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No Surprises - Corcept Therapeutics - Q1-2019 Results

08:52 EDT 10 May 2019 | Biotech Watcher


On Thursday, May 9, 2019, Corcept Therapeutics (CORT) reportedQ1-2019 results and held a conference call.

The reported Korlym sales will be viewed as disappointing to some; the underlying (mild Q1) growth in patients is mitigated by insurance reauthorizations and larger medicare “donut hole”. We expect The Pancreatic Cancer trial decision to be announced with updated results at ASCOin early June 2019. Corcept has also launched its antipsychotic-induced weight gain (AIWG) program. 

Background Readings


Corcept Q4 & FY-2018 Results (February 26, 2019)

Financial Summary


Quarter Ending March 31, 2019
(in Thousands except Share Price & Market Cap)

Q1-2019
Q4-2018
Q3-2018
Q2-2018
Q1-2018
Net Product Sales
$64,829
$66,831
$64,445
$62,312
$57,269
Cost of Sales
1,240
1,579
1,308
1,154
1,174
R&D Expense
20,244
18,794
18,860
20,543
17,050
SG&A Expenses
24,389
21,560
21,308
19,981
18,440
Total Operating Expenses
45,873
41,933
41,476
41,678
36,664
Net Income (Loss) from Operations
18,956
24,898
22,969
20,634
20,995
Net Income (Loss)
18,274
22,008
17,747
18,196
17,459
Total Comprehensive Income
18,438
22,015
17,797
18,221
17,307
Basic & diluted income (loss) per share
0.16
0.15
0.19
0.18
0.15
0.14
0.16
0.14
0.15
0.14
Avg. Shares Outstanding
Basic & Diluted
114,844
123,895
115,191
125,152
115,798
126,159
115,492
127,515
114,882
127,733
Recent Price (per share)
12.23
(5/9/19)
11.49
(2/25/19)
12.23
(11/1/18)
13.98
(8/9/18)
17.36
(5/8/18)
Market Capitalization
1.4B
1.3B
1.4B
1.6B
2.0B
Cash
49,650
41,625
33,894
31,165
33,121
Short-term Marketable Securities
137,255
128,780
161,300
128,780
92,241
Long-term Marketable Securities
28,842
-
1,481
-
73
During Q1-2019, Corcept repurchased 1.2M shares of common stock under its Stock Repurchase Program in open market transactions at an average price of $11.61 per share, for an aggregate purchase price of $13.6M. Shares repurchased are recorded as treasury stock at cost on the consolidated balance sheet. As of March 31, 2019, $62.8M remained available for the repurchase of CORT shares.

The management stated that it has enough profits to complete its ongoing development programs.

Net Sales
Q1-2019
Q4-2018
Q3-2018
Q2-2018
Q1-2018
2018
Total
2019
Total
FY-2019
Guidance
$64.8M
$66.8M
$64.4M
$62.3M
$57.7M
251.2M
$64.8M
$285M-$315M






Management confirmed earlier guidance: net sales of $285M to $315M for FY2019, and we still “guesstimate” that Corcept will hit the lower end of guidance. The Q1 revenues are temporarily reduced as patients must secure reauthorizations with their health insurance. Of greater import is the Medicare Part D insurance reimbursement - the “donut hole” with a larger coverage gap for 2019. It’s supposed to narrow in 2020 but… 

In contrast to prior years, Corcept did not raise the price. There is less shielding from the impacts of insurance reauthorizations and the Medicare “donut hole”. The number of patients on Korlym continues to increase, and the steady rise should resume with Q2-2019 sales results.

Corcept’s sales growth is flattening and the fluctuations due to expenses and reimbursements will sometimes mask the actual underlying growth. We mentioned this before. We suspect the market will see this as a disappointment, especially those invested in a Corcept that has growing profits.

About Corcept and Its Cushing’s Market


In the short-terms, we will see slowly increasing revenues with a bit more of a “jump” from Q1-2019 to Q2-2019. We affirm our earlier impressions, that CORT revenues will just hit $285M. We still expect the quarterly revenues to exceed $75M and even more, but that day isn’t today. The sales growth for 2019 and 1H-2020 will continue to be mild.

The longer-term sales prospects hold strong potential. In the short-term, however, Corcept will be content with a $200M-$250M annual budget. 

Cushing’s Market Sales Prospects


Management expects the markets to increase for several years. Physicians will increasingly understand the dynamics of hypercortisolism and the negative impacts of forestalling treatment.

We agree with management; the Cushing’s market has more “juice”.

First, relacorilant is superior to Korlym and if its recent results are repeated, then the market expansion will be robust. Korlym has the social stigma of the “abortion pill”. This prevents its use within clinics in conservative areas of the United States. Relacorilant will also be marketed in the European Union. We then expect peak sales to exceed $500M.

Second, the assay test has arrived. Endocrinologists want a test that monitors ongoing disease status – Corcept’s test is a step forward from the current tests of cortisol activity.

Third, recent studies imply extensions to the standard Cushing’s market – small studies involving very specific segments are enticing: preoperative Cushing’s patients; non-cancerous adenomas with “mild” disease; diabetics with adenomas; hypertense diabetics, and more.

For example, we recently wrote the following for general diabetes:

Steffensen and her colleagues performed a systematic review on the frequency of hypercortisolism in type 2 diabetics (T2Ds). Out of 2,827 T2Ds, 3.4% had excessive cortisol levels and 1.4% had Cushing’s syndrome.

This is low-hanging fruit…

Specific segments within T2D appear to hang even lower.

Patents

Patent US9943526 (B2) Optimizing Mifepristone Levels in Cushing’s Patients
Patent US10195214 (B2) Concurrent Administration of GR Modulators and CYP3A Inhibitors

Patent US10231983 (B1) Use of ACTH in assessment and prophylactic treatment of hypokalemia associated with glucocorticoid receptor modulator treatment of CS patients

Patent US10151763 (B2) Treatment and differential diagnosis of Cushing's disease and ectopic Cushing's syndrome

Patent Application US2018256604 (A1) Use of Glucocorticoid Receptor Modulators in the Treatment of Catecholamine-Secreting Tumors

Patent Application US2018125856 (A1)Use of Glucocorticoid Receptor Antagonist and Somatostatin Analogues to Treat ACTH-Secreting Tumors

Patent US9829495 (B2) Method for differentially diagnosing ACTH-dependent Cushing's syndrome

Patent Application US2018078565 (A1) Use of GR Antagonists with Steroids to Treat Adrenal Insufficiency

The Generic Korlym Case


While, some of these patents and apps have varying mileage, the Corcept defense strategy is clear. It’s forcing Teva and others into a skinnier and skinnier label. We expect further IP from Corcept.

First, there is precedent for Corcept's patent strategy. Jazz Pharma successfully positioned a "similar" IP situation to create a strong case. This got incorporated into the Xyrem label and this ruled out the plaintiff’s "carve-out" to create a skinny label for the generics. This is a serious consideration.

It’s hard to tell whether the courts will rule in Corcept’s favor. It looks like Corcept is positioned better than Jazz, but we should assume caution. However, the new patents increase the complexity and may enable further delay to a verdict. Every week counts.

Second, "delay" equals a win for long-term investors. Relacorilant is looking like a winner and even if Teva and others prevail, generic Korlym is confined to a small niche. It will be for patients who don’t respond to relacorilant, or are comfortably stabilized on Korlym. The generics companies must also avoid infringing on Corcept’s patents.

CFO Charlie Robb confirmed his earlier thoughts almost verbatim about the expected court timelines. We don’t expect a verdict on the Teva suit before Q1-2021.An appeal process and final verdict would probably take another 6 to 12 months.

Neptune Generics, a subsidiary of Burford Capital, filed an IPR, an Inter Partes Review, to challenge another of Corcept’s patents. The Patent Trial & Appeal Board (PTAB) should reach its decision in a year, and the loser may appeal. The appeal typically adds 6 to 12 months. CFO Charlie Robb thus expects that the “earliest we expect final resolution of this IPR is Q3-2020”.

Thirdwe expect an eventual settlement so that Teva forks over a small percentage of revenue to Corcept and takes responsibility for defending the intellectual property.  

We’re about 75% sure.

Ironically, Teva can then take Corcept’s role and beat down other generics companies. We don’t expect a settlement before relacorilant’s GRACE study results are finished, probably Q1-2021. It can certainly happen before this event, but this is our best guess…if it happens.

ASCO Results


Corcept is currently conducting a Phase 1/2 of relacorilant + Abraxane to treat a variety of solid tumors. While we initially thought that Corcept launched expansion cohorts in multiple indications (e.g. checkpoint inhibitor), that does not appear to be the case. In its latest update, the focus has been on enrolling pancreatic cancer patients.

The following will be presented at ASCO 2019:

Updated Ovarian & Pancreatic Cancer Results (June 3, 2019)
Solid Tumors – First Results

While we hoped to see results from an array of expansion cohorts, the focus on pancreatic cancer is unsurprising. Corcept must architect a satisfying trial design for the FDA, it’s entering uncharted waters. There is a lack of good metrics and comparisons to establish approvable efficacy.

During the conference call, we read between the lines of the conference call, we think the updated results in ovarian and pancreatic cancer will be similar to prior releases. The prior results form part of the updated dataset, and so we don’t think we’re too far off with our interpretation.

Nevertheless, even though the previous pancreatic cancer data signaled efficacy, this contrasts with having enough context to establish approvability in the next trial.

Antipsychotic-Induced Weight Gain (AIWG)


Patent US9321736 (B2) Pyrimidine cyclohexyl glucocorticoid receptor modulators
(Composition of Matter Ends November 7, 2034)

Patent US6680310 (B2) Methods for preventing antipsychotic-induced weight gain
(Ends July 22, 2022)

Antipsychotics degrade metabolic processes in humans. Obesity is the most visible and concrete metric. There are also impacts on cholesterol, triglycerides, insulin resistance and blood sugar levels. Corcept’s drugs are deployed with metabolic syndrome indications.

There is already direct evidence of mifepristone’s benefits in treating diabetic and fatty liver patients,[1] as well as preventing and reversing antipsychotic-induced weight gain (AIWG). CORT108297 was also successfully tested in humans.

For this clinical trial program, Corcept is advancing miracorilant AKA CORT118335.

New AIWG Clinical Trials


Corcept intends three AIWG clinical trials.

2H-2019 Antipsychotic-Induced Recent Weight Gain Reversal - Schizophrenics
Q4-2019 Olanzapine-Induced Weight Gain Prevention Results – Healthy Patients

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.

We have written about the drawbacks and the class action lawsuits elsewhere. How bad is this problem? Short answer: it’s very bad.[2]

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 should benefit from this treatment..

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.It enjoys orphan designation within the USA and the European Union.

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. We think that’s the much more important set of results, because patients that are later withdrawn off relacorilant will assuredly relapse.
Phase 3 GRACE STUDY Results– Randomized Withdrawal
139 Patients -
Relacorilant vs. Placebo
1H-2021*
Regulatory Submission
Q3-2021*
Miracorilant (CORT118335)

CEO Belanoff stated that miracorilantproduced 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 miracorilant rather than Korlym?

1. In animal models, miracorilant has a stronger, more potent effect on mitigating antipsychotic impacts on weight and other metabolic functions;
2. Miracorilant 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 underscoredmiracorilant’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.

Miracorilant is the first drug out of a separate platform. Relacorilant and CORT125281 belong to another platform and they were designed to be like Korlym (mifepristone). miracorilant has selected and potent effects.

In sum, miracorilant 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).

In each of the clinical trials, there are three treatment conditions:

High Dose Miracorilant – 600mg
Low Dose Miracorilant – 200mg
Placebo
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! Millions 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, miracorilant 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 miracorilant 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

64 healthy males are in a randomized, double-blind, placebo-controlled study. All patients are given 10mg / day of olanzapine, while the “treatment group” receives 600 mg/day of miracorilant.

The study will track multiple safety and metabolic metrics.  It is managed by the same British CRO that performed the Phase 1 on CORT125134 and Phase 1b on miracorilant. We expect all patients will be recruited within the U.K.
Phase 2a ResultsProfile of Miracorilant Metabolites
12 Healthy Men
Q2-2019
Phase 1b ResultsOlanzapine Weight Gain Prevention
64 Healthy Men – Miracorilant 600 mg / day
December 2019
Phase 2 Launch – Antipsychotic – Recently-Established Weight
Gain Reversal -Miracorilant daily 200 mg or 600 mg vs. Placebo
135 Obese Schizophrenics on olanzapine, risperidone, or quetiapine[3]
Q4-2019
Phase 2 LaunchAntipsychotic – Long-Standing Weight Gain
Reversal - Miracorilant daily 200 mg or 600 mg vs. Placebo
135 Obese Schizophrenics on olanzapine, risperidone, or quetiapine
Q4-2019
Phase 2 ResultsAntipsychotic – Long-Standing Weight Gain
Reversal - Miracorilant daily 200 mg or 600 mg vs. Placebo
135 Obese Schizophrenics on olanzapine, risperidone, or quetiapine
Q4-2020*
Non-Alcoholic Steatohepatitis (NASH)

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

Miracorilant eliminates dangerouswhite fat. Rats fed the “McDonald’s Diet” have a much more comprehensive response to miracorilant versus Korlym. While the Korlym halted insulin resistance and other markers, miracorilant additionally prevented “bad fat” deposits.The miracorilant 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 miracorilant prevents and reverses fatty liver disease. When fed a high fat diet, the biopsies present a striking contrast between the miracorilant 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 miracorilant 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 2a Results – NASH Treatment / Metabolic Syndrome
120 Pts with Probable NASH - Miracorilant daily 200 mg or 600 mg
2H-2020*
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 trialto 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 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 Ib Results –Relacorilant (100 mg/ daily) +
Abraxane (80 mg/m2) - 20 Patients with Pancreatic Cancer
ASCO 2019
Early June
Phase IIa Results – Expansion Cohorts (~24 pts per Cohort)
Relacorilant + Abraxane (triple-negative breast cancer)
Relacorilant + Pembrolizumab(Keytruda)
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 indication is a robust test of Corcept’s drugs for fighting GR++ resistant cancer. It doesn’t get much tougher than this.
Phase 2b Trial Decision
Relacorilant + Abraxane (Pancreatic Cancer)
ASCO 2019
Early June
Ovarian Cancer
Corcept is 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.
Relacorilant + Abraxane - 177 pts with platinum resistant cancer
TBA
Relacorilant + Abraxane - 177 pts with platinum resistant cancer
2023
Prostate Cancer
CEO Belanoff mentionedexicorilant(CORT125281) stood out with treating rodent models of prostate cancer including castrated animals. There will be close attention from the cancer community on trialsinvolving GR antagonists for treating prostate cancers that are resistant to enzalutamide and abiraterone.

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.
Phase 1/2a Ongoing ResultsExicorilant+ Xtandi
Dose Escalation - 80 Metastatic Castration Resistant (Open Label)
2019
Decision to Green Light a Phase 2b Trial
Q4-2019
Phase 1/2a Final ResultsExicorilant+ Xtandi – Dose Escalation
80 Metastatic Castration Resistant Prostate Cancer (Open Label)
Mid-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 II Results(University of Chicago) (64 pts)
Korlym + Abraxane
Q4-2019
Advanced HER2-negative Breast Cancer & Checkpoint Inhibitor
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)
Pembrolizumab + Mifepristone - (University of Chicago) (74 pts)
Q4-2020*
Prostate Cancer

Mifepristone Study

In the Phase 2 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 sometimes slow with releasing their results. The investigators will wait to present at their chosen 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
Corcept is listed as a collaborator in the study. It is an open-label design, in patients with metastatic NSCLC who have failed 2+ prior chemotherapies. It is hoped that mifepristone as a monotherapy will increase the median progression-free survival time to 15 weeks and overall survival time of 16 months. We are a bit queasy because we do not view Corcept’s drugs as monotherapies for treating cancer.
Phase II Top-line Results(Cooper Institute) (40 Pts)
300mg/day in 28-day cycles
Q4-2019*
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 with alcohol withdrawal. Nevertheless, we don’t expect Corcept to initiate an in-house program before 2019. We speculate that management will wait until the metabolic program has returned some Phase 2 results, which enables a closer look at the effect of Corcept’s drugs on the liver.
Phase II Results(Scripps – San Diego) (150 pts)
Placebo, 600 mg, 1200 mg/day; 7 days
Q3-2020*
Phase I/II Results(Brown University) (20 pts)
Crossover, Double-Blind, 600 mg/day, 7 days
Dec. 2019*
Phase II Resultsin Heavy Drinkers (Johns Hopkins) (150 pts)
6 doses of Mifepristone vs. CORT125134 vs. Placebo
Q1-2022
Tobacco Use Disorder - Mifepristone may be a potential treatment for Tobacco Use Disorder (TUD). No previous studies have examined the therapeutic potential of mifepristone for TUD. There is indirectevidenceincluding the relation between cortisol levels and nicotine craving. but this study is a first attempt at exploring a direct intervention.

This is a double-blind, placebo-controlled design on the effects of a 7-day treatment with 600 mg mifepristone, or placebo, on cognitive function, tobacco withdrawal severity, and smoking behavior.
Phase 1a Results(Yale University) (40 pts)
600mg, daily, for 7 days
Q4-2019*
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 II Results– Poorly Controlled Type 2 Diabetics sans
Cushing’s (Drew University) - (60 pts)
Mid-2020
*Guesstimate

Our Thoughts


There weren’t any surprises with Corcept’s Q1-2019 results and guidance. Corcept remains a developmental biotech that is going for several doubles and triples in treatment-resistant cancers and metabolic diseases. It also markets an approved drug that should bring $590M over the next two years.

This has enticed challenges to Corcept’s patents, so that the plaintiffs can market “Generic Korlym”. This should be resolved no earlier than early 2021 with an appeal enabling a final verdict about 6 to 12 months afterwards.

We expect relatively mild sales growth to continue for the next several quarters. There will be bottom-line fluctuations across quarters, and with the Q1-2019 sales results, some investors will be disappointed. For them, the underlying story won’t matter.

…nevertheless, the story hasn’t changed. The ongoing sales funds an ambitious pipeline and enabled profitability. If Corcept loses the court cases in 2021, then it still has other near-term valuation drivers: relacorilant phase 3, results; and ovarian cancer phase 2b results. There might additionally be: pancreatic cancer phase 3 results; and metabolic program phase 3 launches.

A decision to go straight into a pancreatic cancer pivotal trial would therefore be especially good news. We expect that the pancreatic program will progress; it’s just a question of speed.

The next clinical results will be released at ASCO in early June 2019. We expect positive signals for treatment-resistant ovarian and pancreatic cancer. These are notoriously difficult indications; we should not expect eye-popping response rates. Stable disease is a win, and partial responses are a strong win.

In 2019, the clinical trial results that holds special interest is miracorilant to prevent antipsychotic-induced weight gain in healthy volunteers. The valuation may not significantly move with good news.[4] Positive results should nevertheless be viewed as a harbinger for a subsequent trial involving schizophrenics with recent weight gain.

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



[1]Macfarlane DP et al. (2014) Effects of acute glucocorticoid blockade on metabolic dysfunction in patients with Type 2 diabetes with and without fatty liver. American Journal of Physiology-Gastrointestinal and Liver Physiology, 307, G760-G768. Also Ragucci E et al. (2017) Effects of Mifepristone on Nonalcoholic Fatty Liver Disease in a Patient with a Cortisol-Secreting Adrenal Adenoma. Case Reports in Endocrinology, https://doi.org/10.1155/2017/6161348.
[2]Prospective studies revealed that the average weight gain during the first year of treatment was 11.7 to 13.9 lbs for clozapine, 15 to 26 lb for olanzapine, 4.4 to 5.1 lb for risperidone, 6.1 to 13.3 lb for quetiapine…” from Wick, J. and Zanni, G. (2019). Drug-induced Weight Gain: Schizophrenia and Antipsychotics. [online] Pharmacytimes.com. Available at: https://www.pharmacytimes.com/publications/issue/2006/2006-07/2006-07-5677 [Accessed 25 Feb. 2019].
[3]Olanzapine (Zyprexa) – Eli Lily settled landmark class actions over the years for Olanzapine’s strong propensity to cause gross weight gain and increase diabetic risk. This was the motivation for Eli Lily to help fund Corcept’s original olanzapine clinical trials. It remains one of the most popularly prescribed first-line antipsychotics with 2.3M prescriptions in the USA alone in 2016.

Risperidone(Risperdal) – Originally marketed by J&J, it is among the most popularly prescribed antipsychotics in the USA and the World. There were about 4.0M prescriptions in the USA alone. While it doesn’t have the same magnitude of metabolic risks as olanzapine and quetiapine, it still triples the risk of type 2 diabetes within the first year of use. The lawsuits still came, and there were some expensive settlements.

Quetiapine(Seroquel) was the subject of over 10,000 lawsuits against AstraZeneca, eventually concluding a$198M class action in the USA over its diabetes-related side effects in 2010. There weresubsequent settlements that pushed the costs way up As an antipsychotic, quetiapine includes a distinct mechanism of action that may produce desirable features in some schizophrenics. Therefore, it remains a popularly prescribed medication - over 8.7M prescriptions in the USA alone in 2016!
[4]The valuation didn’t move with the recent, updated relacorilant results in Cushing’s syndrome. We think it is a relatively obvious signal for the ongoing phase 3 trial.

Original Article: No Surprises - Corcept Therapeutics - Q1-2019 Results

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