Corcept Therapeutics Incorporated

Leland Stanford Junior University

Joseph K Belanoff

Hazel Joan Hunt

Alan F Schatzberg

Andreas G Moraitis

Coleman Gross

Onno C Meijer

José Van Den Heuvel

Pejman Cohan

John Francis Unitt

Stacie Shepherd

Ada Lee

Jose Van Den Heuvel

Hazel Hunt

The present invention provides treatment of fatty liver disease using a class of pyrimidinedione cyclohexyl compounds.

Fatty liver disease treatment using glucocorticoid and mineralocorticoid receptor antagonists

Methods and compositions for treating cancer (e.g., ovarian, fallopian tube, uterine, cervical, vaginal, vulvar, or peritoneal cancer) are disclosed. The methods include intermittent administration of a glucocorticoid receptor modulator (GRM), such as a non-steroidal GRM (e.g., relacorilant), which may be orally administered, along with a cancer chemotherapy agent (such as, e.g., bevacizumab) to the patient. The GRM may be administered: at intervals separated by at least one day without GRM administration; by a schedule linked to the cancer chemotherapy schedule (e.g., a weekly chemotherapy regimen); on the day of, or the day before, or the day after, chemotherapy administration; by combinations thereof; and/or on other days. Ovarian cancer patients receiving intermittent relacorilant administration along with nab-paclitaxel administration had improved overall survival, improved progression free survival, improved duration of response, and other benefits as compared to patients not receiving relacorilant while receiving nab-paclitaxel.

Intermittent dosing of glucocorticoid receptor modulators for the treatment of ovarian and other cancers

Applicant provides methods of treating diseases including Cushing's syndrome and hormone-sensitive cancers by concomitant administration of a glucocorticoid receptor modulator (GRM) and steroidogenesis inhibitors, and by concomitant administration of a GRM and CYP3A inhibitors. The GRM may be, e.g., mifepristone; the CYP3A inhibitors or steroidogenesis inhibitors (collectively 'inhibitors') may be, e.g., ketoconazole or itraconazole. Inhibitors may cause toxicity or other serious adverse reactions; concomitant administration of inhibitors with other drugs may increase the risk of such toxicity and adverse reactions due to the inhibitors and/or the other drugs. Applicant has surprisingly found that GRMs may be administered to subjects receiving inhibitors without increasing the risk of adverse reactions; for example, Applicant has found that mifepristone may be concomitantly administered with ketoconazole or itraconazole, providing safe concomitant administration of the GRM and ketoconazole or itraconazole. In embodiments, the GRM dose may be reduced during concomitant administration of the GRM with inhibitors.

Concomitant administration of glucocorticoid receptor modulators and CYP3A inhibitors

Methods of Treating Antipsychotic-Induced Weight Gain with Miricorilant Methods and compositions for treating a subject at risk of, or suffering from antipsychotic-induced weight gain are disclosed. The methods include administration of a cyclohexyl pyrimidine glucocorticoid receptor modulator (GRM) such as miricorilant (CORT118335) to a patient receiving, or who has received, or who is expected to receive, an antipsychotic drug such as olanzapine, risperidone, clozapine, or other weight-inducing antipsychotic medication. The GRM (e.g., miricorilant) may be orally administered. Administration of such a GRM along with antipsychotic medication may reduce the amount of weight, or reduce the rate of weight gain, or prevent weight gain, otherwise due to antipsychotic medication alone. The methods may reverse weight gain in a patient previously administered antipsychotic medication. Administration of such a GRM with antipsychotic medication may reduce, or reduce gain in, or prevent gain in, or reverse gain in, insulin resistance or blood levels of liver enzymes (AST, ALT), triglycerides, or insulin.

Methods of treating antipsychotic-induced weight gain with miricorilant

This invention provides for a method of treating secondary adrenal insufficiency by co-administrating therapeutically effective amounts of a glucocorticoid and a glucocorticoid receptor antagonist to the patient in need thereof. In some embodiments, the method includes the proviso that the patient not be otherwise in need of treatment with a glucocorticoid and a glucocorticoid receptor antagonist. The treatment method can increase the patient's morning or basal cortisol level to at least about 12 μg/dL or a standard control level, and in turn, expedite significantly the recovery of the HPA axis. The method provided herein can improve health outcomes and life-threatening complications associated with secondary adrenal insufficiency.

Use of glucocorticoid receptor antagonists in combination with glucocorticoids to treat adrenal insufficiency

Methods are provided for assessing a clinical response to a glucocorticoid receptor antagonist (GRA) in a human subject and for diagnosing Cushing's syndrome.

Methods for treating Cushing's syndrome

This invention provides for a method of treating secondary adrenal insufficiency by co-administrating therapeutically effective amounts of a glucocorticoid and a glucocorticoid receptor antagonist to the patient in need thereof. In some embodiments, the method includes the proviso that the patient not be otherwise in need of treatment with a glucocorticoid and a glucocorticoid receptor antagonist. The treatment method can increase the patient's morning or basal cortisol level to at least about 12 &#x3bc;g/dL or a standard control level, and in turn, expedite significantly the recovery of the HPA axis. The method provided herein can improve health outcomes and life-threatening complications associated with secondary adrenal insufficiency.

The present invention provides a method for optimizing levels of mifepristone in a patient suffering from Cushing's syndrome. The method comprises the steps of treating the patient with seven or more daily doses of mifepristone over a period of seven or more days; testing the serum levels of the patient to determine whether the blood levels of mifepristone are greater than 1631 ng/mL; and adjusting the daily dose of the patient to achieve mifepristone blood levels greater than 1631 ng/mL.

Optimizing mifepristone levels for Cushing's patients

The present invention resides in the discovery that glucocorticoid receptor antagonists are effective for treating muscular dystrophy including type 1 or type 2 myotonic dystrophy. Treatment methods and kits are provided.

Treatment of muscular dystrophy

Applicant provides methods of treating diseases including Cushing's syndrome and hormone-sensitive cancers by concomitant administration of a glucocorticoid receptor antagonist (GRA) and steroidogenesis inhibitors, and by concomitant administration of a GRA and CYP3A inhibitors. Applicant provides methods of treating diseases including Cushing's syndrome and hormone-sensitive cancers by concomitant administration of mifepristone and ketoconazole. Subjects treated with CYP3A inhibitors or steroidogenesis inhibitors may suffer from toxicity or other serious adverse reactions; concomitant administration of other drugs would be expected to increase the risk of such toxicity and adverse reactions. Applicant has surprisingly found that GRAs may be administered to subjects receiving CYP3A inhibitors or steroidogenesis inhibitors such as ketoconazole without increasing risk adverse reactions; for example, Applicant has found that mifepristone may be concomitantly administered with ketoconazole (a CYP3A inhibitor and a steroidogenesis inhibitor), providing safe concomitant administration of the GRA and ketoconazole. In embodiments, the GRA dose may be reduced.

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Menlo Park, CA, United States of America

Joseph K Belanoff