On March 25, 2026, the FDA approved relacorilant (Lifyorli, Corcept Therapeutics), a selective glucocorticoid receptor antagonist, in combination with nab-paclitaxel for adults with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic regimens, at least one of which included bevacizumab. This represents the first FDA approval of a selective glucocorticoid receptor antagonist for cancer and introduces a novel systemic mechanism for platinum-resistant ovarian cancer.
Crucially for launch-readiness and pipeline planning, the FDA approved the application 3.5 months ahead of the July 11, 2026 PDUFA goal date. Efficacy is supported by the phase 3 ROSELLA trial (NCT05257408, 381 patients), which demonstrated median progression-free survival (PFS) of 6.5 months versus 5.5 months (hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.54 to 0.91, p = 0.0076) and median overall survival (OS) of 16.0 months versus 11.9 months (HR 0.65, 95% CI 0.51 to 0.83, p = 0.0004) against nab-paclitaxel alone.
Lifyorli is administered at a recommended dosage of 150 mg orally once daily on the day before, the day of, and the day after each nab-paclitaxel infusion (80 mg/m² intravenously on days 1, 8, and 15 of each 28-day cycle) until disease progression or unacceptable toxicity. The drug features no biomarker diagnostic requirements but carries a strict contraindication in patients who require corticosteroids for a lifesaving indication. The wholesale acquisition cost (WAC) has been established at approximately $37,900 per 28-day cycle (nine treatment doses). Cigna has already published an oncology prior-authorization policy (cnf_985) for the agent, and Onco360 has been selected as the national specialty pharmacy partner distributing it.
What is relacorilant (Lifyorli) and why is its selective GR antagonist mechanism new for ovarian cancer?
Glucocorticoid receptors (GR) are widely expressed in epithelial ovarian cancer and other solid tumors. When activated by cortisol—the body's primary stress hormone—these receptors trigger transcriptional programs that promote cell survival, reduce apoptosis, and inhibit the cytotoxic effects of chemotherapy. Historically, standard oncology regimens have co-prescribed synthetic glucocorticoids (such as dexamethasone) to prevent hypersensitivity reactions and chemotherapy-induced nausea. However, these exogenous steroids inadvertently bind to and activate GR, promoting tumor cell survival and contributing to chemoresistance, particularly against taxanes.
Relacorilant is a first-in-class, selective glucocorticoid receptor antagonist. By binding to GR with high affinity, relacorilant blocks cortisol and synthetic corticosteroids from activating the receptor. This blockade prevents the activation of anti-apoptotic pathways and genes, thereby restoring the sensitivity of cancer cells to the cytotoxic action of paclitaxel or nab-paclitaxel.
Unlike older, non-selective cortisol blockers such as mifepristone, relacorilant is highly selective for the glucocorticoid receptor. It does not bind to the progesterone receptor (PR) or estrogen receptor (ER), avoiding progesterone-receptor-related side effects such as endometrial hyperplasia, vaginal bleeding, and abortifacient activity. Commercially, this selective profile positions Lifyorli as a targeted oncology agent rather than an endocrine modifier with multi-receptor off-target toxicities. It is the first selective GR antagonist to enter the oncology therapeutic space, establishing a precedent for target classes addressing microenvironmental resistance.
What did the March 25, 2026 FDA approval add, and why was it 3.5 months early?
The FDA approved Lifyorli in combination with nab-paclitaxel on March 25, 2026. This approval represents a major milestone for Corcept Therapeutics, which has spent years developing GR antagonists. Corcept submitted the new drug application (NDA) in July 2025, and the FDA accepted it for review in September 2025. Because of the strength of the clinical trial data and the clear unmet need in platinum-resistant epithelial ovarian cancer, the FDA approved the application about 3.5 months ahead of its scheduled July 11, 2026 PDUFA goal date.
For market access and pharmacy benefit managers (PBMs), this accelerated timeline compresses the typical pre-launch preparation window. P&T committees that typically rely on the PDUFA date to schedule reviews must adapt to the early launch, illustrating the types of payer barriers in the first 180 days after launch that new-to-market therapies face. This approval has also been incorporated into the broader landscape of the 2026 novel approvals Lifyorli belongs to, highlighting how developers are increasingly leveraging expedited programs to bring specialty oncology agents to market ahead of expectations.
Chronology of the Regulatory Timeline
- Orphan Drug Designation: Relacorilant received orphan drug designation for ovarian cancer, providing clinical trial tax credits and seven years of market exclusivity post-approval.
- Fast Track Status: Granted by the FDA to facilitate the development and expedite the review of drugs to treat serious conditions and fill unmet medical needs.
- NDA Submission: Submitted by Corcept Therapeutics in July 2025 and accepted for FDA review in September 2025, supported by the complete ROSELLA dataset.
- Early Approval: The FDA completed review well ahead of the PDUFA goal date, reflecting the magnitude of the overall survival benefit and the unmet need in platinum-resistant disease.
- Regular (Full) Approval: The FDA granted regular approval on March 25, 2026 on the strength of the statistically significant overall survival benefit demonstrated in the pivotal trial.
What did the ROSELLA trial show for progression-free and overall survival?
The clinical foundation for Lifyorli's approval is the phase 3 ROSELLA trial (NCT05257408). This open-label, randomized, active-controlled trial enrolled 381 patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. Patients were randomized 1:1 to receive either:
- Lifyorli + Nab-Paclitaxel: Relacorilant 150 mg orally once daily on the day before, the day of, and the day after nab-paclitaxel (80 mg/m² IV on days 1, 8, and 15 of a 28-day cycle).
- Nab-Paclitaxel Monotherapy: Nab-paclitaxel 80 mg/m² IV on days 1, 8, and 15 of a 28-day cycle.
The trial achieved its primary endpoint of progression-free survival and its key secondary endpoint of overall survival. The efficacy outcomes are detailed in the table below:
| Endpoint | Lifyorli + Nab-Paclitaxel (N=190) | Nab-Paclitaxel Alone (N=191) | Hazard Ratio (95% CI) | p-value |
|---|---|---|---|---|
| Median Progression-Free Survival (PFS) | 6.5 months | 5.5 months | 0.70 (0.54 to 0.91) | 0.0076 |
| Median Overall Survival (OS) | 16.0 months | 11.9 months | 0.65 (0.51 to 0.83) | 0.0004 |
| **Objective Response Rate (ORR)**¹ | 36.9% | 30.1% | — | — |
¹ PFS and OS are the dual primary endpoints by blinded independent central review (final OS analysis). ORR is a secondary endpoint from the primary (PFS) analysis; the complete-response rate was 3.2% in the combination arm versus 2.1% with nab-paclitaxel alone.
ROSELLA’s demonstration of a 4.1-month overall survival benefit (16.0 vs 11.9 months, HR 0.65) is clinically significant in this patient population. Historically, single-agent chemotherapies (such as pegylated liposomal doxorubicin, paclitaxel, or topotecan) in platinum-resistant disease yield median overall survival of only 9 to 12 months. The combination of relacorilant and nab-paclitaxel represents a meaningful efficacy improvement without introducing the severe cumulative toxicities associated with platinum re-challenge.
Statistical Subgroup Analyses
- Prior Lines of Therapy: Efficacy was maintained across patients who received one, two, or three prior regimens, though the hazard ratio for overall survival was most favorable in patients receiving Lifyorli as their second-line systemic option in the platinum-resistant setting.
- Prior Bevacizumab Exposure: Because the trial required prior bevacizumab use, all enrolled patients had demonstrated resistance or progression on anti-angiogenic therapy. The survival benefit confirms that relacorilant can overcome microenvironmental resistance pathways that develop during anti-VEGF treatment.
Who is eligible: the prior-bevacizumab requirement, line-of-therapy window, and no-biomarker design?
The FDA-approved indication for Lifyorli restricts eligibility to a specific subset of patients with platinum-resistant disease:
- Prior Systemic Regimens: Patients must have received one to three prior systemic regimens. This ensures the drug is positioned in the early-line platinum-resistant setting, typically as second- to fourth-line therapy overall.
- Prior Bevacizumab Requirement: At least one of these prior systemic regimens must have included the anti-VEGF monoclonal antibody bevacizumab (Avastin) or an approved biosimilar. This is a crucial gating mechanism; patients who have not received bevacizumab are not candidates for Lifyorli under the approved label.
- No Biomarker Gating: Unlike many modern targeted oncology agents, Lifyorli does not require a companion diagnostic or biomarker test (such as BRCA mutation, homologous recombination deficiency [HRD], or folate receptor alpha [FRα] expression). This simplifies patient identification but raises questions about how payers will verify clinical appropriateness without a diagnostic report. The contrast between this design and standard oncology prior authorization is discussed further in the context of oncology biomarker documentation in prior authorization.
Safety and Tolerability Gating
Payer prior authorization and clinical pathways must also account for Lifyorli’s safety profile. The most common adverse reactions (incidence ≥20%) observed in ROSELLA were neutropenia, anemia, fatigue, peripheral neuropathy, nausea, diarrhea, and decreased appetite. The labeling contains major warnings and precautions that serve as clinical gates:
- Corticosteroid Contraindication: Lifyorli is contraindicated in patients who require systemic corticosteroids for a lifesaving indication (e.g., severe asthma exacerbations, active autoimmune disease flare, or acute transplant rejection). Because relacorilant is a GR antagonist, it will block the therapeutic effect of these corticosteroids.
- Adrenal Insufficiency: Patients may develop adrenal insufficiency, particularly if they are receiving exogenous corticosteroids or have compromised adrenal function. Prescribers must monitor for signs and symptoms (hypotension, hypoglycemia, hyperkalemia, fatigue) and discontinue Lifyorli if adrenal insufficiency is suspected.
- Neutropenia and Severe Infections: Grade 3 or higher neutropenia occurred in 44% of patients receiving the combination versus 25% with nab-paclitaxel alone in the final ROSELLA safety analysis, reflecting the longer median treatment duration in the combination arm. Absolute neutrophil count (ANC) must be monitored prior to each cycle and during treatment.
Clinical Management and Monitoring Protocols
To ensure patient safety, oncology clinics must implement the following monitoring schedule:
- Hematologic Surveillance: Complete blood counts (CBC) must be obtained on days 1, 8, and 15 of each 28-day cycle. Chemotherapy must be held if the absolute neutrophil count drops below 1,000/mm³ or if platelets drop below 75,000/mm³.
- Adrenal Assessment: Serum cortisol and ACTH levels should be checked at baseline and if patients exhibit signs of adrenal fatigue. If adrenal insufficiency is confirmed, Lifyorli must be discontinued and physiologic hydrocortisone replacement initiated.
- Electrolyte Monitoring: Electrolyte disturbances, including hypokalemia, can occur with the regimen. Potassium and other electrolyte levels should be monitored during treatment and corrected promptly to reduce the risk of cardiac arrhythmias.
What does Lifyorli cost and how is it distributed (WAC, revenue guide, Onco360)?
Corcept Therapeutics has established the wholesale acquisition cost (WAC) for Lifyorli at approximately $37,900 per 28-day cycle, which covers nine treatment doses. This price reflects the specialty oncology category, where novel mechanisms and survival-prolonging agents command premium pricing. Because Lifyorli ships through a single specialty pharmacy rather than retail channels, cash-price aggregators are not a reliable reference point; the WAC is the list-price benchmark payers and 340B entities should model.
Independent analysts at Clarivate, in their Drugs to Watch 2026 review, projected roughly $150 million in G7 sales for Lifyorli by 2031, a comparatively modest figure that reflects the gradual uptake expected as payers establish formulary coverage and clinical pathways adopt the new regimen during the first three to six months post-launch. Separately, Corcept raised its total company 2026 revenue guidance to $950–$1,050 million in its first-quarter results as it scaled launch infrastructure.
To control distribution and monitor adherence, Lifyorli is distributed exclusively through a limited specialty pharmacy network. Onco360 has been selected as the primary specialty pharmacy partner. Onco360 will manage the fulfillment of Lifyorli prescriptions, coordinate patient intake, verify insurance coverage, and facilitate access to patient assistance programs. For access teams, this limited distribution model prevents retail leakage but requires strict coordination between the prescriber, the specialty pharmacy, and the payer to minimize time-to-therapy.
Enrollment and Fulfillment Workflow
- Prescription Intake: The clinical team submits a unified referral form to Onco360 containing patient demographics, clinical notes (confirming prior bevacizumab use and line of therapy), and the prescription for both Lifyorli and nab-paclitaxel.
- Benefit Investigation: Onco360 performs a comprehensive benefit check, verifying whether the claim will be routed through the pharmacy benefit (as an oral specialty drug) or the medical benefit (if integrated into a buy-and-bill chemotherapy plan).
- Prior Authorization Support: Onco360 contacts the payer to initiate the PA process, uploading the required clinical documentation.
- Copay and Foundation Coordination: If the patient faces high cost-sharing (common in Medicare Part D), the specialty pharmacy coordinates with oncology foundations or Corcept's copay card program to reduce the patient's out-of-pocket exposure.
- Dispensing and Delivery: Once authorized, Lifyorli is shipped directly to the patient's home in temperature-controlled packaging, scheduled to arrive before the patient's next scheduled nab-paclitaxel infusion.
How will payers cover it, and what does the Cigna oncology PA policy signal?
As a high-cost specialty oncology agent, Lifyorli will be placed on the specialty tier of commercial and Medicare Part D formularies, almost universally subject to prior authorization (PA) and quantity limits. Payers are expected to align their PA criteria closely with the FDA-approved label and the ROSELLA trial inclusion criteria.
Cigna was one of the first major commercial payers to publish an oncology prior-authorization policy for Lifyorli (Policy cnf_985). This policy signals how the broader payer community will manage the drug:
- Indication Verification: The patient must have a diagnosis of platinum-resistant epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. Resistance is defined as progression within six months of completing a platinum-based chemotherapy regimen.
- Prior Therapy Verification: Documentation must confirm that the patient has received at least one prior systemic therapy regimen that included bevacizumab or a bevacizumab biosimilar. It must also verify that the patient has received no more than three prior systemic regimens in total.
- Combination Therapy: The prescription must be for Lifyorli in combination with nab-paclitaxel, matching the ROSELLA trial protocol. Lifyorli monotherapy will not be approved.
- Prescriber Restriction: The drug must be prescribed by, or in consultation with, a gynecologic oncologist or medical oncologist.
- Exclusion Criteria: Patients requiring chronic systemic corticosteroids (beyond physiologic replacement doses) will be denied coverage due to the drug's mechanism of action.
This policy template represents a standard specialty oncology coverage and prior authorization approach. PBMs will use electronic prior authorization (ePA) portals to confirm these points. Because Lifyorli lacks a companion biomarker, clinical notes confirming prior bevacizumab use and line of therapy will be the primary documentation required to secure approval.
Reauthorization and Continuation Criteria
Payers will require reauthorization every three to six months to monitor for disease progression or toxicity. To secure continued coverage, the provider must document:
- Absence of Disease Progression: Confirmed via RECIST criteria on follow-up CT/MRI scans or stable CA-125 tumor markers.
- Acceptable Tolerability: Absence of Grade 3/4 adrenal insufficiency, severe infection, or unresolved myelosuppression.
- Adherence Verification: Confirmation from the specialty pharmacy that the patient has filled their Lifyorli prescriptions consistently, matching the chemotherapy schedule.
Where does Lifyorli sit in platinum-resistant ovarian cancer pathways versus bevacizumab and PARP inhibitors?
The management of platinum-resistant ovarian cancer has long been a clinical challenge. When a patient progresses within six months of platinum therapy, the disease is considered platinum-resistant, and the prognosis is poor. Established clinical management has historically involved single-agent non-platinum chemotherapy (paclitaxel, nab-paclitaxel, pegylated liposomal doxorubicin [PLD], or topotecan), either alone or in combination with bevacizumab.
The positioning of Lifyorli is shaped by three therapeutic categories:
1. The Bevacizumab-Pretreated Population
Bevacizumab (Avastin) is commonly used in both the first-line maintenance setting and the platinum-sensitive recurrent setting. Under the Lifyorli label, prior bevacizumab is a prerequisite. This places Lifyorli + nab-paclitaxel directly as a subsequent line of therapy for patients who have already progressed on or after bevacizumab. By sensitizing cancer cells to nab-paclitaxel, Lifyorli provides a therapeutic option for patients whose disease has become refractory to standard anti-angiogenic and cytotoxic combinations.
2. PARP Inhibitors (Olaparib, Niraparib, Rucaparib)
PARP inhibitors are established as maintenance therapy for patients with BRCA mutations or HRD-positive tumors who are in response to platinum-based chemotherapy. Once a patient develops platinum-resistant disease, PARP inhibitors are generally no longer effective, and patients are transitioned to systemic chemotherapy. Lifyorli does not compete with PARP inhibitors in the maintenance setting; rather, it represents a treatment option after PARP inhibitor failure and subsequent platinum resistance have occurred. Because Lifyorli has no biomarker requirement, it is available to both HRD-positive and HRD-negative patients, filling a major gap for patients who do not qualify for, or have progressed on, PARP inhibitor therapy.
3. Comparison with Current Standard Regimens
The table below illustrates how the Lifyorli + nab-paclitaxel regimen compares with other common options in the platinum-resistant setting:
| Regimen | Median PFS | Median OS | Key Advantages | Primary Disadvantages / Access Gaps |
|---|---|---|---|---|
| Lifyorli + Nab-Paclitaxel | 6.5 months | 16.0 months | Significant OS benefit (16.0 vs 11.9 mo); oral GR antagonist mechanism restores taxane sensitivity. | High cost ($37,900/cycle); corticosteroid contraindication; prior bevacizumab required. |
| Single-Agent Chemotherapy (e.g., PLD, Topotecan) | 3.5 – 4.0 months | 9.0 – 12.0 months | Low cost; widely available; generic options; familiar safety profile. | Limited efficacy; rapid progression; cumulative myelosuppression and alopecia. |
| Chemotherapy + Bevacizumab | 6.0 – 6.8 months | 13.0 – 14.5 months | Established efficacy; dual mechanism (cytotoxic + anti-angiogenic); generic biosimilars available. | Cumulative hypertension, proteinuria, wound healing complications, bowel perforation risk. |
| Mirvetuximab Soravtansine (Elahere) | 5.6 months | 16.5 months | Target-specific (antibody-drug conjugate) for folate receptor alpha (FRα)-positive disease. | Restricted to FRα-high expressing tumors (~35-40% of patients); requires companion diagnostic. |
Lifyorli + nab-paclitaxel offers overall survival comparable to the antibody-drug conjugate mirvetuximab soravtansine (Elahere) but does so without the need for biomarker screening. This makes Lifyorli a versatile option in the platinum-resistant pathway, provided the patient has received prior bevacizumab.
FAQs
Is Lifyorli (relacorilant) approved for all platinum-resistant ovarian cancer or only after bevacizumab?
Lifyorli is specifically approved for patients who have received one to three prior systemic regimens, at least one of which must have included bevacizumab (or a biosimilar). Payer prior-authorization policies, including Cigna's cnf_985, require documentation of this prior bevacizumab therapy. Patients who are bevacizumab-naive are not eligible under the approved label.
Does relacorilant require a biomarker test before prescribing?
No. Unlike therapies such as PARP inhibitors (which require BRCA or HRD testing) or mirvetuximab soravtansine (which requires FRα-high testing), Lifyorli has no biomarker diagnostic requirement. Any patient with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who meets the prior therapy and clinical criteria is eligible, regardless of mutation status.
Why is Lifyorli contraindicated in patients who need corticosteroids for a lifesaving indication?
Lifyorli is a potent and selective glucocorticoid receptor (GR) antagonist. It works by blocking cortisol and synthetic corticosteroids from binding to and activating the glucocorticoid receptor. If a patient requires systemic corticosteroids for a lifesaving indication (such as severe asthma, acute allergic reactions, or transplant rejection), Lifyorli will block the efficacy of those corticosteroids, putting the patient at risk. Physiologic replacement doses of corticosteroids for adrenal insufficiency may be allowed, but supraphysiologic doses for acute inflammatory states are contraindicated.
Sources
- FDA. FDA approves relacorilant with nab-paclitaxel for platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. U.S. Food and Drug Administration. March 25, 2026. FDA Approval Notification
- Corcept Therapeutics. FDA Approves Corcept's Selective Glucocorticoid Receptor Antagonist Lifyorli (relacorilant) for the Treatment of Platinum-Resistant Ovarian Cancer. Press Release. March 25, 2026. Corcept Press Release
- Lorusso D, et al. Overall survival with relacorilant and nab-paclitaxel in patients with platinum-resistant ovarian cancer (ROSELLA): a phase 3 randomised controlled trial. The Lancet. April 2026. The Lancet ROSELLA
- Reuters. Corcept Therapeutics shares surge as lead drug gets FDA nod for ovarian cancer. March 25, 2026. Reuters Coverage
- Targeted Oncology. NDA for Relacorilant in Platinum-Resistant Ovarian Cancer Submitted to FDA (primary-analysis efficacy including objective response rate). 2025. Targeted Oncology
- Corcept Therapeutics. First Quarter 2026 Financial Results and Corporate Update (2026 revenue guidance). April 30, 2026. Corcept Q1 2026 Results
- Onco360. Onco360 Has Been Selected as the National Pharmacy Partner for Lifyorli (relacorilant). March 25, 2026. Onco360 Announcement
- Cigna. Oncology Prior Authorization Coverage Position Criteria: Lifyorli (relacorilant) Policy cnf_985. Cigna Coverage Policies. 2026. Cigna Policy cnf_985
- DailyMed. Lifyorli (relacorilant) tablets, for oral use. Highlights of Prescribing Information. National Institutes of Health / National Library of Medicine. March 2026. DailyMed Prescribing Information
- FiercePharma. Corcept's lead drug bounces back from FDA snub to first approval with Lifyorli in ovarian cancer. March 2026. FiercePharma Coverage
- BioWorld. Early FDA wins: Corcept's Lifyorli, Denali's Avlayah. March 2026. BioWorld Article
