This article has been updated to include a statement from AstraZeneca and Daiichi Sankyo and more details about NICE's severity modifier.
NEW YORK – The National Institute for Health and Care Excellence in England said on Tuesday that it hasn't reached an agreement with AstraZeneca and Daiichi Sankyo on a fair price for Enhertu (trastuzumab deruxtecan), and consequently the institute will maintain its earlier negative appraisal and not recommend the HER2-targeted breast cancer drug as a treatment for advanced HER2-low breast cancer with NHS England.
In preliminary decision in March, NICE said that while the available evidence suggests Enhertu is a significant advance for patients with HER2-low breast cancer, who otherwise have no targeted treatment and limited chemotherapy options, the institute's cost-effectiveness analysis determined that the price drugmakers were asking NHS to pay was too high for the benefits it would provide.
AstraZeneca and Daiichi Sankyo could appeal that earlier final draft guidance, and it seems that the companies did engage in lengthy discussions with NICE, but in the end, the parties didn't agree on price. The list price of Enhertu is £1,455 ($1,843.20) per 100 mg vial, which amounts to £118,000 for a year's supply, but NICE, AstraZeneca, and Daiichi Sankyo were negotiating to offer it an undisclosed discount to the NHS. About 1,000 women with HER2-low breast cancer in England and Wales would have been eligible for Enhertu had NICE recommended it.
NICE Chief Executive Samantha Roberts expressed disappointment that the institute and drugmakers were unable to come to a pricing agreement. "As we've always made clear, the fastest and only guaranteed way to get medicines like Enhertu to the patients who need them is for companies to offer a fair price," Roberts said in a statement. "We have done all we can to try and achieve that."
In its talks with drugmakers, NICE and NHS England offered "as much flexibility as possible," the institute said in a statement, adding that even Wes Streeting, UK's secretary of state for health, intervened. Still, "the companies did not put forward a cost-effective price that would have enabled NICE to recommend Enhertu as value for money for the taxpayer," the organization said in a statement.
NICE highlighted that its inability to recommend Enhertu breaks a six-year streak, during which it has been able to come to a pricing agreement on and issue positive recommendations for 21 breast cancer treatments that came before it. Earlier this year, for example, NICE issued a positive recommendation for Pfizer's Talzenna (talazoparib) for treating HER2-negative advanced breast cancer, which it reviewed using the same methods as Enhertu, including a framework that places greater weight on drugs for severe diseases.
NICE shifted to using a "severity modifier" from an "end of life" modifier in gauging the value of medicines as part of a 2022 update to its health technology assessment methodology. The institute has maintained that applying a severity modifier, which gives higher weighting to drugs based on the severity of the disease they treat (high, medium, or none), has allowed it to issue more positive recommendations than it has historically using an end-of-life modifier.
However, over the summer, amid signs that the drugmakers and NICE would not be able to come to an agreement on Enhertu's price, AstraZeneca CEO Pascal Soriot told multiple media outlets that he was disappointed in NICE's decision and criticized the organization's review methodology as disadvantaging advanced cancer therapies.
A spokesperson representing AstraZeneca and Daiichi Sankyo said in a statement that the new NICE severity modifier "misclassifies HER2-low metastatic breast cancer as a ‘medium severity’ disease," and that "this stands in the way of patient access in England, Wales, and Northern Ireland." The companies also charged that "NICE has acknowledged that the design of its severity modifier will see patients with metastatic cancer lose out" and expressed concern that the institute's upcoming research into societal preferences will take two years to wrap up.
"This is too long to wait for patients, especially when there are simple changes that could be made here and now," the spokesperson said. "We are calling on NICE to evolve the way treatments are assessed for patients in England and Wales to create a system that enables equitable access for patients in line with other countries."
Enhertu is approved in more than 40 countries including the US, several EU countries, and China for patients with unresectable metastatic HER2-low breast cancer who have had prior systemic therapy or disease recurrence during adjuvant chemotherapy or within six months of completing adjuvant chemotherapy.
"We are very disappointed by, and disagree with, the decision NICE has made," the spokesperson for the drugmakers continued. "Nineteen other European countries, including Scotland and most recently Spain and Romania, have already delivered routine patient access to trastuzumab deruxtecan for HER2-low metastatic breast cancer patients."
Evidence supporting the use of Enhertu in patients with HER2-low metastatic breast cancer comes from the Phase III DESTINY-Breast04 trial, in which the risk of disease progression or death was reduced by 50 percent for patients receiving Enhertu compared to physician's choice of chemotherapy. Median progression-free survival was 9.9 months for the Enhertu group compared to 5.1 months for those on chemotherapy.
"We remain committed to finding a way forward for patients – one that appropriately recognises the severity of this disease and the value of the medicines that target it," the spokesperson said.