First FRα-targeted ADC Elahere approved for ovarian cancer

First new mechanism commercialized in a decade… shows improvements in key efficacy endpoints

Biomarker-driven personalized therapy expected to reshape the treatment paradigm

The antibody–drug conjugate (ADC) class has entered the ovarian cancer field, signaling a potential shift in the treatment paradigm.

On the 28th, AbbVie Korea held a press briefing at the Plaza Hotel in Jung-gu, Seoul, to mark the approval of Elahere (mirvetuximab soravtansine) in Korea.

Elahere was approved last month for the treatment of high-grade serous epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer that is folate receptor alpha (FRα) positive and resistant to platinum-based chemotherapy, in patients who have previously received one to three prior systemic therapies before the 19th of last month.

Jung-yun Lee, Professor of Obstetrics and Gynecology, Severance Hospital

Elahere is an ADC targeting FRα-positive ovarian cancer. Its mechanism involves delivering the potent cytotoxic drug DM4 directly into cancer cells to destroy the tumor.  The drug is drawing particular attention as a new option for patients with ovarian cancer who have developed resistance to platinum-based chemotherapy.

Patients with platinum-resistant ovarian cancer often have compromised systemic health due to cumulative toxicity from repeated prior treatments and comorbidities. Therefore, effective later-line treatment options are crucial. However, existing standard treatments like non-platinum-based chemotherapy or certain targeted therapies have shown limited clinical benefits, with low response rates and no statistically significant improvement in survival.

In clinical studies, Elahere reduced the risk of disease progression or death by 35% compared with standard non-platinum chemotherapy.

The median progression-free survival (PFS) was 5.62 months, an improvement over 3.98 months in the control group. The objective response rate (ORR) reached up to 42.3%, significantly higher than 15.9% observed with standard therapy. The median overall survival (OS) was 16.85 months, versus 13.34 months in the control group, corresponding to a 32% reduction in the risk of death.

From a safety perspective, the majority (88%) of adverse events observed in the Elahere treatment group were low-grade and manageable.

The Korean Society of Gynecologic Oncology (KSGO) guidelines recommend Elahere for the treatment of FRα-positive platinum-resistant ovarian cancer with the highest level of evidence (Level I) and strongest recommendation grade (Grade A).

Jung-yun Lee, Professor of Obstetrics and Gynecology, Severance Hospital, who participated in the pivotal clinical trial, stated, “Elahere demonstrated meaningful improvements across key clinical endpoints in platinum-resistant ovarian cancer, an area with high unmet medical need. It also showed consistent efficacy across subgroups. With an ORR of 42.3%, which is higher than that of the control group, Elahere offers the possibility of improved outcomes even for patients who previously had limited expectations of response. It is the first FRα-targeted therapy to demonstrate an overall survival benefit.”

Importance of biomarker testing rises in ovarian cancer

Professor Jae-kwan Lee, Korea University Guro Hospital, Department of Obstetrics and Gynecology

With the approval of Elahere, biomarker-driven personalized treatment strategies are now being more fully implemented in ovarian cancer, raising expectations for meaningful changes in the treatment paradigm.

While targeted therapies in ovarian cancer were previously limited to those based on the expression of a few biomarkers like PARP and HER2, the emergence of Elahere has highlighted the importance of FRα biomarker testing.

FRα is a protein involved in tumorigenesis and is minimally expressed in normal tissues but highly expressed in ovarian cancer.

Approximately 35-40% of all ovarian cancer patients are reported to be FRα-positive. Its expression tends to remain consistent from diagnosis through recurrence, enabling personalized targeted therapy when the cancer progresses to platinum-resistant ovarian cancer.

This biomarker is determined positive when membrane staining intensity of 2+ or higher is confirmed in at least 75% of tumor cells using Roche Diagnostics' immunohistochemistry (IHC)-based companion diagnostic assay.

Professor Jae-kwan Lee of the Department of Obstetrics and Gynecology at Korea University Guro Hospital said, “Depending on tumor heterogeneity, even cases previously negative for FRα may become positive upon recurrence. For patients without treatment alternatives, retesting should be considered.”