FDA Clears Corcept’s Lifyorli™ (relacorilant) in Combination with Nab-Paclitaxel for Platinum-Resistant Ovarian Cancer Treatment
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. This approval marks a significant advancement in the treatment landscape for patients suffering from difficult-to-treat gynecologic cancers, particularly those with platinum-resistant disease. The newly approved regimen combines Lifyorli with nab-paclitaxel and is indicated for adults diagnosed with platinum-resistant epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who have previously undergone one to three lines of systemic therapy, including at least one regimen containing bevacizumab.
Lifyorli represents a breakthrough in oncology therapeutics as the first FDA-approved selective glucocorticoid receptor antagonist (SGRA). This innovative class of drugs works by modulating the activity of cortisol, a hormone known to influence tumor biology, immune response, and resistance to chemotherapy. By selectively targeting the glucocorticoid receptor, relacorilant offers a novel mechanism to enhance the effectiveness of cytotoxic therapies such as nab-paclitaxel, potentially overcoming resistance mechanisms that limit the efficacy of existing treatments.
The FDA’s decision was primarily supported by robust data from the pivotal Phase 3 ROSELLA clinical trial. This large-scale, randomized study enrolled 381 patients diagnosed with platinum-resistant ovarian cancer across multiple global sites. All participants had previously received between one and three lines of therapy, including bevacizumab. Importantly, the trial did not require biomarker-based patient selection, underscoring the broad applicability of the treatment across a diverse patient population.
Participants in the ROSELLA study were randomized in a 1:1 ratio to receive either the combination of Lifyorli and nab-paclitaxel or nab-paclitaxel alone, which served as the control arm. The trial successfully met its dual primary endpoints: progression-free survival (PFS) and overall survival (OS), both of which are critical indicators of treatment benefit in oncology trials.
The results demonstrated a statistically significant and clinically meaningful improvement in survival outcomes for patients receiving the combination therapy. Specifically, the addition of Lifyorli led to a 35 percent reduction in the risk of death compared to nab-paclitaxel alone, with a hazard ratio of 0.65 and a highly significant p-value of 0.0004. Median overall survival was extended to 16.0 months in the combination arm, compared to 11.9 months in the monotherapy group, representing a notable improvement of 4.1 months.
In addition to overall survival benefits, the study also showed a 30 percent reduction in the risk of disease progression among patients treated with the combination therapy. This was measured through blinded independent central review (PFS-BICR), with a hazard ratio of 0.70 and a p-value of 0.008. These findings highlight the dual benefit of the regimen in both delaying disease progression and extending patient survival.
Safety and tolerability were also key considerations in the evaluation of Lifyorli. The combination of relacorilant with nab-paclitaxel was found to have a manageable safety profile. The safety analysis included pooled data from both the ROSELLA trial and an earlier Phase 2 study. While the treatment was generally well tolerated, the prescribing information includes important warnings and precautions.
These include risks of neutropenia and severe infections, adrenal insufficiency, exacerbation of conditions typically treated with glucocorticoids, and potential embryo-fetal toxicity. The most commonly reported adverse reactions—occurring in more than 20 percent of patients—included decreased hemoglobin levels, reduced neutrophil counts, fatigue, nausea, diarrhea, thrombocytopenia, rash, and decreased appetite. These side effects are consistent with those commonly observed in oncology regimens and were considered manageable with appropriate clinical monitoring and supportive care.
The initial findings from the ROSELLA trial were first presented at the prestigious American Society of Clinical Oncology Annual Meeting in 2025 and were simultaneously published in the renowned medical journal The Lancet. Further detailed results are scheduled to be presented at the upcoming meeting of the Society of Gynecologic Oncology, providing additional insights into the clinical benefits and long-term outcomes associated with this therapy.
Clinical experts have responded positively to the approval. Rob Coleman, a leading oncologist affiliated with Texas Oncology and a special advisor to the president of the GOG Foundation, emphasized the importance of this development. He noted that the combination of Lifyorli and nab-paclitaxel delivers a meaningful improvement in overall survival while maintaining a tolerable safety profile. According to him, this positions the regimen as a potential new standard of care for patients with platinum-resistant ovarian cancer, a population that has historically faced limited treatment options and poor prognoses.
Patient advocacy groups have also welcomed the approval. Sarah DeFeo, Chief Program Officer at the Ovarian Cancer Research Alliance, highlighted the significance of expanding treatment options for patients battling this aggressive disease. She expressed gratitude to the patients, families, clinicians, and researchers who contributed to the clinical trials, emphasizing the collaborative effort required to bring new therapies to market.
From a corporate perspective, Joseph Belanoff, Chief Executive Officer of Corcept, described the approval as a milestone achievement. He underscored the company’s long-standing commitment to exploring cortisol modulation as a therapeutic strategy in oncology. While celebrating the approval of Lifyorli as an important first step, he also pointed to the broader potential of this mechanism in treating other cancers and disease areas.
The ROSELLA trial itself was a global effort, enrolling patients across the United States, Europe, South Korea, Brazil, Argentina, Canada, and Australia. The study was conducted in collaboration with several leading oncology research organizations, including the GOG Foundation, the European Network of Gynaecological Oncological Trial groups, the Asia-Pacific Gynecologic Oncology Trials Group, the Latin American Cooperative Oncology Group, and the Australia New Zealand Gynaecological Oncology Group. This extensive collaboration underscores the global urgency of addressing platinum-resistant ovarian cancer and the importance of international partnerships in advancing cancer research.
Overall, the FDA approval of Lifyorli in combination with nab-paclitaxel represents a meaningful advancement in the treatment of platinum-resistant ovarian cancer. By introducing a first-in-class SGRA with demonstrated survival benefits, Corcept has opened a new therapeutic avenue that could reshape clinical practice and improve outcomes for patients facing this challenging diagnosis.
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.
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