Corcept Therapeutics Picks Up Speed New Clinical Trials Ahead

Corcept Therapeutics Picks Up Speed New Clinical Trials Ahead

130 Patients -Open-label dose titration, then responders enter randomized withdrawal – Relacorilant vs. Placebo Oct/Nov 2018 130 Patients – Relacorilant vs. Placebo 1H-2020* CORT118335 CEO Belanoff stated that CORT118335 produced promising results in animal models of fatty liver disease including a reduction of white fat in the liver and other organs. Additional work with metabolic syndrome is being conducted by independent investigators. Cushing’s syndrome patients, especially those with mild disease, are “human models” for metabolic syndrome. Corcept’s patent for treating fatty liver disease is now published in the US and Europe. Why CORT118335 rather than Korlym? Cushing’s syndrome requires a drug that has wide dispersion through the body (Korlym). On the other hand, metabolic syndrome, especially involving NASH disease, requires a drug that is well absorbed by the liver (CORT118335). CORT118335’s targeting is inappropriate for Cushing’s syndrome. About two years ago, we also underscored CORT118335’s potential use for treating alcohol withdrawal in animal models . Metabolic Syndrome In the Phase 1 trial, it is a 3-part, single center study of single and multiple ascending doses in healthy subjects. Quotient Clinical in the UK is conducting the trial, the same group that executed the Phase 1 for relacorilant. Part 1 of the study is a double-blind, randomized, placebo-controlled assessment of single-ascending doses (SAD) of CORT118335. Subjects will be enrolled sequentially into 1 of up 7 cohorts (Cohorts A to G), each containing 8 subjects. Within each cohort, 6 subjects will be randomly assigned to receive a single dose of CORT118335 and 2 subjects will be randomly assigned to receive a single dose of matching placebo. Part 2 Cohort A , food-effect, will be an open-label 2-way crossover study in one cohort of 12 subjects, randomized in a 1:1 ratio to receive a single dose of CORT118335 once after an overnight fast and once after a high-fat breakfast or the alternate sequence, over 2 study periods separated by a washout of at least 7 days/5 half-lives. Part 2 Cohort B , PD cohort, will be a double-blind, randomized, placebo-controlled, 3-way cross-over study and will serve as proof of pharmacological effect (GR modulation) for CORT118335. Subjects will be randomized in a 1:1:1 ratio to receive placebo, and two dose levels of CORT118335 in one of three treatment sequences across 3 study periods separated by washouts of at least 7 days/5 half-lives. On each occasion, the ability of CORT118335 to ameliorate the pharmacological effects of a single dose of prednisone will be measured . Part 3 is a double-blind, randomized, placebo-controlled assessment of multiple oral ascending doses of CORT118335. Subjects will be enrolled sequentially into 1 of up to 4 cohorts (Cohorts A to D), each containing 12 subjects. Within each cohort, 9 subjects will be randomly assigned to receive CORT118335 and 3 subjects to receive matching placebo daily for 14 days. There is an option for the last cohort (Cohort D) to undergo prednisone challenge before and after treatment with CORT118335 or placebo to study the effects of CORT118335 on the response to prednisone challenge. Phase 1 Results – 136 Healthy Patients – Dose Ranging, Double-Blind CORT118335 ± Prednisone, Glucose, Placebo Phase 2 Launch – Antipsychotic Weight Gain Mitigation CORT118335 Phase 2 Launch – NASH Treatment CORT118335 Cancer Program Cortisol modulation may play a role in treating solid tumors through two mechanisms. First , in cancers where the tumors express GR, such as pancreatic, triple negative breast, and ovarian cancer. cortisol stimulates genes that retard apoptosis – the programmed suicide of dysfunctional cells. Chemotherapies aim to provoke apoptosis. Cortisol modulators should reverse this effect and downregulate the “apoptosis suppressing genes”. This enables chemotherapy to make a stronger impact . Second , cortisol modulation may help the immune system fight cancer . A healthy body regularly produces cancer cells, but the immune system identifies and destroys them. Even at normal levels, cortisol suppresses the immune system. Unfortunately, the stress of cancer and its treatment raise cortisol activity above normal levels and creates even greater immunosuppression. Cortisol modulators counter this effect by mitigating cortisol’s effects, thus freeing the immune system to act more potently. Corcept’s oncology program builds on preclinical and clinical research at the University of Chicago and confirmed by researchers at Sloan Kettering . There is great interest in therapies that stimulate the immune system to fight cancer because it can be a powerful weapon. Solid Tumors CORT125134 ( relacorilant ) is in a Phase I/II trial to treat solid tumors including breast and ovarian cancer. In the Phase I part, CORT125134 is paired with Abraxane. Dose cohorts are employed to seek the maximum tolerated dose (MTD). Corcept expects to open additional expansion cohorts in patients with other tumor types, most likely ovarian and triple-negative breast cancer in 2018. Corcept is opening a cohort of pancreatic cancer patients. Given the preclinical animal results, we aren’t surprised. Relacorilant has shown potential. Besides lacking a couple side effects associated with Korlym, the animal models and early clinical data for treating solid tumors looks good, especially for pancreatic and ovarian cancers. Relacorilant appears to perform better than Korlym in mouse models of TNBC and castration-resistant prostate cancer. It also demonstrated good results with ovarian cancer cells in the lab. It is like Korlym but lacks some of its side effects. Relacorilant is already being paired with a checkpoint inhibitor , namely Pembrolizumab ( Keytruda ). Ongoing Results –Relacorilant (100 mg/ daily) + Abraxane (80 mg/m 2 ) 20 Patients with Pancreatic Cancer Q4-2018 Phase II Results – Expansion Cohorts – (~24 pts per Cohort) Relacorilant + Abraxane (ovarian & triple-negative breast cancer)

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