Peptide News Digest

#Nejm

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Research · View digest

Rhythm Pharmaceuticals Announces New England Journal of Medicine Publication of Phase 3 TRANSCEND Trial Results for Setmelanotide (IMCIVREE, MC4R Agonist) in Acquired Hypothalamic Obesity on Wednesday July 8: Largest and Longest Placebo-Controlled Study Ever Conducted in the Condition, Reporting Weight and Hunger Improvements in Adults and Pediatric Patients Aged Four and Older Alongside Reductions Documented Against Placebo

Rhythm Pharmaceuticals announced Wednesday July 8, 2026 that Phase 3 TRANSCEND trial results for setmelanotide (IMCIVREE), a melanocortin-4 receptor (MC4R) agonist, in patients with acquired hypothalamic obesity have been published in the New England Journal of Medicine. TRANSCEND is the largest and longest placebo-controlled clinical trial ever conducted in acquired hypothalamic obesity, a rare and severe metabolic condition caused by damage to the hypothalamus from tumors, surgery, radiation, or trauma. The publication documents weight and hunger improvements in adult and pediatric patients aged four years and older across the treatment arm versus placebo control. IMCIVREE is already FDA-approved as a once-daily subcutaneous injection for chronic weight management in adults and pediatric patients aged four and older with acquired hypothalamic obesity, as well as for syndromic or monogenic obesity in patients with confirmed loss-of-function variants. The NEJM publication follows the earlier Kalohexis confidential IPO filing (July 7-8) on the dual MC3R/MC4R melanocortin platform, sustaining momentum around melanocortin biology as the highest-profile non-GLP-1 obesity mechanism in commercial development.

Clinical Trials · View digest

Boehringer Ingelheim Survodutide Full 48-Week Phase 2 MASH Data in NEJM (EASL 2026): GLP-1/Glucagon Dual Agonist Drives MASH Improvement Without Fibrosis Worsening in 47-62% vs 14% Placebo

Boehringer Ingelheim's survodutide full 48-week Phase 2 MASH dataset published in the New England Journal of Medicine alongside the EASL 2026 presentation. MASH improvement without worsening of fibrosis occurred in 47% of the 2.4 mg group, 62% of the 4.8 mg group, and 43% of the 6.0 mg group, versus 14% on placebo. Up to 52% of survodutide-treated adults achieved significant improvement across fibrosis stages F1, F2, and F3 versus around 26% on placebo. Survodutide is an investigational long-acting glucagon/GLP-1 receptor dual agonist (BI 456906, partnered with Zealand Pharma) for once-weekly subcutaneous administration. The Phase 3 program is advancing through LIVERAGE (~1,800 adults with MASH F2-F3) and LIVERAGE-Cirrhosis (~1,590 adults with compensated MASH cirrhosis F4). Survodutide also posted 16.6% weight loss in the SYNCHRONIZE-1 obesity Phase 3 (April 2026). The NEJM publication is the strongest peer-reviewed validation of the GLP-1/glucagon dual mechanism in MASH to date.

Clinical Trials · View digest

Daraxonrasib NEJM Publication (May 2026): Revolution Medicines' RAS(ON) Inhibitor Hit 35% ORR + 13.1-Month OS in RAS G12-Mutated Pancreatic Cancer Phase 1/2

The New England Journal of Medicine published Revolution Medicines' daraxonrasib (RMC-6236) Phase 1/2 data in previously treated advanced RAS-mutated pancreatic adenocarcinoma in May 2026. In the subgroup of 26 patients with G12 mutations treated at the 300 mg dose, objective response rate hit 35% with median progression-free survival 8.5 months and median overall survival 13.1 months — outcomes meaningfully better than the historical 5-month median OS in second-line PDAC. The mechanism is unusual: daraxonrasib is an oral small molecule that acts as a molecular glue, recruiting the peptidyl-prolyl isomerase cyclophilin A to form a tri-complex with active GTP-bound mutant RAS, blocking effector binding and downstream signaling. The drug targets KRAS, HRAS, and NRAS in the on-state — a mechanistically distinct approach from Chugai's LUNA18 cyclic peptide RAS inhibitor. FDA granted Expanded Access. The cyclophilin A-mediated mechanism puts peptidyl-prolyl chemistry at the center of a major oncology readout.