Corcept Therapeutics Incorporated

Joseph Custodio

Hazel Joan Hunt

Stacie Shepherd

Andrew Greenstein

Grace Mann

Iulia Cristina Tudor

William Guyer

Lawrence Lu

Methods for treating a cancer patient with a neutrophil-to-lymphocyte ratio (NLR) greater than 3 are disclosed, comprising administering a nonsteroidal glucocorticoid receptor antagonist (GRA) to such a cancer patient, effective to reduce the patient's NLR. The methods include administering a nonsteroidal GRA and a cancer treatment to such a cancer patient, effective to reduce the patient's NLR and enhance the treatment of the cancer patient. The GRA may be orally administered. The nonsteroidal GRA may be a nonsteroidal compound comprising a heteroaryl ketone fused azadecalin structure (e.g., relacorilant) or an octahydro fused azadecalin structure (e.g., exicorilant). The cancer treatment may include chemotherapy, immunotherapy, radiation therapy, administration of an anti-angiogenic agent, administration of a growth factor inhibitor, and surgery. The methods may enhance the cancer treatment, improve the prognosis of the cancer patient, improve the survival of the cancer patient, and provide beneficial clinical effects and advantages to the patient.

Method of normalizing the neutrophil to lymphocyte ratio in cancer patients with a selective glucocorticoid receptor antagonist

Applicant discloses methods and compositions for treating a patient suffering from amyotrophic lateral sclerosis (ALS) comprising administration of a heteroaryl ketone fused azadecalin compound. In embodiments, the heteroaryl ketone fused azadecalin compound is dazucorilant: (R)-(1-(4-fluorophenyl)-6-((4-(trifluoromethyl)phenyl) sulfonyl)-4, 4a, 5,6,7,8-hexahydro-1-H-pyrazolo[3,4-g]isoquinolin-4a-yl) (pyridin-2-yl)methanone, having the chemical structure illustrated as Suitable doses include daily administration of 150 milligrams and 300 milligrams of dazucorilant. Suitable doses include daily administration of dazucorilant with food, or with water, or with food and water. Daily administration of dazucorilant is effective to increase dazucorilant exposure up to about 2-fold when continued for seven days or more. Administration of such a heteroaryl ketone fused azadecalin compound may comprise oral administration, enteral administration, or other administration. Pharmaceutical compositions comprising dazucorilant are useful in the treatment of patients suffering from ALS. Suitable pharmaceutical compositions comprising dazucorilant include, e.g., pharmaceutical compositions for oral administration and pharmaceutical compositions for enteral administration.

Treatments for amyotrophic lateral sclerosis using dazucorilant

Many drugs useful in treating cancer are metabolized by CYP2C8 enzymes, by CYP3A4 enzymes, or both. The effects of concomitant administration of relacorilant and paclitaxel, a drug used to treat cancer that is a substrate for both CYP2C8 and CYP3A4, are disclosed herein. Relacorilant potently inhibited CYP2C8 and CYP3A4 in in vitro tests, indicating that co-administration of relacorilant and paclitaxel would increase paclitaxel plasma exposure more than 5-fold in vivo, requiring significant reductions in paclitaxel doses when co-administering paclitaxel with relacorilant. Surprisingly, paclitaxel plasma exposure increased only by about 80% instead of the expected more than 5-fold increase expected with concomitant relacorilant and paclitaxel administration. Applicant discloses safe methods of co-administering relacorilant and paclitaxel by reducing the dose of paclitaxel to about half the paclitaxel dose used when paclitaxel is administered alone. Relacorilant and such reduced doses of paclitaxel may be co-administered to treat cancer, e.g., ovarian or pancreatic cancer.

Concomitant administration of glucocorticoid receptor modulator relacorilant and paclitaxel, a dual substrate of CYP2C8 and CYP3A4

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Menlo Park, CA, United States of America

Joseph Custodio