What's next in endocrinology — October 20, 2026

This edition covers four pending regulatory decisions between now and the end of December 2026: relacorilant in Cushing's syndrome and CagriSema in obesity, in the United States, and oral orforglipron and navepegritide in achondroplasia, in the European Union. Only relacorilant has a published target date; the others are company or European-procedure estimates and are labeled as such.

1. Relacorilant in endogenous hypercortisolism (Cushing's syndrome)

[Pending regulatory decision] [United States] [Confirmed date: December 17, 2026 (PDUFA target date, per Corcept)]
What it is: An oral selective glucocorticoid receptor modulator without antiprogestogenic activity. Corcept resubmitted the application in June 2026 after a complete response letter (announced December 31, 2025) in which the FDA, while acknowledging that GRACE met its primary endpoint, could not reach a favorable benefit-risk assessment without more evidence; the resubmission includes additional analyses requested by the agency. In GRACE (phase 3; n = 152 with Cushing's and hypertension, hyperglycemia or both), after 22 open-label weeks, the 12-week double-blind randomized-withdrawal phase showed less loss of blood pressure control with relacorilant than with placebo (OR 0.17; 95% CI 0.04–0.77; p = 0.02).
What problem it solves: When surgery fails or is not possible, current options are osilodrostat, metyrapone, ketoconazole or levoketoconazole, pasireotide or mifepristone; the latter causes hypokalemia and endometrial thickening through its antiprogestogenic effect, which relacorilant aims to avoid.
Critical take: The primary endpoint is maintenance of blood pressure, a surrogate, in a manufacturer-funded trial; the FDA has already turned it down once on the same trials, so a second rejection is possible.
https://ir.corcept.com/news-releases/news-release-details/corcept-therapeutics-announces-second-quarter-financial-4
https://ir.corcept.com/news-releases/news-release-details/corcept-receives-complete-response-letter-relacorilant-treatment
https://www.businesswire.com/news/home/20260527119062/en/Corcept-to-Resubmit-its-New-Drug-Application-for-Relacorilant-as-a-Treatment-for-Patients-with-Cushings-Syndrome
https://ir.corcept.com/news-releases/news-release-details/corcept-resubmits-new-drug-application-relacorilant-treatment
https://www.endocrine-abstracts.org/ea/0110/ea0110p69

2. CagriSema (weekly cagrilintide + semaglutide) in obesity

[Pending regulatory decision] [United States] [Estimated date: fourth quarter of 2026, per Novo Nordisk]
What it is: A weekly fixed combination of an amylin analogue and semaglutide 2.4 mg; submitted to the FDA on December 18, 2025. Novo Nordisk has not published a PDUFA date and, at its Capital Markets Day on September 21, 2026, placed the decision in the fourth quarter of 2026. In REDEFINE 1 (NEJM; n = 3,417 without diabetes, 68 weeks) weight loss was 20.4% versus 3.0% with placebo; in REDEFINE 2 (NEJM; n = 1,206 with type 2 diabetes, 68 weeks) it was 13.7% versus 3.4% (both figures, treatment-policy estimand).
What problem it solves: It seeks greater weight loss than semaglutide alone by adding amylin-mediated satiety; tirzepatide is currently the efficacy benchmark.
Critical take: In REDEFINE 4, open-label against tirzepatide 15 mg (n = 809, 84 weeks), it failed to show non-inferiority (20.2% versus 23.6%, treatment-regimen estimand); there are no cardiovascular outcome data yet and all trials are manufacturer-sponsored.
https://www.novonordisk.com/content/dam/nncorp/global/en/investors/pdfs/capital-markets-day/2026/obesity-presentation-cmd-2026.pdf
https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=916470
https://www.novonordisk.com/news-and-media/news-and-ir-materials/news-details.html?id=916501
https://www.nejm.org/doi/full/10.1056/NEJMoa2502081
https://www.nejm.org/doi/abs/10.1056/NEJMoa2502082

3. Oral orforglipron (Foundayo) in obesity and type 2 diabetes in Europe

[Pending regulatory decision] [European Union] [Estimated date: December 2026, per the usual European Commission timeline after the positive CHMP opinion at its October 12–15, 2026 meeting]
What it is: An oral, non-peptide GLP-1 receptor agonist taken once daily, with or without food. The CHMP recommended authorization for weight management (BMI ≥30, or ≥27 with at least one comorbidity) and for type 2 diabetes. According to the EMA, in two weight trials (more than 4,740 adults, 72 weeks) weight loss was about 5% to 11% depending on dose versus about 2% to 2.5% with placebo; in four diabetes trials (3,765 adults) HbA1c fell by 1.2 to 1.9 points, versus 0.8 with dapagliflozin and 1.2 to 1.5 with oral semaglutide 7 and 14 mg.
What problem it solves: It offers an oral GLP-1 without the fasting-administration rules of oral semaglutide and, unlike injectables, without a cold chain, for patients who refuse or cannot access injectables.
Critical take: In indirect comparison, weight loss is lower than reported with injectable semaglutide or tirzepatide. Its published cardiovascular trial, ACHIEVE-4 (The Lancet, September 30, 2026; open-label; n = 2,749 with type 2 diabetes and elevated cardiovascular risk), showed non-inferiority versus insulin glargine (4-component MACE: HR 0.84; 95% CI 0.59–1.20), but there are no cardiovascular outcome data in obesity without diabetes. The trials are Lilly's, and access will depend on price and national reimbursement.
https://www.ema.europa.eu/en/news/new-oral-glp-1-medicine-weight-management-type-2-diabetes
https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-12-15-october-2026
https://investor.lilly.com/node/54996/pdf

4. Weekly navepegritide (Yuviwel) in achondroplasia

[Pending regulatory decision] [European Union] [Estimated date: fourth quarter of 2026, per Ascendis Pharma]
What it is: A sustained-release prodrug of C-type natriuretic peptide given as a weekly injection, with a positive CHMP opinion at its October 12–15, 2026 meeting for children two years of age and older whose epiphyses are not closed; in the United States the FDA approved it under the accelerated approval pathway (announced February 27, 2026). In ApproaCH (phase 2b, double-blind; n = 84 randomized, ages 2 to 11, 52 weeks, 2:1 versus placebo) annualized growth velocity was 5.89 versus 4.41 cm/year (difference 1.49 cm/year; 95% CI 1.05–1.93).
What problem it solves: The alternative authorized in Europe, vosoritide, requires a daily injection; a weekly schedule reduces the burden on children and families.
Critical take: Growth velocity is a surrogate; there are no data yet on final height or complications (foramen magnum stenosis, apnea, surgeries), and the trial was run by the manufacturer, Ascendis.
https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-12-15-october-2026
https://doi.org/10.1001/jamapediatrics.2025.4771
https://investors.ascendispharma.com/news-releases/news-release-details/once-weekly-transconr-cnp-navepegritide-receives-positive-chmp
https://investors.ascendispharma.com/news-releases/news-release-details/fda-approves-once-weekly-yuviwelr-navepegritide-children

*What's next in endocrinology — October 20, 2026*

1. Relacorilant in Cushing's syndrome: FDA decides on Dec 17, 2026, after an earlier rejection.
2. CagriSema in obesity: FDA decision expected in Q4 2026, per Novo Nordisk.
3. Oral orforglipron (Foundayo) in obesity and T2D: European Commission decision expected in December 2026 after a positive CHMP opinion.
4. Weekly navepegritide in achondroplasia: European Commission decision expected in Q4 2026, per Ascendis.

With a critical take on each item and official sources.
Full text and audio: https://boletinesmedicos.com/en/endocrinology/2026-10-20-viene.html
MedBulletins · boletinesmedicos.com

What's next in endocrinology (October – December 2026), with dates taken from official sources:

• December 17, 2026: FDA decision on relacorilant in endogenous hypercortisolism, after a complete response letter.
• Fourth quarter of 2026 (Novo Nordisk estimate): FDA decision on CagriSema in obesity, which failed non-inferiority against tirzepatide.
• December 2026 (usual European Commission timeline): oral orforglipron in obesity and type 2 diabetes.
• Fourth quarter of 2026 (Ascendis estimate): weekly navepegritide in achondroplasia.

Each item covers the problem it addresses, current practice and a critical take (sponsorship, surrogate endpoints, access in our setting).

Full text and audio: https://boletinesmedicos.com/en/endocrinology/2026-10-20-viene.html

#Endocrinology #Obesity #Diabetes #CushingSyndrome #BoletinesMedicos

What's next in endocrinology: FDA rules on relacorilant in Cushing's (Dec 17) and CagriSema (Q4 2026); the EU on oral orforglipron and navepegritide in achondroplasia. Critical take: https://boletinesmedicos.com/en/endocrinology/2026-10-20-viene.html