Orkambi, Symdeko and Kalydeco All of Benefit, But Too Costly to Be of Good Value to Patients, Midwest CEPAC Says

Vertex Pharmaceuticals’ treatments for cystic fibrosis (CF) all provide considerable benefits, but their pricing is not transparent and does not align with the medications clinical value, a review of the Institute for Clinical and Economic Review (ICER)’s report by the Midwest Comparative Effectiveness Public Advisory Council (Midwest CEPAC) decided.

A majority of council members voted that these market price of these therapies “exceed commonly used cost-effectiveness thresholds” and they should be lowered.

ICER’s Final Evidence Report and Report-at-a-Glance on cystic fibrosis transmembrane conductance regulator (CFTR) modulators, the main course of treatment for CF patients, include combo medications like Symdeko (tezacaftor/ivacaftor), Orkambi (lumacaftor/ivacaftor), and the stand-alone therapy Kalydeco (ivacaftor).

Midwest CEPAC held a public meeting to review ICER’s analysis. A majority of the council agreed in a vote that, in their specified indications, Orkambi, Symdeko and Kalydeco when used with best supportive care all provide significant health benefits to CF patients in comparison with best supportive care alone.

In addition to benefits established in the clinical trials, Midwest CEPAC members noted these medications also offer other benefits, including a greater ability to return to work, school, or other activities. They emphasized that these therapies are the first in many years to offer patients marked clinical improvements.

The context of the disease must be taken into account in an analysis of a treatment’s value, the CEPAC members noted, as CF severity is associated with a high lifetime burden of illness.

Still, a majority of council members also agreed with ICER’s finding that the treatments are too costly. They ultimately decided that each of the three therapies carry a “low” long-term value for money, due in large part to their high price. The analysis suggested discounts of up to 77% to align their prices with their clinical value.

Comparing each treatment’s overall value plus supportive care against supportive care alone, 10 of 12 council members found Kalydeco’s value to be low; 11 of 12 for Orkambi; and 11 of 12 voted twice that Symdeco was of “low” comparative value — once for its use in patients homozygous for the F508del mutation, and a second time for those who are “candidates for Symdeko combination therapy because they carry one F508del mutation and residual function mutation” that may respond to this treatment.

Recommended discounts from each treatment’s “wholesale acquisition costs” to reach “value-based benchmark prices” were 72% to 77% for Kalydeco and Symdeco, and 71% to 75% for Orkambi.

“Discussions at our meeting highlighted that, while these therapies offer important benefits for those living with CF, the $300,000 annual price is far too high to pay year after year, harming patients and families today while threatening the health care system’s ability to maintain access to important future clinical advances,” Dan Ollendorf, PhD, ICER’s CSO, said in a press release.

Ollendorf added that while Vertex “should be rewarded for its innovation” as the sole developer of these three medications, it “should also be willing to make their pricing decisions fully transparent, and fully engage in independent, multi-stakeholder assessments of the value of these medications.”

The Cystic Fibrosis Foundation provided financial and scientific support for the development of Symdeko, Orkambi and Kalydeco. Its representative at the meeting noted that the Foundation was not involved in Vertex discussions on pricing.

Following voting, a roundtable of CF families, patient advocates, clinicians, and public and private payers discussed implications for policy and practice. Key recommendations from this discussion include:

• Vertex has significant social responsibility to restrain pricing during its period of monopoly. The company “should abandon vague claims that prices are justified by the need to invest in future research,” and, as an increasing number of other companies already do, provide a transparent justification for its prices “based on the ability of new treatments to improve the length and quality of patients’ lives.”
• Public and private payers should remain committed to give access to relevant clinical advances for CF and should abandon “superfluous requirements for coverage approval and continuation.”
• Patient organizations with a leading role in fostering innovative research “should demand commitments from pharmaceutical manufacturers for sustainable pricing.”
• Professional societies should bear witness “to the impact on their patients of failed pricing and insurance policies,” and engage in public discussions to define pricing by weighing affordability and requirements for future innovation.

Vertex expressed its disappointment with ICER’s report in May. In a letter to ICER, it identified three main flaws: arbitrary choices that did not cover the therapeutic activity of the medications in their full extent, a very review period that did not enable proper presentation of evidence by the CF community, and concerns over ICER’s methodology that could not assess breakthrough treatments for rare diseases, like its CF medications.

“We believe the doctors who care for CF patients — not panels of academics and health economists — should be making treatment decisions for these patients,” Samantha Ventimiglia, vice president of Government Affairs And Public Policy at Vertex, stated in the letter.

“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,” Ventimiglia added. “We object strongly to your intentions to use your flawed results to attempt to remove this broad access for patients with this serious disease.”