The approved CFTR modulators developed by Vertex Pharmaceuticals are too expensive for the clinical benefit they can provide to cystic fibrosis (CF) patients, according to the Institute for Clinical and Economic Review (ICER).
ICER evaluated the effectiveness and costs of Symdeko (tezacaftor/ivacaftor), Orkambi (lumacaftor/ivacaftor), and Kalydeco (ivacaftor) in comparison with best supportive care available for three distinct populations representative of main genetic mutations involved in CF.
A preliminary version of the report was previously open to public comment in order to allow coverage and inclusion of CF population thoughts about these targeted therapies. Detailed responses to public comments can be found here.
The report states that Kalydeco can provide significant benefits for patients who have gating and residual function mutations. In contrast, the review board found that Orkambi and Symdeko could provide only small and small-to-substantial net health benefits to patients with two copies of the F508del mutation in the CFTR gene (the gene that is defective in CF).
For patients with one copy of the F508del mutation and an additional residual function variant, the analysis revealed that Symdeko could provide small-to-substantial benefits.
Analysis of the drug’s costs showed that for all CF sub-populations analyzed, they far exceeded the value that is commonly accepted as the thresholds for cost-effectiveness, which is of $100,000-$150,000 per quality-adjusted life year gained.
To align the financial burden of these therapies with the clinical benefit reported, ICER members recommended the net prices should be reduced 71 to 77%.
Despite this not-so-positive evaluation, the review board noted that decision-makers often accept higher thresholds for cost-effectiveness for therapies that target rare diseases, such as CF.
“Our report summarizes the evidence demonstrating that CFTR modulator therapies, paired with best supportive care, provide clinical benefit for patients who have not been treated previously with disease-modifying therapy,” Dan Ollendorf, PhD, chief scientific officer of ICER, said in a press release. “The current prices for these drugs, however, produce overall costs that are far in excess of those needed to reach commonly cited cost-effectiveness thresholds.”
ICER’s final Evidence Report will be the subject of a public discussion May 17 during the Midwest Comparative Effectiveness Public Advisory Council meeting (CEPAC) in St. Louis, Missouri. The study will provide the basis for the development of treatment recommendations to be applied for policy and clinical practice in order to improve the quality and value of healthcare.
Registration to attend the Midwest CEPAC meeting or to view the live webcast is now open.
“Our public meeting will bring stakeholders together to discuss strategies to achieve sustainable patient access to these therapies while supporting the innovation that will bring further progress in treating diseases like CF,” Ollendorf said.
In a letter to ICER, Vertex has shown its disappointment towards ICER’s report. The company identifies three main flaws in the review process, which they believe have conditioned the cost-effectiveness findings of the review board.
First, they believe ICER’s analysis methods are based in several arbitrary choices that fail to cover the therapeutic activity of the drugs in their full extent. Omission of information, such as the fact that these therapies are the first to treat the underlying cause of CF, consequently will lead to worse outcomes.
Also, the company considers that the timeline of the review process did not respect the CF community, leaving a very short period of time for patients, physicians, and the company to prepare and present their evidence.
Finally, Vertex believes that over the last seven months ICER has ignored several concerns raised by the CF community on the methodology used and its inability to evaluate breakthrough orphan drugs for CF.
Taken together, these flaws culminate in what the company describes as an “attempt to remove the broad access” to these CF therapies.
“Today, CF patients in the United States have broad access to Kalydeco, Orkambi, and Symdeko, which address the underlying cause of their devastating disease. Both public and private payers have universally recognized their clinical value. We object strongly to your intentions to use your flawed results to attempt to remove this broad access for patients with this serious disease,” Samantha Ventimiglia, vice president of Government Affairs And Public Policy at Vertex, stated in the letter to ICER.
“We believe the doctors who care for CF patients — not panels of academics and health economists — should be making treatment decisions for these patients,” Ventimiglia said, adding that the company’s “focus and efforts will remain on honoring our commitment to the CF community — to develop more new breakthrough medicines and ultimately a cure for this devastating disease, and to ensure that all eligible patients will have equal access to these treatments.”