Lifyorli

Lifyorli (relacorilant) is a prescription cancer medicine to treat platinum-resistant epithelial ovarian, fallopian tube, and primary peritoneal cancer in certain adults. It is used in combination with nab-paclitaxel (Abraxane) chemotherapy in patients who have already received 1 to 3 prior systemic treatment regimens, including at least one regimen containing bevacizumab.

Lifyorli is a glucocorticoid receptor antagonist (GRA). Lifyorli works by blocking the glucocorticoid receptor, a pathway linked to cortisol signaling, which may help make Abraxane chemotherapy more effective in hard-to-treat ovarian cancers.

Lifyorli capsules are taken the day before, the day of, and the day after each nab-paclitaxel infusion. The recommended Lifyorli dose is 150 mg orally once daily on those treatment days. Take Lifyorli with food and swallow capsules whole. Do not crush, chew, dissolve, or split the capsules.

In the phase 3 ROSELLA trial (NCT05257408), patients treated with Lifyorli plus nab-paclitaxel had a 35% reduction in the risk of death compared with nab-paclitaxel alone, with a median overall survival of 16.0 months versus 11.9 months.

• Neutropenia and severe infections can occur. Complete blood counts should be monitored before each weekly treatment and as clinically indicated. Treatment may be withheld, dose reduced, or Liyorli permanently discontinued, depending on severity.
• Adrenal insufficiency can occur and may be life-threatening. Serum cortisol levels do not provide an accurate assessment of adrenal insufficiency in patients receiving LIFYORLI.
• Because Lifyorli blocks the glucocorticoid receptor, it may worsen conditions treated with systemic glucocorticoids and may make glucocorticoids less effective.
• This medicine can cause fetal harm. Verify pregnancy status before starting treatment and advise effective contraception during treatment and for 1 week after the last dose.
• Lactation: Advise not to breastfeed.
• Hepatic Impairment: Avoid use in patients with moderate or severe hepatic impairment.

Important: Lifyorli should not be taken in patients receiving concurrent systemic glucocorticoid therapy for lifesaving purposes, as Lifyorli can make glucocorticoid medicines less effective.

The most common Lifyorli side effects were tiredness, nausea, diarrhea, rash, decreased appetite, and changes in laboratory tests, including decreased hemoglobin, decreased neutrophils, and decreased platelets. These common side effects occurred in 20% or more of patients receiving Lifylori in combination with nab-paclitaxel in the phase 3 ROSELLA trial.

Serious side effects

Get emergency medical help if you have signs of an allergic reaction: hives, difficult breathing, swelling of your face, lips, tongue, or throat.

Lifyorli may cause serious side effects. Call your doctor at once if you have:

• low adrenal hormone levels - nausea, vomiting, stomach pain, loss of appetite, feeling tired or light-headed, muscle or joint pain, skin discoloration, craving salty foods; or
• low blood cell counts - fever, chills, tiredness, mouth sores, skin sores, easy bruising, unusual bleeding, pale skin, cold hands and feet, feeling light-headed or short of breath.

Serious adverse reactions occurred in 35% of patients taking Lifyorli in combination with nab-paclitaxelin. Serious adverse reactions reported in at least 2% of patients included neutropenia, pneumonia, pleural effusion, febrile neutropenia, and fatigue.

Permanent discontinuation due to adverse reactions occurred in 9% of patients. The adverse reaction leading to permanent discontinuation in more than 2% of patients was intestinal obstruction.

This is not a complete list of side effects, and others may occur. Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088

You should not use this medicine if you are allergic to the the active ingredient relacorilant or inactive ingredients, or if you:

• need steroid medicines taken by mouth or given by injection for a life-threatening condition such as after an organ transplant or to treat an autoimmune disease.

Before you take this medicine, tell your healthcare provider about all your medical conditions, including if you:

• plan to have surgery or have had surgery within the past 30 days
• have liver problems

Pregnancy

Tell your healthcare providers if you are pregnant or plan to become pregnant, as Lifyorli can harm an unborn baby if the mother or the father is using this medicine.

Females who are able to become pregnant:

• Your healthcare provider should do a pregnancy test before you start treatment with this medicine.
• Use effective birth control (contraception) during treatment with Lifyorli and for 1 week after your last dose. Talk with your healthcare provider about birth control methods you can use during this time.
• Tell your healthcare provider right away if you become pregnant or think you are pregnant during treatment with this medicine.

Males with female partners who are able to become pregnant:

• Use effective birth control (contraception) during treatment with Lifyorli and for 1 week after your last dose.

Breastfeeding

Tell your healthcare providers if you are breastfeeding or plan to breastfeed, as it is not known if Lifyorli passes into your breast milk.

• Do not breastfeed during treatment with this medicine and for 1 week after your last dose.

Follow the dosing instructions provided by your healthcare professional

The recommended dose of Lifylorli is 150 mg orally once on the day before, the day of, and the day after each nab-paclitaxel infusion, until disease progression or unacceptable toxicity. Lifyorli dose may be reduced or stopped due to side effects.

Take Lifyorli with food and swallow capsules whole. Do not crush, chew, dissolve, or split the capsules.

If a dose is missed by less than 12 hours, take the missed dose. If a dose is missed by 12 hours or more, skip the missed dose and take the next dose at the regularly scheduled time. If vomiting occurs after taking a dose, do not take an additional dose.

The recommended nab-paclitaxel dose when used with Lifyorli is 80 mg/m² by intravenous infusion on Days 1, 8, and 15 of each 28-day cycle. Dosage modifications may be required due to side effects. Do not substitute other paclitaxel formulations for nab-paclitaxel in this regimen.

Lifylori is supplied as 25 mg and 100 mg soft gelatin capsules.

The 25 mg capsule is opaque, dark brown, and oval with “CR25” printed in black. The 100 mg capsule is opaque yellow and oblong with “CR100” printed in black.

Tell your healthcare provider about all medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal products.

Both relacorilant and paclitaxel are CYP3A substrates, and strong CYP3A inducers can reduce exposure and potentially reduce effectiveness.

• Strong CYP3A Inducers: Avoid coadministration of Lifyorli plus nab-paclitaxel with strong CYP3A inducers. Both relacorilant and paclitaxel are CYP3A substrates. Coadministration of strong CYP3A inducers can decrease concentrations of relacorilant and paclitaxel, which may reduce their effectiveness.
• CYP2C8 and Moderate CYP3A Inducers: Monitor for reduced effectiveness of Lifyorli plus nab-paclitaxel with CYP2C8 inducers and moderate CYP3A inducers. Paclitaxel is a substrate of CYP2C8 and CYP3A, and relacorilant is a CYP3A substrate. Coadministration of CYP2C8 and moderate CYP3A inducers can decrease concentrations of paclitaxel and relacorilant, which may reduce their effectiveness.
• CYP2C8 Inhibitors: Monitor for increased adverse reactions and modify the dosage for adverse reactions as recommended. Paclitaxel is a substrate of CYP2C8. Coadministration of CYP2C8 inhibitors may increase concentrations of paclitaxel, which may increase the risk of adverse reactions.
• CYP3A Substrates: Avoid concomitant use unless otherwise recommended in the Prescribing Information for CYP3A substrates. Relacorilant is a strong CYP3A inhibitor. Relacorilant increases exposure of CYP3A substrates, which may increase the risk for adverse reactions related to these substrates.
• Certain CYP2C8 Substrates: Avoid concomitant use unless otherwise recommended in the Prescribing Information for CYP2C8 substrates, where minimal concentration changes may lead to reduced effectiveness. Relacorilant is a weak CYP2C8 inducer. Relacorilant decreases the exposure of CYP2C8 substrates, which may decrease the effectiveness related to these substrates.

Other drugs may interact with Lifyorli; not all possible drug interactions are listed here.

• Store at room temperature at 68°F to 77°F (20°C to 25°C).
• Store in the original carton.

Manufactured for Corcept Therapeutics Incorporated, Redwood City, CA 94065

Active ingredient: relacorilant

Inactive ingredients: butylated hydroxytoluene, lauroyl polyoxyl-32 glycerides, and propylene glycol caprylate.

The 25mg capsule shell contains: black iron oxide, gelatin, red iron oxide, sorbitol special glycerin blend, titanium dioxide, and yellow iron oxide.

The 100 mg capsule shell contains: gelatin, sorbitol special glycerin blend, titanium dioxide, and yellow iron oxide.

The printing ink contains: ammonium hydroxide, black iron oxide, ethanol, ethyl acetate, isopropyl alcohol, macrogol/polyethylene glycol, polyvinyl acetate phthalate, propylene glycol, and purified water.