Japan’s Health Ministry warned that Eli Lilly’s breast cancer therapy Verzenio (abemaciclib) might adversely affect the lungs. The U.S. pharmaceutical firm won approval for the same drug in Korea on May 1.
The Ministry of Food and Drug Safety (MFDS)’s approval condition for Verzenio states that the treatment should be a primary endocrine therapy for postmenopausal women with HR+/ HER2-progressive or metastatic breast cancer. The drug is also authorized to be used in combination with an aromatase inhibitor, or with fulvestrant to treat HR+/HER2-progressive or metastatic breast cancer with the disease advanced after endocrine therapy.
Industry watchers expect that it will take some time for Lilly Korea to release Verzenio in the local market. However, the safety issue could linger even after a product launch, and how Lilly Korea will ensure the safety of Verzenio will be significant, they said.
On Friday, Japan’s Health Ministry said 14 patients treated with Verzenio developed serious lung diseases, and three of them died.
The ministry said the drug is suspected of causing adverse drug reactions in at least four cases including one fatality among the 14 cases and ordered Eli Lilly to include a new warning on the precaution label of the treatment.
Lilly obtained approval for Verzenio in Japan in September 2018 and rolled out the drug there in November. Verzenio is reported to have been used for over 2,000 patients to date.
“Even though we received the nod for Verzenio from the MFDS in Korea, we are undergoing procedures for reimbursement. We have several months left to release the drug in the domestic market,” Lilly Korea said. “In the wake of the Health Ministry’s announcement, we are reviewing the side effects reported during local clinical trials. We will discuss with the MFDS for further scheduling.”
The clinical trials, which were the basis of both Japanese and Korean approval, included a similar ratio of Koreans and Japanese patients, raising safety concerns for Koreans as well.
MONARCH 2 trial, the key study on Verzenio, was a global, phase-3 trial that compared the Verzenio plus fulvestrant combo with the fulvestrant monotherapy in patients with HR+/HER2-progressive or metastatic breast cancer with the disease advanced after endocrine therapy.
Among 669 patients who participated in the MONARCH 2 study, 178 came from North America, 279 from Europe, 39 from Thailand, 95 from Japan, and 78 from Korea.
Lilly won the Verzenio license in most of these countries based on the study.
Lilly announced the outcome of MONARCH 2 on an American oncology journal in September 2017. The research team said 14 from the Verzenio-treated group, and 10 from the control group died.
“Among the 14 cases of death in the Verzenio group, three deaths in the abemaciclib arm were determined to be related to the study treatment; two were due to sepsis in patients in whom guidance regarding granulocyte colony-stimulating factor administration and dose reduction was not followed, and one was due to viral pneumonia in a patient receiving steroids for spinal stenosis,” the researchers said.
According to MONARCH 2’s serious adverse events on ClinicalTrials.gov, Verzenio had more side effects related to infections, viral pneumonia, and sepsis than the control drug. MONARCH 1 to 3 studies also reported deaths related to lung diseases, including pneumonitis.