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Updated Phase 2 Results: Relacoriant & Cushing's Syndrome

11:10 EDT 29 Apr 2019 | Biotech Watcher

Corcept Therapeutics (CORT) investigators presented posters at the recent Annual Meeting of the American Association of Clinical Endocrinologists (AACE) in late April 2019.


We wanted to make an immediate summary of one presentation in particular: the updated results from the recent Phase 1/2 of relacorilant to treat Cushing’s syndrome. A summary of the other AACE presentations can be posted later.

Quick Summary


The data for this article comes from two different clinical trials to treat Cushing’s syndrome:
The registration trial (SEISMIC) that led to Korlym’s FDA approval; and
The AACE Presentation of the Phase 1/2, dose-ranging trial of relacorilant.

Main Efficacy Endpoints


Compared to our last write-up, the responder analysis makes a stronger argument for a dose-response.

High-dose Relacorilant vs. Korlym
Cushing’s Syndrome Treatment
Responder Analysis from Last Observation
Updated from AACE Conference
April 27, 2019
High-Dose Relacorilant[1]
Phase 1/2a

Low-Dose Relacorilant
Phase 1/2a
N=17
Korlym
SEISMIC Trial
N=50
Glucose Control ↑
BP Reduction
Glucose Control ↑
BP Reduction
Glucose Control ↑
BP Reduction
6/12
50%
7/11
63.6%
2/13
15.4%
5/12
41.7%

60%

38.1%

In the early data, the low-dose group appeared best for improving glucose tolerance. With the updated AACE results, we see that the trends strongly favor high-dose over low-dose relacorilant. With the small samples, relacorilant may be showing better responses for blood pressure reduction. Furthermore, hypertensive episodes may occur with Korlym but appear to be absent with relacorilant.

If upheld in the GRACE pivotal trial, the hypertension results strengthen the rationale for relacorilant being viewed as a superior drug.

Other Endpoints


42.9% (15/35) of patients lost weight. 35.3% (6/17) of low-dose patients lost weight (mean loss = 2.2 kg) versus 60% (9/15) of high-dose patients (mean loss = 5.1 kg). This is a strong contrast.

Furthermore, there were (very) statistically significant improvements in:

Cognitive Functioning (Trail-making tests)
Depression (Beck Depression Inventory)
Liver Inflammation (ALT, AST)
Hypercoagulopathy[2](Platelet Count, Factor VIII)
Quality of Life

Overall, this is excellent data.

There were some mild to moderate increases in dose-related, adverse events. This may reflect the body response to an abrupt withdrawal of cortisol. In the current GRACE pivotal trial, the patients are given a milder introduction to relacorilant, which will hopefully be reflected in improved safety data.

Nevertheless, if this overall safety is replicated, we don’t see a barrier to approvability.

Our Thoughts

The updated results present a stronger case for relacorilant. The dose-response trends are strengthened. While we like the hypertension data, we are tempered by the small sample size. Nevertheless, the odds for success in the ongoing registration trial have increased.

The other AACE presentations look promising, especially the pilot analysis of the prevalence of hypercortisolism in type 2 diabetes with adrenal tumors.[3] There is a markedly high prevalence and if these results are confirmed, then this has relevant diagnostic and treatment implications.

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

This blog post is from The Biotech Watcher:
And about us, see http://alanhobbes.blogspot.com/2014/12/welcome-to-my-personal-thoughts-about.html

[1]The updated results will be presented in late April 2019. Pivonello R., et al. (2019) Efficacy and Safety of the Selective Glucocorticoid Receptor Modulator, Relacorilant (up to 400 mg/day), in Patients with Endogenous Hypercortisolism: Results from an Open-Label Phase 2 Study.Poster presented at the Annual Congress of American Association of Clinical Endocrinologists on April 27, 2019.
[2][2]Cushing’s patients have problems with excess coagulability
[3]Sachmechi I., et al. (April 25, 2019) Prevalence of Hypercortisolism in Patients with Type 2 Diabetes Mellitus with Incidentally Found Adrenal Adenomas: An Interim Analysis. Poster presented at the Annual Congress of American Association of Clinical Endocrinologists.

Original Article: Updated Phase 2 Results: Relacoriant & Cushing's Syndrome

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