U.S. Food and Drug Administration Approves Corcept’s Lifyorli™ (relacorilant) Combination Therapy for Platinum-Resistant Ovarian Cancer
Corcept Therapeutics Incorporated has announced a major regulatory milestone with the approval of its novel therapy, Lifyorli™ (relacorilant), by the U.S. Food and Drug Administration. The drug, used in combination with nab-paclitaxel, is now approved for the treatment of adult patients with platinum-resistant epithelial ovarian cancer, as well as related cancers of the fallopian tube and primary peritoneum. This approval marks a significant advancement in addressing a disease that has historically been difficult to treat, especially in patients who have already undergone multiple lines of therapy.
Lifyorli represents a first-in-class treatment as the first FDA-approved selective glucocorticoid receptor antagonist (SGRA). Its mechanism targets the effects of cortisol, a hormone known to influence tumor progression and resistance to therapy. By modulating cortisol activity, relacorilant introduces a new therapeutic pathway in oncology, opening doors to innovative approaches for cancer management.
Addressing an Unmet Need in Ovarian Cancer
Platinum-resistant ovarian cancer remains one of the most challenging forms of gynecologic malignancies. Patients diagnosed with this condition typically experience disease progression within six months of platinum-based chemotherapy, limiting the effectiveness of standard treatment options. The newly approved Lifyorli combination is specifically indicated for patients who have received one to three prior systemic therapies, including at least one regimen containing bevacizumab.
This targeted patient population has long faced limited options, making the FDA’s decision particularly impactful. By introducing a therapy that improves survival outcomes without requiring biomarker-based patient selection, Lifyorli offers broader accessibility and clinical utility.
Clinical Evidence from the ROSELLA Trial
The FDA’s approval was primarily based on results from the pivotal Phase 3 ROSELLA trial. This global, randomized study enrolled 381 patients diagnosed with platinum-resistant ovarian cancer. Participants had previously received between one and three lines of therapy, ensuring that the study reflected real-world treatment scenarios.
Patients in the trial were randomized in a 1:1 ratio to receive either the combination of Lifyorli plus nab-paclitaxel or nab-paclitaxel alone. Importantly, the study did not require biomarker selection, reinforcing the treatment’s applicability across a wide patient population.
ROSELLA successfully met its dual primary endpoints: progression-free survival (PFS) and overall survival (OS). The results demonstrated a statistically significant and clinically meaningful improvement for patients receiving the combination therapy.
Patients treated with Lifyorli in combination with nab-paclitaxel experienced a 35 percent reduction in the risk of death compared to those receiving nab-paclitaxel alone. The hazard ratio for overall survival was 0.65, with a highly significant p-value of 0.0004. Median overall survival increased to 16.0 months in the combination group, compared to 11.9 months in the monotherapy group—an improvement of 4.1 months.
In addition to overall survival, progression-free survival also improved significantly. The combination therapy reduced the risk of disease progression by 30 percent, with a hazard ratio of 0.70 and a p-value of 0.008. These results were confirmed through blinded independent central review, strengthening the reliability of the findings.
Safety and Tolerability Profile
Beyond efficacy, the safety profile of Lifyorli was a key consideration in its approval. Data from both the ROSELLA trial and earlier Phase 2 studies were pooled to evaluate the drug’s tolerability.
The combination of Lifyorli and nab-paclitaxel was generally well tolerated, with manageable side effects. However, as with many oncology treatments, certain risks were identified and included in the prescribing information. These include warnings related to neutropenia, severe infections, adrenal insufficiency, exacerbation of conditions treated with glucocorticoids, and potential embryo-fetal toxicity.
The most common adverse reactions, observed in more than 20 percent of patients, included decreased hemoglobin levels, reduced neutrophil counts, fatigue, nausea, diarrhea, thrombocytopenia (low platelet count), rash, and decreased appetite. Despite these side effects, the overall safety profile was considered acceptable given the severity of the disease and the limited treatment alternatives.
Scientific and Clinical Recognition
The ROSELLA trial findings have already garnered significant attention within the medical community. Initial results were presented at the 2025 annual meeting of the American Society of Clinical Oncology and were simultaneously published in the prestigious journal The Lancet. These platforms underscore the importance and credibility of the data supporting Lifyorli’s approval.
Further detailed results from the trial are expected to be presented at the upcoming meeting of the Society of Gynecologic Oncology, continuing the momentum of scientific discussion around this new therapy.
Expert Perspectives
Clinical experts have highlighted the significance of Lifyorli’s approval in transforming the treatment landscape for ovarian cancer. According to Dr. Rob Coleman of Texas Oncology and a special advisor to the president of the GOG Foundation, the data demonstrate that the combination therapy provides a meaningful survival benefit while maintaining tolerability. He emphasized that Lifyorli has the potential to become a new standard of care for patients with platinum-resistant ovarian cancer.
Advocacy groups have also welcomed the approval. Sarah DeFeo, Chief Program Officer at the Ovarian Cancer Research Alliance, described the decision as encouraging news for the ovarian cancer community. She acknowledged the contributions of patients, families, and researchers who participated in clinical trials, noting that their efforts were instrumental in advancing this urgently needed treatment option.
Company Vision and Future Directions
From the company’s perspective, this approval represents both a milestone and a starting point. Dr. Joseph Belanoff, Chief Executive Officer of Corcept, expressed pride in bringing a new treatment to patients who have historically had limited options. He highlighted the company’s long-standing commitment to exploring cortisol modulation as a therapeutic strategy in oncology.
Belanoff also emphasized that while the approval of Lifyorli is a major achievement, it is only the beginning of what could be a broader exploration of glucocorticoid receptor antagonism in cancer treatment. Ongoing and future studies are expected to investigate additional indications and combination strategies, potentially expanding the role of this novel mechanism across oncology.
Global Collaboration Behind the Trial
The success of the ROSELLA trial was made possible through extensive international collaboration. The study was conducted across multiple regions, including the United States, Europe, South Korea, Brazil, Argentina, Canada, and Australia.
Several leading research organizations contributed to the trial, including The GOG Foundation, the European Network of Gynaecological Oncological Trial groups (ENGOT), the Asia-Pacific Gynecologic Oncology Trials Group (APGOT), the Latin American Cooperative Oncology Group (LACOG), and the Australia New Zealand Gynaecological Oncology Group (ANZGOG). This global effort ensured diverse patient representation and strengthened the generalizability of the findings.
A Step Forward in Oncology Innovation
The approval of Lifyorli underscores the growing importance of innovative mechanisms in cancer therapy. By targeting the glucocorticoid receptor and addressing the role of cortisol in tumor biology, Corcept has introduced a novel approach that differs from traditional chemotherapy and targeted therapies.
For patients with platinum-resistant ovarian cancer, this development offers renewed hope. With improved survival outcomes, manageable safety, and broad applicability, Lifyorli has the potential to reshape treatment strategies and improve quality of life for many individuals facing this aggressive disease.
As research continues and additional data emerge, the oncology community will be closely watching how this new class of therapy evolves. For now, the FDA’s approval marks a meaningful advancement in the fight against ovarian cancer and a promising step toward more effective, personalized treatment options.
About Ovarian Cancer
Ovarian cancer is the fifth most common cause of cancer death in women. Patients whose disease returns less than six months after receiving platinum-containing therapy have “platinum-resistant” disease. There are few treatment options for these women. Approximately 20,000 women with platinum-resistant disease are candidates to start a new therapy each year in the United States, with at least an equal number in Europe.
About Cortisol’s Role in Oncology
Cortisol plays a role in tumor growth through several mechanisms. It helps solid tumors resist chemotherapy by inhibiting cellular apoptosis — the tumor-killing effect chemotherapy is meant to stimulate. In some cancers, cortisol promotes tumor growth by activating oncogenic signaling in the cells to which it binds. Cortisol also suppresses the body’s immune response, which weakens its ability to fight all diseases, including cancer.
Corcept is developing relacorilant in ovarian, endometrial, cervical, pancreatic and prostate cancers. Relacorilant is proprietary to Corcept and is protected by composition of matter, method of use and other patents. It has been designated an orphan drug by the European Commission (EC) for the treatment of ovarian cancer. Corcept has submitted a Marketing Authorisation Application (MAA) to the European Medicines Agency (EMA) for relacorilant to treat patients with platinum-resistant ovarian cancer.
About Lifyorli™
Lifyorli (relacorilant), approved in combination with nab-paclitaxel, is the first U.S. Food and Drug Administration (FDA)-approved selective glucocorticoid receptor antagonist for adults with platinum-resistant ovarian cancer. Lifyorli is an oral medication taken the day before, the day of and the day after treatment with nab-paclitaxel. There is no biomarker requirement for Lifyorli. Lifyorli competitively binds to the glucocorticoid receptor (GR), where it enhances chemotherapy sensitivity by inhibiting cortisol’s suppression of apoptosis – the programmed cell death that chemotherapies such as nab-paclitaxel are meant to cause. Lifyorli does not have any effect at the body’s other steroid receptors.
