Astellas Pharma Korea is continuing complex calculations for health insurance reimbursement listing of its metastatic urothelial cell carcinoma drug Padcev (enfortumab vedotin) in Korea.

The reimbursement is being discussed for the second-line monotherapy indication, which was first approved. However, as the company is seeking reimbursement for the potentially high-impact Keytruda+Padcev combination therapy, more factors remain in need of consideration.


According to industry sources, Astellas Pharma Korea is planning to file a reimbursement application for the Keytruda+Padcev combination therapy as a first-line treatment for urothelial cancer later this year.

The clinical value of the combination is unquestionable, as it is already raising expectations as a treatment that will change the first-line treatment paradigm of urothelial cancer in 30 years.

“Recently, a variety of innovative new drugs have emerged in urothelial cancer, and Padcev is the first new ADC drug for metastatic urothelial cancer that has settled as a new first-line standard of care option in 30 years,” said In-Keun Park, Professor of Medical Oncology at Asan Medical Center in Seoul. “The drug is driving a major shift in treatment strategy, and global guidelines recommend Padcev as the only first-line option for the treatment of urothelial cancer.”

The challenge is that this paradigm-shifting option for first-line treatment of metastatic urothelial cancer is a combination therapy. The combination of Astellas' Padcev and MSD's Keytruda requires coordination between the two companies.

According to industry sources, Astellas does not need MSD's consent to apply for reimbursement for the Padcev+Keytruda combination, because Astellas is only seeking reimbursement for Padcev part of the combination.

This means that Astellas will have to apply for Padcev’s reimbursement in the Padcev+Keytruda combination and wait to see how the situation develops.

Currently, there is no clear track for partial reimbursement of combination therapy, and further discussions will depend on whether the Health Insurance Review and Assessment Service decides to consider the benefits of the combination on a case-by-case basis and grant partial coverage, or whether it will consider reimbursing Keytruda as well.

“Just as the combination therapy of Padcev+Keytruda was approved and the label was separately updated by each pharmaceutical company, the reimbursement does not need to be discussed between the companies,” said an industry insider. “The reimbursement application contains sensitive information about each company, such as the way each drug’s reimbursement is listed and the drug price, so the process needs to be done separately rather than discussed between the 2 companies.”

He added, “While there is a precedent for Imfinzi, it is difficult to predict how the government will approach the Padcev+Keytruda combination.”

However, in this case, MSD's willingness to reimburse its part became important because the reimbursement of only half of the combination is impractical. According to industry sources, MSD has also been having internal discussions about applying for reimbursement for the Padcev+Keytruda combination.

For Astellas, the extent to which MSD is willing to focus on reimbursement in the future will serve as a variable, especially as there are concurrent reimbursement applications for Keytruda monotherapy in progress other than the one for the Padcev+Keytruda combination.

Drug price negotiations and other variables remain for Padcev’s pending second-line reimbursement

Another concern for Astellas is the delay in reimbursement discussions for Padcev’s reimbursement in the second line.

Padcev passed HIRA’s Cancer Disease Review Committee in February but was unable to cross the threshold of the Drug Reimbursement Evaluation Committee, due to DREC’s request for supplementary data.

In addition, even if the drug passes DREC review in the future, it will take more time for the drug to be added to the reimbursement list due to drug price negotiations.

As the insurance drug price set for the second line could serve as a reference point when the company seeks to extend the drug’s coverage to first-line treatment, the government and the company may have different views at the drug price negotiation stage.

One thing to look forward to is that Padcev qualifies as an innovative new drug in Korea. Recently, HIRA established a new flexible ICER threshold for innovative new drugs.

“Since (the combination therapy) is a new type of reimbursement model, we are internally discussing which method will be the fastest and most effective,” said Kyung-ah Park, Director of Medical Affairs at Astellas Korea. “We see it as our responsibility to reimburse Padcev and are actively working on it, and as Padcev meets the three criteria as a Korean innovative new drug, we plan to improve access through reimbursement as soon as possible.