An Endocrine News roundup of the week’s pharmaceutical news, breakthroughs, and general information. *
Recordati Rare Diseases Announced New Data in Cushing’s Syndrome, Cushing’s Disease, and Post-Bariatric Hypoglycaemia at ENDO 2025
In April 2025, the FDA approved an expanded indication for ISTURISA® (osilodrostat) for the treatment of endogenous hypercortisolemia in adults with Cushing’s syndrome
Recordati Rare Diseases Inc. recently presented four poster presentations and one product theater featuring the company’s endocrinology portfolio at the Endocrine Society’s annual meeting, ENDO 2025, in San Francisco, Calif., including a presentation relating to the expanded indication of ISTURISA® (osilodrostat) for the treatment of endogenous hypercortisolemia in patients with Cushing’s syndrome.
After the ENDO 2025 gathering, Mohamed Ladha, President, general manager, North America, Recordati Rare Diseases, noted, “I am proud to shine a light on our recent contributions at ENDO 2025, where we showcased the transformative potential of our endocrinology portfolio and the work being done at Recordati for both ISTURISA® and SIGNIFOR®. The proof is these remarkable studies, their ongoing results, and what they can mean for endocrinologists and the patients in their care.”
In April, Recordati announced that the U.S. Food and Drug Administration (FDA) approved the supplemental new drug application (sNDA) for ISTURISA® (osilodrostat) for the treatment of endogenous hypercortisolemia in adults with Cushing’s syndrome for whom surgery is not an option or has not been curative. This is an expansion of the previous indication for the treatment of patients with Cushing’s disease, which is a sub-type of Cushing’s syndrome. The ISTURISA® indication expansion was supported by the ISTURISA® extensive clinical development program, which includes over 350 patients.
Milan Zdravkovic, executive vice president of Research & Development, Recordati, added, “At Recordati, we are thrilled to have presented several posters that show the true life-changing potential of our endocrinology portfolio, from the promising interim results of the LINC 6 study and LINC rollover study focused on ISTURISA® (osilodrostat) to a decade-long look at the safety of SIGNIFOR® (pasireotide) and its potential impact on post-bariatric hypoglycaemia as shown in the PASIPHY Phase II study.”
Key Data Presentations at ENDO 2025:
Irina Bancos, MD, from the Mayo Clinic presented promising interim results from the LINC 6 study, highlighting the long-term, real-world safety and effectiveness of osilodrostat in treating both pituitary and non-pituitary Cushing’s syndrome.
• Poster number: SUN-054; Abstract # 7820
• Over a 2-year period, osilodrostat was generally well tolerated, with adverse events mostly being mild or moderate in severity, leading to few discontinuations
• The data demonstrated that osilodrostat effectively manages various etiologies of Cushing’s syndrome, providing significant control over mean urinary free cortisol (mUFC) and late-night salivary cortisol (LNSC) levels
Richard Auchus, MD, PhD, from the University of Michigan presented encouraging findings from the LINC rollover study on the long-term safety and effectiveness of osilodrostat in patients with Cushing’s disease.
• Poster number: SUN-071; Abstract # 7892
• The study demonstrated that osilodrostat provides sustained clinical benefits, with the majority of patients continuing to experience positive outcomes by the end of the treatment period
• Importantly, the data reinforce existing evidence of the favorable safety profile of osilodrotat, highlighting its well-tolerated nature during extended use. The study reported low discontinuation rates due to treatment-related adverse events, and no new safety concerns were identified
Monica Gadelha, MD, PhD from the Universidade Federal do Rio de Janeiro presented the final results from a decade-long open-label Phase IV rollover study (B2412) on the long-term safety of pasireotide in patients with Cushing’s disease.
• Poster number: SUN-073; Abstract # 7838
• The study demonstrated that pasireotide is a well-tolerated treatment over the long term, with hyperglycaemia occurring infrequently
• Adverse events, including hyperglycaemia, were mostly manageable without necessitating treatment discontinuation, and no new safety signals were identified
Tracey McLaughlin, MD, MS, from Stanford Medicine introduced the PASIPHY Phase II study, which aims to evaluate the efficacy and safety of pasireotide in patients with post-bariatric hypoglycaemia (PBH).
• Poster number: SUN-562; Abstract # 7625
• This study is set to enroll approximately 72 adult patients across around 25 sites in Europe and the US
• The research will provide crucial data on the effectiveness and safety of pasireotide, helping to identify the optimal dose with the best benefit:risk ratio. The findings will determine the potential of pasireotide as a viable treatment option for individuals suffering from PBH
ENDO 2025 also included an interactive panel discussion as part of the product theater, hosted by Dr. Anthony Heaney, Dr. Elena Christofides, and Dr. Divya Yogi-Morren. The panel examined cortisol’s role in Cushing’s syndrome in a session titled, “Is Cortisol the Culprit?” with a focus on helping recognize the signs and symptoms of endogenous hypercortisolemia in patients with Cushing’s syndrome.
Amylyx Pharmaceuticals Presents New Exploratory Analyses from Phase 2 and Phase 2b Clinical Trials of Avexitide in Post-Bariatric Hypoglycemia at ENDO 2025
Amylyx Pharmaceuticals, Inc. announced the presentation of new exploratory analyses from the Phase 2 PREVENT and Phase 2b clinical trials of avexitide, an investigational, first-in-class glucagon-like peptide-1 (GLP-1) receptor antagonist for the treatment of post-bariatric hypoglycemia (PBH) at ENDO 2025.
In the Phase 2b trial, avexitide 90 mg once daily, the dose being evaluated in the pivotal Phase 3 LUCIDITY trial, led to a 64% least-squares (LS) mean reduction (p=0.0031) vs. baseline in the composite rate of Level 2 and Level 3 hypoglycemic events in PBH, with more than half of the participants experiencing no events during the treatment period. LUCIDITY is a multicenter, randomized, double-blind, placebo-controlled Phase 3 clinical trial evaluating the efficacy and safety of avexitide in approximately 75 participants with PBH following Roux-en-Y gastric bypass surgery. The FDA-agreed-upon primary endpoint of LUCIDITY is reduction in the composite of Level 2 and Level 3 hypoglycemic events. Consistent reductions in composite rate of Level 2 and Level 3 hypoglycemic events also were seen with avexitide 45 mg twice daily studied in the Phase 2b trial and avexitide 30 mg twice daily and 60 mg once daily studied in the Phase 2 PREVENT trial. New pharmacokinetic (PK) and pharmacodynamic (PD) data were also presented demonstrating continuous pharmacologic activity of the 90 mg once daily dose regimen for a 24-hour period.
“Post-bariatric hypoglycemia can profoundly disrupt daily life, requiring individuals to carefully manage meals, social interactions, and routines, often while living in fear of their next hypoglycemic event. The new analysis presented at ENDO 2025 continues to support that avexitide may significantly reduce the frequency of these events,” said Marilyn Tan, MD, FACE, principal investigator of the LUCIDITY trial and Clinical Associate Professor at Stanford University.
Camille L. Bedrosian, MD, chief medical officer of Amylyx, added, “Post-bariatric hypoglycemia is a serious and underrecognized condition with no FDA-approved treatments. The data presented show that, in an exploratory analysis from the Phase 2 PREVENT and Phase 2b clinical trials, avexitide significantly reduced the composite rate of Level 2 and 3 hypoglycemic events, including at the 90 mg once daily dose that is being studied in our pivotal Phase 3 LUCIDITY trial. We are particularly encouraged that over half of participants did not experience Level 2 or Level 3 hypoglycemic events during the treatment period. In addition, the pharmacokinetic and pharmacodynamic data demonstrated continuous pharmacologic activity of avexitide 90 mg once daily dose over 24 hours. We continue to be encouraged by avexitide’s potential to deliver consistent, meaningful benefit to people living with PBH.”
The population PK and PD analyses presented at ENDO 2025 demonstrated that avexitide 90 mg once daily maintained consistent GLP-1 receptor inhibition from morning to midnight and between doses. In vitro potency studies showed an IC₅₀ of approximately 20-30 nM (70-100 ng/mL), indicating robust target inhibition even in the presence of significant levels of GLP-1. PK modeling demonstrated that avexitide plasma levels exceeded IC₅₀ for a full 24-hour period.
LUCIDITY was informed by data from five PBH clinical trials of avexitide showing consistent, dose-dependent effects, including statistically significant and clinically meaningful reductions in hypoglycemic events. Avexitide was generally well-tolerated, with a favorable safety profile replicated across clinical trials. Completion of recruitment for LUCIDITY is expected in 2025, with a data readout anticipated in the first half of 2026 and, if approved, commercial launch anticipated in 2027.
Marea Therapeutics Presents Preclinical Data on Novel Growth Hormone Receptor Antagonist Antibody, MAR002, for the Treatment of Acromegaly at ENDO 2025
Marea Therapeutics, Inc., announced the presentation of preclinical data on MAR002, a novel growth hormone receptor (GHR) antagonist antibody for the treatment of acromegaly, at the ENDO 2025.
The oral presentation, titled “Development of a Novel Growth Hormone Receptor Antagonist Antibody for the Treatment of Acromegaly,” highlights the significant potential of MAR002 to address critical unmet needs in patients suffering from this rare and highly morbid disease.
Presentation highlights include:
- Highly potent GHR antagonism: MAR002 is a novel, highly potent antagonist of growth hormone (GH) signaling. It demonstrates superior GHR binding relative to pegvisomant and approximates the affinity of native GH.
- Allosteric mechanism of action: MAR002 does not prevent GH binding to the GHR in vitro and potently antagonizes downstream signaling across a broad range of GH concentrations.
- Superior suppression: MAR002 suppresses GHR signaling in vitro, achieving 93% suppression of human GHR compared to 24% for pegvisomant.
- Enhanced durability: MAR002 exhibited potent and sustained insulin-like growth factor-1 (IGF-1) suppression in vivo in non-human primates (NHPs). Compared head-to-head to pegvisomant, a single dose of MAR002 resulted in a similar maximum IGF-1 suppression, but with a considerably longer duration of effect.
Marea Therapeutics has completed a GLP-toxicology study to assess MAR002’s safety. The preclinical pharmacology data strongly support advancing MAR002 into clinical development; a Phase 1 first-in-human study is expected to begin in the third quarter of 2025. Marea’s development strategy aims for rapid advancement into acromegaly patients after achieving proof of mechanism in healthy volunteers, with a clear path to approval guided by FDA guidance for IGF-1 normalization.
“The preclinical data presented at ENDO 2025 underscore the potential of MAR002 to meaningfully transform the treatment landscape for acromegaly,” said Ethan Weiss, MD, chief scientific officer of Marea Therapeutics. “With its strong potency, enhanced durability, and favorable developability profile, MAR002 is uniquely positioned to overcome the limitations of current therapies and offer a more effective, targeted approach for patients. We are excited to advance MAR002 into clinical development and bring forward a next generation and potential best-in-class GHR antagonist.”
Marea Therapeutics believes MAR002 represents a significant opportunity to replace and expand the market for existing growth hormone receptor antagonists (GHRAs) and could also be used in combination with somatostatin receptor ligands (SRLs), offering a more effective and convenient treatment option for patients with acromegaly.
Corcept Submits New Drug Application for Relacorilant as a Treatment for Patients with Platinum-Resistant Ovarian Cancer
Corcept Therapeutics Incorporated, a commercial-stage company engaged in the discovery and development of medications to treat severe endocrinologic, oncologic, metabolic and neurologic disorders by modulating the effects of the hormone cortisol, has submitted a new drug application (NDA) to the U.S. Food and Drug Administration (FDA) for its proprietary, selective cortisol modulator, relacorilant, to treat patients with platinum-resistant ovarian cancer.
Corcept’s filing is based on positive data from its pivotal Phase 3 ROSELLA and Phase 2 trials. In these trials, patients who received relacorilant plus nab-paclitaxel experienced improved progression-free and overall survival compared to patients who received nab-paclitaxel monotherapy, with no need for biomarker selection. Relacorilant was well-tolerated, consistent with its known safety profile. Importantly, the type, frequency and severity of adverse events in the combination arms were similar to those in the nab-paclitaxel monotherapy arms. Relacorilant did not increase the safety burden of the patients who received it.
“This submission is an important milestone for Corcept as we now have two New Drug Applications before the FDA: Relacorilant in combination with nab-paclitaxel as a treatment for people with platinum-resistant ovarian cancer and relacorilant as a treatment for patients with hypercortisolism,” said Joseph K. Belanoff, MD, Corcept’s chief executive officer. “Better treatment options are needed for the many patients living with these diseases. Our oncology and endocrinology business units are already working to make sure relacorilant is available immediately following regulatory approval.”
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