Curiosity grows on reasons for delayed permit of Trodelvy

Although the first Trop-2 targeted agent Trodelvy (sacituzumab govitecan), keeps its indications globally, its domestic approval is being delayed, drawing the industry’s attention to its reasons.

Gilead announced last Friday (local time) that Trodelvy had won approval from the U.S. FDA to treat patients with inoperable, locally progressive or metastatic hormone receptor-positive, human epidermal growth factor receptor (EGFR) 2 negative (HR+/HER2-) breast cancer, who also have been treated with endocrine therapy and at least two systemic therapies.

Trodelvy is the first-in-class Trop-2, or tumor-associated calcium single transducer2 (TACSTD2), antibody-drug conjugate developed by Immunomedics that has become a subsidiary of Gilead later. Acquiring Immunomedics, Gilead put Trodelvy at the front of its anti-cancer division.

In April 2020, Trodelvy won the first U.S. approval to treat “triple-negative breast cancer with a previous history of treatment. A year later, the drug expanded its indication to treating locally progressive or metastatic bladder cancer previously treated with platinum-based chemotherapy and anti-PD-(L)1 antibodies.

The third expansion of Trodelvy’s indication was based on the result of phase 3 clinical trial, the TROPiCS-02 study.

In the study, Trodelvy confirmed it could improve statistically significant progression-free survival (PFS) and overall survival (OS) compared to single-agent chemotherapy picked as the control drug by medical workers.

The Trodelvy group’s median PFS (mPFS) was 5.5 months, reducing disease progression and death risks by 34 percent compared to the control group. It also extended median OS (mOS) to 14.4 months, longer by 3.2 months, or 21 percent, than the control group’s 11.1 months.

“Despite progress for decades, HR+/HER2- metastatic breast cancer patients with many previous treatment experiences need new treatment options,” said Dr. Hope S. Rugo of the UCSF Helen Diller Family Comprehensive Care Center who led the TROPiCS-02 study. “That is because most patients of this type become resistant to endocrine therapy and are eventually forced to proceed with the available chemotherapy.

Dr. Rugo went on to say, “The latest approval is very significant, considering that treatment options are limited for patients who have received both endocrine therapy and chemotherapy and that the treatment options that demonstrated a clinically significant survival benefit of more than three months along with the quality of life benefits for these patients are even more extraordinary.”

In Korea, the Ministry of Food and Drug Safety designated Trodelvy as a rare drug to treat triple-negative breast cancer in May 2021.

Everest Medicines, which had the domestic sales right of Trodelvy, did not immediately apply for its fast-track review that became possible with the designation as a rare drug. The Chinese company submitted its application in 2022 after establishing its Korean offshoot, Everest Medicines Korea.

But an unexpected variable occurred in the latter half of 2022.

Immunomedics, the original developer, retrieved Trodelvy's Asian copyright from Everest Medicine, and Gilead took charge of Trodelvy’s global marketing, including in Korea.

Initially, Everest Medicines Korea expected the domestic approval of Trodelvy to be possible toward the end of 2022. However, the approval process's progress is unknown after the copyright change.

According to sources, Everest Medicines Korea was supposed to hand over the sales right to Gilead after completing the approval process with the food and drug safety ministry. However, Trodelvy's permission is delayed more than initially expected, and both companies remain silent about why.

Gilead's Korean office is reportedly setting up a new anti-cancer division and preparing to sell Trodelvy in Korea. According to an industry executive, Gilead expects to win approval in the first half-year.