Biomedicine Weekly · Week 40, 2026 · 09.28 — 10.04

On this pageRetatrutide produced mean weight reductions of 17.6%, 23.7% and 25.0% at 4, 9 and 12 mg over 80 weeks in 2339 adults without diabetes, versus 3.9% on placebo, with WOMAC pain and apnea-hypopnea improvements in osteoarthritis and sleep apnea subgroups. In TRIUMPH-2, 47% of diabetic patients on 12 mg lost at least 20% of body weight and 72% reached HbA1c of 6.5% or lower. Orforglipron proved non-inferior to insulin glargine on MACE-4 with less hypoglycemia, and survodutide cut weight 8.2-9.8% in type 2 diabetes. Gastrointestinal adverse events were the common thread.

NN Engl J Med10.01

Retatrutide, a Triple Hormone Receptor Agonist, for Treatment of Obesity.

Once-weekly retatrutide produced mean body-weight reductions of 17.6%, 23.7%, and 25.0% at 4, 9, and 12 mg over 80 weeks in 2339 adults with obesity without diabetes, versus 3.9% with placebo. In subgroups, WOMAC pain fell 3.5 and 3.6 points at 9 and 12 mg versus 1.9 with placebo in 574 participants with knee osteoarthritis, and apnea-hypopnea events per hour fell 34.3 and 31.7 versus 9.9 in 243 participants with obstructive sleep apnea. The phase 3 results extend triple-receptor agonist efficacy beyond weight to obesity-related pain and sleep outcomes.

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Rreddit.com10.03

Phase 3 results for Retatrutide

Retatrutide produced mean weight losses of 17.6% at 4 mg, 23.7% at 9 mg and 25.0% at 12 mg over 80 weeks in 2339 randomized patients with obesity but without diabetes, versus 3.9% with placebo (P<0.001). Subgroups with knee osteoarthritis saw pain scores fall by 3.2 to 3.6 versus 1.9 on placebo, and patients with obstructive sleep apnea had 22.9 to 34.3 fewer events per hour versus 9.9. The most common adverse events were gastrointestinal.

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medicalxpress.com10.01

New triple agonist drug produces substantial weight loss in diabetic patients

Retatrutide, a triple agonist of the GIP, GLP-1 and glucagon receptors, produced substantial weight loss and improved blood sugar control in adults with overweight or obesity and type 2 diabetes in the phase 3 TRIUMPH-2 trial of 1152 participants over 80 weeks. At the 12 mg dose, 47% lost at least 20% of their starting weight and 72% achieved an HbA1c of 6.5% or lower, compared with 6% and 29% with placebo. Gastrointestinal adverse events, including diarrhoea and nausea, were more common with retatrutide than placebo.

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LLancet10.01

Cardiovascular safety of orforglipron versus insulin glargine in adults with type 2 diabetes at increased cardiovascular risk (ACHIEVE-4): a phase 3, event-driven, randomised, open-label, non-inferiority, active comparator trial.

Orforglipron, an oral non-peptide GLP-1 receptor agonist, was non-inferior to insulin glargine for four-component major adverse cardiovascular events in 2749 adults with type 2 diabetes at increased cardiovascular risk: MACE-4 occurred in 57 (4·2%) of 1358 orforglipron participants versus 67 (5·0%) of 1343 insulin glargine participants (HR 0·84; 95% CI 0·59-1·20) over a median follow-up of 2 years. Clinically significant or severe hypoglycaemia was less frequent with orforglipron (93, 6·8%) than insulin glargine (260, 19·2%), while gastrointestinal adverse events were more frequent (62·1% vs 14·2%). The results establish cardiovascular safety for a non-peptide GLP-1 receptor agonist, a class not previously studied for this outcome.

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NN Engl J Med10.01

Survodutide Once Weekly in Adults with Obesity and Type 2 Diabetes.

Once-weekly survodutide, a glucagon receptor-GLP-1 receptor dual agonist, produced mean weight reductions of 8.2% at 3.6 mg and 9.8% at 6.0 mg over 76 weeks in 752 adults with type 2 diabetes and BMI of 27 or more, versus 3.9% with placebo. At least 5% weight loss occurred in 57.6% and 64.5% of the survodutide groups versus 35.1% on placebo, with glycated hemoglobin falling 0.9 and 0.8 percentage points. Gastrointestinal adverse events, mostly mild to moderate, occurred in 72.8% and 77.7% of survodutide recipients.

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On this pageDizhe Pharmaceutical granted AstraZeneca worldwide rights to Shuwozhe for $600 million upfront plus up to $900 million in milestones and tiered royalties rising to the low double digits, a record upfront for a single Chinese small molecule, received on September 29. Novartis licensed Abogen's mRNA-encoded CD19xCD3 T cell engager ABO2203 for $575 million up front with $7.2 billion in potential milestones. Merck licensed Sipurei's KRAS G12D(ON) inhibitor SPR2015 for $400 million upfront in a deal worth up to $2.13 billion, with an IND now filed. AstraZeneca also invested $2 billion for about 12% of Summit Therapeutics alongside an Ivonescimab clinical collaboration.

On this pageThe FDA approved iberdomide for multiple myeloma based on minimal residual disease negativity, the first approval for the disease on that endpoint; China's NMPA followed with conditional approval on September 30, making it the first approved Cereblon E3 ubiquitin ligase modulator worldwide. FDA also approved Eli Lilly's pirtobrutinib on October 2 for previously untreated CLL or SLL without 17p deletion, after BRUIN CLL-313 showed median PFS not estimable versus 33.5 months with bendamustine-rituximab (HR 0.20). AbbVie's JUVMO (tavapadon), the first selective D1/D5 receptor agonist, was approved for Parkinson's disease.

On this pageAt ASTRO, the phase 3 SWOG S1827 MAVERICK trial found MRI surveillance alone beat prophylactic cranial irradiation plus MRI on cognitive failure-free survival in small-cell lung cancer (p=0.001). The evERA study showed giredestrant plus everolimus raised median PFS from 5.5 to 8.8 months in ER-positive, HER2-negative advanced breast cancer, reaching 10 months with a 63% risk reduction in ESR1-mutant tumors. Weekly oral islatravir-lenacapavir matched daily triple therapy for HIV suppression at week 48 in 607 adults. The VIRAGE phase 2b trial extended overall survival for intravenous oncolytic virus VCN-01 with chemotherapy in metastatic pancreatic cancer.

Tthelancet.com10.02

[News] 2026 ASTRO Annual Meeting

MRI surveillance alone beat prophylactic cranial irradiation plus MRI on cognitive failure-free survival in the phase 3 SWOG S1827 MAVERICK trial. In 304 patients with limited and extensive-stage small-cell lung cancer who had completed initial therapy, MRI-only monitoring improved the primary endpoint (HR 0·60, 90% CI 0·46–0·78; p=0·001) at a median follow-up of 22 months. The result challenges routine prophylactic cranial irradiation, long tied to better survival but more neurological toxicity.

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medicalxpress.com10.01

Novel treatment combination improves progression-free survival in most common form of metastatic breast cancer

Adding the oral SERD giredestrant to everolimus improved progression-free survival in ER-positive, HER-2-negative advanced breast cancer after prior CDK 4/6 inhibitor treatment. In the phase 3 evERA study of 373 patients, median PFS rose from 5.5 to 8.8 months overall (44% risk reduction) and from 5.5 to 10 months in the roughly 55% with ESR1-mutant tumors (63% risk reduction). It offers an all-oral option where post-CDK 4/6 choices are limited.

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NN Engl J Med10.03

Phase 3 Trial of Weekly Oral Islatravir-Lenacapavir for HIV-1 Treatment.

Once-weekly oral islatravir-lenacapavir maintained viral suppression as well as once-daily bictegravir-emtricitabine-tenofovir alafenamide in a phase 3 trial of 607 adults with virologically suppressed HIV-1. At week 48, HIV-1 RNA of 50 copies per milliliter or higher was reported in no ISL/LEN participants and 1 (0.3%) on B/F/TAF, meeting a 4-percentage-point noninferiority margin. The finding supports a long-acting weekly oral option for suppressed patients.

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Nnature.com09.30

Intravenous hyaluronidase-expressing oncolytic adenovirus with chemotherapy in metastatic pancreatic cancer: a randomized phase 2b trial

Intravenous zabilugene almadenorepvec (VCN-01), a hyaluronidase-expressing oncolytic adenovirus, plus gemcitabine and nab-paclitaxel prolonged overall survival over chemotherapy alone in the randomized phase 2b VIRAGE trial in treatment-naive metastatic pancreatic cancer. The finding supports adding an oncolytic virus to standard first-line chemotherapy in this setting.

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On this pageTwo Nature papers map antibody diversification, showing MLLT1/MLLT3 histone readers and NELF-mediated polymerase pausing concentrate AID at target loci. Loss of p53 was shown to reorganize Wnt signaling into a radial gradient enabling mutant clonal expansion. A population-scale immune multiome atlas of 10 million nuclei from 1,108 Finns yielded 593,765 peak-gene links and testable hypotheses for over half of immune disease associations. The Genome in a Bottle HG002 v5.0q benchmark adds 200 Mbp of callable sequence and triples structural variant detection. TWISTAR deorphanization revealed shared immune dominant tumor antigens, and the uRARE-seq urine RNA test detected 95% of localized bladder cancers, outperforming cytology.

NNature10.02

Histone readers MLLT1 and MLLT3 concentrate AID to confer locus specificity.

The super elongation complex histone readers MLLT1 and MLLT3 prove to be determinants of selective AID activity in antibody diversification. Combined loss of the two readers abolishes all AID-dependent mutagenic processes, recapitulating AID deficiency, while transcriptional changes after deletion are modest. The readers locally enrich AID downstream from promoters, with MLLT1 acting dominantly in mice through condensate formation, and fusing AID to either reader restores class-switch recombination and mutagenesis in double-knockout cells.

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NNature10.01

Transcription pause and elongation regulators mediate somatic hypermutation.

Somatic hypermutation requires the transcription pause regulator NELF plus the super elongation complex components MLLT1 and MLLT3 and the INT-PP2A phosphatase module. NELF associates with RNA polymerase II in the AID target window, and without NELF, AID still reaches chromatin and PolII still transcribes, but cytosine deamination fails. MLLT1 and MLLT3 bind AID through their YEATS domain and are needed to enrich AID at its target sites, assigning NELF-PolII pausing in gene bodies a role in generating the AID substrate.

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medicalxpress.com10.01

How loss of the critical tumor suppressor p53 enables mutant cells to expand through normal tissue

Loss of p53 lets mutant clones expand through normal tissue by reorganizing Wnt signaling into a persistent radial gradient, low at the clone edge and high at its center, rather than by simply raising overall Wnt activity. In mouse skin, clones with this gradient expanded efficiently while clones with uniformly higher Wnt activity expanded less. The work maps how p53, acting through Sfrp1, Lrp1 and Usp22, shifts epidermal progenitor cells toward self-renewal and away from differentiation, enabling clonal expansion long before tumors form.

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NNature10.02

Population-scale immune multiome atlas reveals regulatory disease mechanisms.

Simultaneous single-nucleus profiling of chromatin accessibility and gene expression in 10 million peripheral blood mononuclear cells from 1,108 Finnish individuals yields 51,083 cis-expression QTLs, 338,100 cis-chromatin accessibility QTLs and 593,765 peak-gene links. Variants completing chromatin-to-expression cascades show twice the disease colocalization of chromatin-only effects, and massively parallel reporter assays validate 10,428 fine-mapped QTLs. The atlas supplies testable hypotheses for over half of immune disease associations and explains why disease variants preferentially target evolutionarily constrained genes through regulatory buffering at the chromatin-to-expression interface.

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Bbiorxiv.org10.01

The Genome In A Bottle HG002 assembly-based variant benchmark set enables comprehensive benchmarking of small and structural variants.

The Genome in a Bottle Consortium's HG002 v5.0q benchmark set, built from a fully phased, highly curated diploid assembly, delivers confident small- and structural-variant calls in previously inaccessible regions such as segmental duplications, tandem repeats, homopolymers, and complex immune loci. Relative to v4.2.1 it adds 200 Mbp of callable sequence, increases variant detection by 18% for small variants and 3-fold for structural variants, and is available for GRCh37, GRCh38, and CHM13.

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Bbiorxiv.org09.29

Functional Deorphanization of Tumor-reactive TCRs Uncovers a Landscape of Shared, Immune Dominant Antigens across Cancers

The TWISTAR platform deorphanizes single-cell-derived TCRs against tumor transcriptomes and directly validates TCR engagement, so it recovers only functionally immunogenic antigens. Applied to melanoma, breast, and hepatocellular carcinoma patients responding to immune checkpoint blockade, it shows tumor-reactive TCRs recognize many targets beyond neoantigens, including peptides from unannotated coding sequences and novel transcripts. Many antigens are shared across patients and cancer types, with multiple T cell clones converging on a few immune dominant epitopes, supporting pan-cancer vaccine development.

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medicalxpress.com10.02

RNA urine test outperforms standard bladder cancer tests and could help guide treatment

A urine RNA test called uRARE-seq identified 95% of people with localized bladder cancer and correctly classified 90% of those without it, outperforming standard urine cytology and a DNA-based urine test in a study of 683 urine samples. The test detects cell-free RNA fragments rather than DNA mutations, tracks tumor biology including low- versus high-grade disease, and identified residual disease after surgery and BCG immunotherapy. A derived biomarker predicted whether tumors were more likely to respond to immunotherapy or chemotherapy.

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