.

Key Policy Recommendations  

Following the voting session, a policy roundtable of experts — including clinical experts, patient advocates, and representatives from public and private payers — convened to discuss the implications of the evidence for policy and practice. Key recommendations stemming from the roundtable discussion include:

  • Despite concerns about the price of these treatments, public and private payers should continue to affirm their commitment to provide access to CFTR modulators and should remove superfluous requirements for coverage approval and continuation. Prior authorization criteria for Trikafta should be based on clinical evidence, specialty society guidelines, and input from clinical experts and patient groups.
  • The manufacturer, which has benefitted from monopoly pricing power, should lower the price of Trikafta to align fairly with its demonstrated benefits. Pricing treatments within a proportional level to their benefits allows a health system to reward innovation and improve access to patients.
  • There should be greater support for the groundbreaking studies initiated and funded by the Cystic Fibrosis Foundation. Future studies should measure and report a broad set of outcomes to better assess the health and economic impact of CF interventions to patients, their caregivers, and their health system. Large studies with long term follow-up are needed to complement the short-term results observed in the pivotal randomized trials, and patients who are heterozygous of the F508del mutation and a residual function mutation should be prioritized in future research.
  • Patient organizations that have a leading role in funding, organizing, promoting, and otherwise fostering innovative research on new treatments should demand commitments from manufacturers for sustainable pricing of the products patients helped bring to the market. Similarly, professional societies should fully exercise their responsibility by bearing witness to the impact on their patients of failed pricing and insurance policies.

ICER’s detailed set of policy recommendations, including considerations for establishing prior authorization criteria, is available in the Final Evidence Report and in the standalone Policy Recommendations document.

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.