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Corcept Therapeutics - Q3-2019 Highlights - Clinical Results

07:27 EST 8 Nov 2019 | Biotech Watcher


On Thursday, November 7, 2019, Corcept Therapeutics (CORT) reportedQ3-2019 results and held a conference call.

Brief Introduction


Corcept Therapeutics (NASDAQ: CORT) is a profitable, Menlo Park, CA biopharmaceutical company has a vast platform of drugs to impact the glucocorticoid receptor (GR) system. The GR receptors are present in cells throughout the body, and are stimulated by cortisol. Cortisol is commonly known as the “stress hormone”.

The GR system or the “stress system” is pervasive and has wide ranging effects on metabolic processes (i.e. cardiovascular, sugar and insulin usage), mental state, and the immune system. It helps the body meet the demands of special stress.

Corcept is directly sponsoring two programs in human testing: 1) Metabolic syndrome disorders; and 2) Cancer. This is supplemented by an extensive network of university-based investigators, carrying out early-stage clinical trials and animal experiments. There are perhaps no other biotechs that makes such heavy use of independent investigators.

Recent Updates



Highlights


First, the Q3-2019 Korlym sales of $81.5M may be viewed as better than (we) expected. The underlying Q3 growth is propelled by increased scripts. This created net income of $26.3M. The management raised earlier 2019 sales guidance of $285M - $315M to $300M - $315M. Cash increased about $40M.

Second, management announced the approximate milestones for the GRACE pivotal trialfor treating Cushing’s syndrome. The results will arrive in 2021 and the company expects to submit an NDA in Q4-2021.

Third, CEO Joseph Belanoff also gave further details on a Phase 3 in less severe Cushing’s (LSC). It will be a double-blind, placebo-controlled trial of 130 patients in the USA and Europe. We expect this study to enroll and complete faster than the GRACE pivotal study.

Fourth, Corcept released results from the first half of the Phase 2 trial of miricorilant to mitigate antipsychotic induced weight gain (AIWG). After 14 days of treatment, the low dose miricorilant cohort gained significantly less weight and had lower indications of liver toxicity than placebo. Although we’re unsure whether the investor community will agree with us, but this is the most significant item.

Financial Summary



(in Thousands except Share Price & Market Cap)


Q3-2019
Q2-2019
Q1-2019
Q4-2018
Q3-2018
Net Product Sales
$81,505
$72,257
$64,829
$66,831
$64,445
Cost of Sales
1,451
1,377
1,240
1,579
1,308
R&D Expense
22,805
21,656
20,244
18,794
18,860
SG&A Expenses
24,245
24,591
24,389
21,560
21,308
Total Operating Expenses
48,501
47,624
45,873
41,933
41,476
Net Income (Loss) from Operations
33,004
24,633
18,956
24,898
22,969
Net Income (Loss)
26,340
20,186
18,274
22,008
17,747
Total Comprehensive Income
26,333
20,413
18,438
22,015
17,797
Basic & diluted income (loss) per share
0.23
0.22
0.18
0.17
0.16
0.15
0.19
0.18
0.15
0.14
Avg. Shares Outstanding
Basic & Diluted
113,875
121,762
114,340
121,783
114,844
123,895
115,191
125,152
115,798
126,159
Recent Price (per share)
14.60
(11/7/19)
12.23
(8/1/19)
12.23
(5/9/19)
11.49
(2/25/19)
12.23
(11/1/18)
Market Capitalization
1.6B
1.4B
1.4B
1.3B
1.4B
Cash
44,948
58,141
49,650
41,625
33,894
Short-term Marketable Securities
186,697
143,396
137,255
165,135
161,300
Long-term Marketable Securities
35,250
24,165
28,842
-
1,481


First, Better than Expected Sales Revenues



Korlym - Net Sales
Q3-2019
Q2-2019
Q1-2019
Q4-2018
Q3-2018
2018
Total
2019
Total
FY-2019
Guidance
$81.5M
$72.3M
$64.8M
$66.8M
$64.4M
251.2M
$218.6M
$300M-$315M

There was a robust sales increase from Q2 to Q3-2019. We formerly believed that total FY-2019 sales would total ~$290M, but the Q3-2019 sales is bigger than expected.

Management thus raised the bottom end of earlier guidance to net sales of $300M to $315M for FY2019. Corcept expects the sales growth to continue for at least the next couple years. On August 1, it also increased Korlym’s price by a bit less than 8%.

Sales Force Expansion


In response to a question, CEO Belanoff confirmed that the sales force was being enlarged but this won’t impact sales until Q3-2020. This dovetails with our own published estimate:

The sales force is thus increasing from 41 clinical specialists to 55.We think this will take 3 to 4 quarters for this expansion to accrete into significant earnings growth; this translates to Q2-2020 or Q3-2020 sales. (From Biowatch’s Q2-2019 Commentary)


Second, The Cushing’s Program Timeline


Cushing’sis caused by overproduction of cortisol by the adrenal cortex and often involving obesity and high blood pressure. There are an array of physical and mental symptoms including: obesity and diabetes; fatigue and weakness; severe depression and in some instances, psychoses; high blood pressure, and bone loss. It can be fatal.

Corcept plans to add 13 more active recruiting sites by year end for its GRACE pivotal trial.[1]The company expects to submit an NDA in Q4-2021. This FDA submission will be mainly based upon the GRACE results.

If approved, we expect Corcept to aggressively market relacorilant to displace Korlym. Relacorilant has a (much) superior side effect profile, and furthermore its distribution costs should be far lower than Korlym. If Corcept wishes, it can aggressively price relacorilant below Korlym without significantly harming profits. Relacorilant will be preferred over Korlym by physicians and insurances.

This creates a difficult situation for Teva and other providers of generic Korlym. They will be fighting over a limited market.

Third, the Less Severe Cushing’s Trial Launch is Scheduled


A phase 3 trial, focused on Adrenal Adenoma AKA “less severe Cushing’s (LSC), will be launched in Q1-2020. We expect this trial to take less time than the GRACE trial.

We estimate that the LSC patients outnumber the traditional Cushing’s. As diagnostic scans get better, faster, and cheaper, smaller tumors are being detected. These “less severe cases” appears to exacerbate significant numbers of diabetic, obese, and hypertensive patients, especially among the elderly.

If relacorilant is approved in Europe and the USA, we estimate its peak annual revenues to exceed $1B. Why? Physicians who practice in conservative areas of the USA avoid social stigma by not prescribing Korlym. Relacorilant will not suffer from this problem. Furthermore, relacorilant’s superior side effect profile, plus its deployment into LSC should double the market size.

Fourth, Positive Miricorilant Results for AIWG Prevention

























The company also reported data involving 66 healthy patients receiving olanzapine, an antipsychotic that produces serious weight gain. Half the patients were given a low dose (600 mg) of miricorilant. Apparently the miricorilant absorption is very low, and so the achieved blood levels were only one-tenth of the target goal, and therefore we are quite pleased with results. It underscores miricorilant’s potency.[1]

We expect better results with the higher dose group (900 mg). Corcept is also currently testing a superior formulation that provides stronger bioavailability, to be used in future clinical trials.    

Market Size


Schizophrenia afflicts about 1% of the worldwide population including 2.5M to 3.2M U.S. residents. About 100,000 U.S. residents will be diagnosed in 2019. There is a common core of debilitating psychotic thinking and cognitive slippage, although the negative symptoms like blunt affect and social indifference are also tragic. Some will display hypervigilant paranoid delusions, while others wither away with catatonic withdrawal.

Antipsychotics are also prescribed to patients with atypical psychosis and mood disorders (e.g. bipolar disorder, psychotic depression) that feature psychosis and bizarre thinking. Lastly, it may be prescribed to patients with severe personality disorders.  In 2013, nearly 1.6% of U.S. adults filled a prescription for antipsychotics. Not all were chronic users, but it still reflects a large number.

Problem Severity


Atypical antipsychotics - like olanzapine, quetiapine, and risperidone- are usually the first-line agents for treating schizophrenia. However, there’s a vicious set of side effects. The atypical antipsychotics induce weight gain and increased risk of Type 2 diabetes.

Schizophrenics treated with Atypical Antipsychotics typically die in their mid-50s…and metabolic syndrome complications are a main contributing factor. Popularly prescribed antipsychotics cause significant metabolic disintegration. 

The FDA is very interested. Why? Because this disease arises from our medical treatments. It is a financial and social disaster.

Corcept Clinical Program


The holy grail is clear: the effectiveness of the atypical antipsychotics, without the metabolic disintegration. For dominating the AIWG market, a drug candidate should show consistent efficacy under the following conditions:

1) Weight-gain reversal in recently obese schizophrenics. (Launched)
2) Weight-gain reversalin chronically obese, schizophrenics. (Launch 2021)
3) Weight-gain mitigation with a range of antipsychotics. (Ongoing)

And Corcept is considering:
4) Weight-gain prevention in first- and second-time treated schizophrenics.

No drug has ever achieved this in humans. The best of the best competitor, metformin, fails whenever it’s tested under less than ideal conditions. Its treatment effect is not robust.  Corcept is positioning CORT118335 to dominate this indication.

Hepatotoxicity


While antipsychotics like olanzapine elevate biomarkers for liver toxicity, miricorilant appears to mitigate it. The current results are suggestive, although it is buttressed by earlier animal work.

With mice given a high-fat diet, miricorilant reverse liver accumulation of triglycerides and cholesterol. It also reduced liver inflammation and liver weight. Lastly, miricorilant encourages outflow of pathogenic lipids. All these would serve to reduce the liver’s overall toxicity profile.[2]

If this drug trait gets firmly established, then miricorilant becomes an especially interesting candidate for combination therapy. Many NASH drugs are toxic to the liver. We see NASH drugs that lack side effects, especially liver-related effects, being good candidates. Miricorilant takes it further.

Intellectual Property


CFO Charlie Robb once again confirmed his guidance about the expected court timelines. Teva seeks to market generic Korlym, and Corcept sued Teva for patent infringement.

Teva has asked the patent office to review the validity of Corcept’s patent regarding the concurrent administration of Korlym and CYP3A inhibitors. This is for a special (post-grant) review from the Patent Trial & Appeal Board (PTAB). We think the odds are good that the courts initiate a post-grant review (PGR). CFO Charlie Robb confirmed this expectation on the conference call.

Within November 2019, we should discover whether the PTAB grants the PGR. If the PTAB grants the PGR, this legal situation may create an additional millstone around Corcept’s valuation. We do not think it changes much. While outside legal commentary is focused on “victory”, we are much more concerned with “delay”.

It’s inevitable that a generic Korlym will someday be allowed onto the market. The key issue is when generic Korlym arrives versus the timing of relacorilant’s market launch. With the PGR litigation and subsequent appeal, then the whole process may resolve in April 2021 or even a couple months later.

We hoped that relacorilant’s NDA would be submitted earlier in 2021. If Teva prevails in the patent courts, then it could have a limited opportunity to enter Corcept’s current market…until relacorilant arrives.

Milestones


Corcept Sponsored Trials
Metabolic Indications
While Cushing’s syndrome is a recognized indication, its successful treatment by Korlym should be viewed as “proof of concept” for working in other metabolic indications involving diabetes, obesity, and high blood pressure. This would be especially true with mild cases of Cushing’s syndrome involving small benign tumors on the adrenal gland (adrenal incidentalomas).
Cushing’s Syndrome
There are perhaps 7,000 to 10,000 patients in the USA that could benefit from Corcept’s drugs. Nevertheless, the diagnostic category may greatly expand with middle-aged and older adults who are impacted byadrenal incidentalomas. This used to be called “subclinical Cushing’s Syndrome”. Korlym or a next-generation drug targets the metabolic consequences of the disease.

Relacorilant (AKA CORT125134) is a next generation, selective GR-antagonist. It is good at blocking the glucocorticoid receptor (GR), but unlike Korlym it does not block the progesterone receptors (PR). It lacks some of Korlym’s off-target effects, especially its ability to terminate pregnancies. 

Grace Pivotal Study

The GRACE Pivotal study involves two phases: an open-label (OL) phase and a randomized-withdrawal (RW) phase.

Patients will dose-escalate in 100 mg increments to a target dose of 400 mg orally once daily during the open-label phase. Patients will remain on open-label treatment until week 22 at which time they will be evaluated for the randomized-withdrawal phase based on pre-defined hyperglycemia and hypertension response criteria.

Eligible patients will then be randomized to receive either relacorilant or placebo at a 1:1 ratio for 12 weeks.

It is currently unknown whether Corcept will release the open-label results in 2019 or 2020. The open-label results are key: patients will be later withdrawn off relacorilant and assuredly relapse.

Adrenal Adenoma – Less Severe Cushing’s (LSC)

This study focuses on LSC patients. Scanning technology continues to get faster better cheaper…and this enables the detection of small tumors on the adrenals. This impacts metabolic symptoms and osteoporosis.

Although precise estimates do not exist, the existing studies suggest that the patients with “less severe Cushing’s” outnumber the traditional (severe) Cushing’s patients.
  Phase 3 GRACE STUDY Results– Randomized Withdrawal
  Relacorilant vs. Placebo – 130 pts
1H-2021
  Open-Label Extension Final Results – Relacorilant – 75 patients
Q3-2021
  Phase 3 Adrenal Adenoma – Launch – Two Treatment Groups
  Relacorilant vs. Placebo – 130 LSC pts – 22 weeks
Q1-2020
  Phase 3 Adrenal Adenoma – Results – Two Treatment Groups
  Relacorilant vs. Placebo – 130 LSC pts – 22 weeks
Q3-2021
  FDA (New Drug Application) Submission – Relacorilant
Q4-2021
Miricorilant (CORT118335)

CEO Belanoff stated that miricorilantproduced 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.

Why miricorilant rather than Korlym?

1. In animal models, miricorilant has a stronger, more potent effect on mitigating antipsychotic impacts on weight and other metabolic functions;
2. miricorilant has a preferential uptake into the liver (fat) and does a better job at reducing pathogenic forms of liver fat;
3. And like relacorilant, it lacks some of Korlym’s annoying side effects and won’t cause abortions.

Years ago, we also underscoredmiricorilant’s ability to treating alcohol use disorder in animalmodels. It is better than Korlym and other candidate drugs at reducing continued drinking in alcoholic rodents.

Miricorilant is the first drug in the clinic from its platform. Relacorilant and exicorilant belong to another platform and they were designed to be like Korlym (mifepristone). Miricorilant has selected and potent effects.

In sum, miricorilant reduces obesity and insulin resistance, flushes out unhealthy forms of fat and triglycerides out of the liver, reduces liver tissue damage and inflammation. There appears to also be some cholesterol lowering activity, but it’s the result of efflux, rather than preventing cholesterol production (like a statin).
Antipsychotics and Weight Gain (Metabolic Syndrome)

The prevention of weight gain and the degradation of other metabolic markers is a very large market.  Popularly prescribed antipsychotics creates well-documentedharm. For example, the average 1st year, adult weight gain on Zyprexa is about 20 pounds!Ms of U.S. residents are currently consuming antipsychotics.

In human trials, Corcept has already demonstrated Korlym’s and CORT108297’s ability to mitigate the harmful metabolic consequences (i.e. weight ↑, cholesterol ↑, insulin resistance ↑) with antipsychotics. In animal models, miricorilant is more potent than mifepristone (Korlym). It also does things that mifepristone can’t.

Among patients that take olanzapine, mifepristone patients gained significantly less weight than placebo patients(p < 0.0001). Similar results were found among patients who take Risperidone; furthermore, the mifepristone patients were protected against degradation of fasting insulin and triglyceride levels.

Corcept’s drugs have an immediate beneficial impact on metabolic markers, independent of weight! Cholesterol ↓ and insulin resistance ↓ goes down, while weight is gradually restored.

This is a well-documented niche and miricorilant enters with decidedly greater proof-of-concept than Corcept’s foray into the cancer indications.

Compared to general obesity meds, the FDA will look kindly on this indication. The patients are viewed as "victims" of medical treatment.

Healthy Patient Trial

Healthy males are in a randomized, double-blind, placebo-controlled study. All patients are given 10mg / day of olanzapine, while the “treatment groups” receives 600 mg/day or 900 mg/day of miricorilant.

The study will track multiple safety and metabolic metrics. It will also test and optimize different formulations of miricorilant. It is managed by the same British CRO that performed the Phase 1 on CORT125134 and Phase 1b on CORT118335. We expect all patients will be recruited within the U.K.
 Phase 1b ResultsOlanzapine Weight Gain Prevention
  Healthy Men – Miricorilant 900 mg qd
Jan 2021*
 Phase 2 ResultsAIWG –“Recent Weight Gain” Reversal Results
  100 Schizophrenics on olanzapine, risperidone, or quetiapine
  Miricorilant vs. Placebo
Dec. 2020
 Phase 2 ResultsAIWG –“Chronic Obesity” Reversal Launch
  100 Schizophrenics on olanzapine, risperidone, or quetiapine
  Miricorilant vs. Placebo
Q1-2021*
Non-Alcoholic Steatohepatitis (NASH)

With respect to liver fat, fibrosis, and NASH, the animal model results with CORT118335 are impressive. Corcept’s patent for treating fatty liver disease is published in the US and Europe.

CORT118335 eliminates pathogenicwhite fat. Rats fed the “McDonald’s Diet” have a much more comprehensive response to CORT118335 versus Korlym. While the Korlym halted insulin resistance and other markers, CORT118335 additionally prevented “bad fat” deposits.  The CORT118335 mice had “reduced caloric efficiency”, which means that energy was being expended instead of being stored as fat or carbohydrates.

Recently published animal models show that CORT118335 prevents and reverses fatty liver disease. When fed a high fat diet, the biopsies present a striking contrast between the CORT118335 mice versus “regular” mice. The internal system, including the liver, looks relatively lean.

In “human models” involving Cushing’s syndrome, Korlym reduces weight and apparently reverses fatty liver disease.

We expect these patients to be obese and thus the weight reduction alone should improve many livers as well as overall health. The propensity of CORT118335 to target the liver and reduce bad fat also bodes well for this pilot trial. Because of the prior human data, we nevertheless have greater confidence in the antipsychotic-induced weight gain (AIWG) program.
  Phase 2 Launch – NASH Treatment / Metabolic Syndrome
  Miracorilant 600 mg qd  or placebo - 120 Pts with Probable NASH
1H-2020
  Phase 2 Results – NASH Treatment / Metabolic Syndrome
  Miracorilant 600 mg qd  or placebo - 120 Pts with Probable NASH
Mid-2021
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, but cortisol is an opposing force.

Corcept’s drugs should reverse and downregulate the “apoptosis suppressing genes”.  This restores chemotherapies’ original 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 robust interest in immune system modifiers to fight cancer. Corcept’s drugs additionally have a mild side effect profile. This makes for strong combination therapy candidates..
Solid Tumors
CORT125134 (relacorilant) is in a Phase I/II trialto treat solid tumors including breast and ovarian cancer. In the Phase I part, relacorilant 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 andearly clinical datafor 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. 
  Ongoing Phase IIa Results – Expansion Cohorts (~24 pts per Cohort)
  146 total pts, Abraxane (80 mg/m2) + Relacorilant (100 mg/ daily)
  Ovarian, Triple-negative breast, Pancreatic, Other
TBA
Pancreatic Cancer Program

In the ongoing Phase 1b trial of relacorilant + Abraxane, 4 of 9 pancreatic cancer patients had durable disease control with a partial responder having progressed earlier on Abraxane combination therapy. Furthermore, all patients had aggressive metastatic disease and were taxane-resistant. Responders tended to have high GR expression.

A hypothesized pivotal trial will recruit a very tough group of patients: we think many, if not most, patients will be abraxane-resistant. We also think this will be the first major study involving several patients with 3+ prior lines of therapy. This is a test of Corcept’s drugs for fighting GR++ resistant cancer. It doesn’t get much tougher than this.
  Phase 2b Trial Launch – Pancreatic Cancer
  Abraxane ± Relacorilant 
Q1-2020*
Ovarian Cancer
Corcept launched an open-label, randomized and controlled, Phase 2 trial of relacorilant plus Abraxane in metastatic ovarian cancer. The primary endpoint is progression-free survival in patients with recurrent platinum-resistant cancer.

Platinum-resistant ovarian cancer patients are randomized 1:1:1 to one of three treatment arms. Patient randomization will be stratified by treatment-free interval from most recent taxane (<6 months="" vs="">/=6 months) and presence of ascites (yes vs no).

Arm A (Continuous): Relacorilant 100mg, administered orally, once daily every day starting on Cycle 1, Day -7 in combination with nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle.
Arm B (Intermittent): Relacorilant 150mg, administered orally, on the day before, the day of, and the day after nab-paclitaxel, starting on Cycle 1, Day -1, in combination with nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle.
Arm C (Comparator): Abraxane on Days 1, 8, and 15 of each 28-day cycle.

Patients in Arm C with definite progressive disease may be later offered relacorilant + Abraxane. Platinum resistant ovarian cancer has a tough prognosis: the response rate is 10% to 15%, and overall survival is only 12 months. For this trial, the expected length could be even shorter. The holy grail is to increase efficacy without overwhelming toxicity.

In the previous Phase 1b trial of relacorilant + Abraxane, 4 of 7 ovarian cancer patients had durable disease control (CR, PR, or SD). There was 1 CR and 1 PR. Furthermore, all patients had aggressive metastatic disease and were taxane-resistant.
Abraxane + Relacorilant - 177 pts with platinum resistant cancer
TBA
  Abraxane + Relacorilant - 177 pts with platinum resistant cancer
2023
Prostate Cancer Program

There will be close attention from the cancer community on trialsinvolving GR antagonists for treating prostate cancers that are resistant to enzalutamide and abiraterone.

Three different GR drugs are being tested with castration-resistant prostate cancer:
       1)Exicorilant (CORT125821) – Corcept-Sponsored Trial
       2)Relacorilant (CORT125134) – University of Chicago Trial
       3)Mifepristone – University of Chicago Trial

Corcept expects the trials’ results to arrive in 2020.

Exicorilant Trial

CEO Belanoff mentionedexicorilant(CORT125281) stood out with treating rodent models of prostate cancer including castrated animals.

This trial pairs exicorilantwith enzalutamide(Xtandi)to treat 80 mCRPC (metastatic, castration-resistant prostate cancer) patients. The study aims to find the maximum tolerated dose (MTD) of the combination therapy. One cohort of patients progressed on prior treatment with enzalutamide or other advanced AR-blocking therapies.
  Decision to Green Light a Phase 2b Trial
1H-2020
  Phase 1/2a Ongoing Results Open-Label, Dose-Escalation
  Xtandi + Exicorilant - 80 Metastatic Castration Resistant
Mid-2020*
  Phase 1/2a Final ResultsOpen-Label, Dose-Escalation
  Xtandi + Exicorilant - 80 Metastatic Castration Resistant
Q3-2021*
    *Guesstimate 

Independent Investigator Sponsored Trials
Cancer Program
Advanced GR+ Triple Negative Breast Cancer
Patients are treated in a randomized, double-blinded, placebo-controlled design.
  Phase 2 Results - University of Chicago
  Abraxane ± Mifepristone – 64 pts
1H-2020*
The open-label study will include a safety lead in of ten patients. Patients who are deemed eligible and have signed informed consent will be treated with pembrolizumab(Keytruda) at a fixed dose of 200 mg intravenously on day 1 of each 21-day cycle for each dose level. Mifepristone 300mg PO will be administered daily starting the week prior to pembrolizumab.

Pembrolizumab is an approved anti-PD-1 mAb, marketed by Merck.

The first cohort of 10 patients will be evaluated for safety (Phase 1). During dose expansion, the study will include triple-negative breast cancer patients. After successful Phase 1 safety is passes, then both cohorts will be subjected to dose expansion.

Cohort 1: Hormone receptor positive, treatment refractory breast cancer (25 to 34 pts)
Cohort 2: Triple Negative breast cancer (27 to 40 pts)
  Phase 2a – Final Results - University of Chicago - Dose Escalation
  Pembrolizumab + Mifepristone - 74 pts
Q4-2020*
Prostate Cancer Program

Mifepristone Study

Patients are given Xtandi vs. Xtandi + Mifepristone. While these patients failed prior therapy, they are naïve to 2nd generation AR antagonists (Xtandi, AR509).

The University of Chicago investigators are often slow to release results. We expect the results to be presented at an academic conference.

Relacorilant Study

In the other study, relacorilant is combined with Xtandi to treat metastatic castration resistant prostate cancer (mCRPC) in an open-label design. Enrolled patients will have prior treatment with at least one line of enzalutamide (Xtandi), apalutamide (Erleada), or abiraterone (Zytiga).

24 patients will be enrolled in 6 patient cohorts with a 6+3 design and a 28-day DLT period. Doses of relacorilant, enzalutamide will be adjusted based on safety and pharmacokinetics (PK). Once a safe dose with appropriate drug levels (PK) has been established, the cohort will be expanded to a total of 12 patients to refine safety and PK at the recommended phase II dose (RP2D).
  Xtandi ± Mifepristone - (University of Chicago) - 108 pts
1H-2020*
  Xtandi + Relacorilant – (University of Chicago) – 24 pts
Mid-2020*
Advanced Non-Small Cell Lung Cancer
This is an open-label design, in patients with metastatic NSCLC who have failed 2+ prior chemotherapies. Mifepristone as a monotherapy must increase the median progression-free survival time past 15 weeks and overall survival > 16 months. We are queasy because we do not view Corcept’s drugs as monotherapies for treating cancer.
  Phase 2a Top-line Results - Cooper Institute
  Mifepristone Monotherapy - 40 pts -300 mg qd in 28-day cycles
Q1-2022*
Addiction Disorders
Recentcommentaryimplicates the use of glucocorticoid antagonists, including mifepristone, for treating general addiction problems.
Alcohol Withdrawal – Prior Phase IIa studyreported positive results with untreated alcoholics. There is also an “observational” studyin which cortisol levels predicted the drinking intensity in alcoholics.

There are some impressive research labs, including the current NIAAA Director’slabat UCSD, that have been using Corcept’s drugs for alcohol withdrawal.
  Phase 2 Results– Scripps, San Diego
  Mifepristone vs. Placebo, 103 pts, 600 mg, 1200 mg qd; 7 days
Q1-2020*
  Phase 1/2 Results - Brown University
  Mifepristone – 30 pts - Crossover, Double-Blind, 600 mg qd; 7 days
January 2021*
  Phase 2 Results - Johns Hopkins
  6 doses of Mifepristone vs. Placebo, 150 pts
Q1-2022
Metabolic Syndrome
A recent study treated patients who suffered from benign adrenal incidentalomas(adrenal tumors) with diabetes and mild hypercortisolism. Mifepristone treated patients experienced: decreased waist size and insulin resistance, and improved quality of life. These (very) mild cases of Cushing’s syndrome should be viewed as a human proof of concept for treating other forms of metabolic syndrome.
Diabetes, Obesity
  Phase 2 Results – Charles Drew University of Medicine
  Poorly Controlled Type 2 Diabetics sans Cushing’s 
  Mifepristone - 60 male pts
Mid-2020
  *Guesstimate  


Our Thoughts


There were multiple positives: stronger sales; positive clinical results; and program updates. While most investors will be focused on sales and the intellectual property court case, the big news is really about the positive results for treating antipsychotic induced weight gain. This is a blockbuster market and Corcept is attempting to shepherd the first approved drug for this indication.

Given that miricorilant was administered in a “less than ideal” fashion, the results are even more impressive. A low dose of miricorilant was tested within a brief treatment period of only 14 days. Furthermore, the blood levels fell way short of the optimal target. We expect the higher dose cohort results to be even more impressive.

While we are very interested in the full suite of AIWG trials to treat obese schizophrenics, the leap from rodents to human was big. It’s much bigger than the leap from healthy humans to schizophrenics. We have little reason to think that the metabolic processes are significantly different for schizophrenics versus “healthy normal”.

The new task is about decoding the nuances of miricorilant’s effectiveness with schizophrenics. Will it improve the metabolic metrics in obese schizophrenics? This may be a higher bar than prevention. Before any handicapping is done, we await the higher dose cohort data in healthy normals.

If it's good, then the Corcept story changes yet again for the casual observer.

(At the time this post was written, one or more BioWatch authors held a position in CORT)





[3]Koorneef LL, et al. (2018) Selective Glucocorticoid Receptor Modulation Prevents and Reverses Nonalcoholic Fatty Liver Disease in Male Mice. Endocrinology, 159, 3925-3936, doi: 10.1210/en.2018-00671


Original Article: Corcept Therapeutics - Q3-2019 Highlights - Clinical Results

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