Biomedicine Monthly · 2026 Sep
CBA FRONTIER INSIGHTS
This issue's figures
Open a card for the chart; click again to closeIvonescimab Outsurvives Pembrolizumab; RAS Finally Yields a First Approved Drug
September's defining moment came at the World Conference on Lung Cancer, where Akeso's PD-1/VEGF bispecific ivonescimab became the first therapy to beat pembrolizumab head-to-head on overall survival in a phase 3 trial, reaching a median of 30.8 months versus 22.6 months in first-line PD-L1-positive advanced NSCLC. Days earlier, the FDA approved Revolution Medicines' daraxonrasib, the first direct RAS-targeted oral drug, for metastatic pancreatic cancer, 44 years after RAS was identified as the first human oncogene. Regulators also greenlit first-ever treatments for Sanfilippo syndrome type A and Alexander disease, plus a once-weekly basal insulin. Meanwhile, Novartis's pelacarsen missed its cardiovascular endpoint, forcing a rethink of Lp(a) lowering, and xenotransplantation and gene-editing programs posted durable milestones.
Ivonescimab's Historic Survival Win
On this pageAt the World Conference on Lung Cancer, Akeso and Summit Therapeutics reported that ivonescimab, a PD-1/VEGF bispecific, beat pembrolizumab head-to-head on overall survival in the phase 3 HARMONi-2 trial in first-line PD-L1-positive advanced NSCLC: median OS of 30.8 versus 22.6 months, HR 0.73, P=0.009, a 27% reduction in death risk, with 234 OS events at 36-month follow-up. Benefit was strongest in PD-L1-high (HR=0.58) and squamous (HR=0.65) patients. It is the first drug to top pembrolizumab on both PFS and OS in a randomized phase 3 trial; a regulatory decision point arrives in November.
Ivonescimab Beats Keytruda on Overall Survival in Phase III HARMONi-2 NSCLC Trial
Ivonescimab, a PD-1/VEGF bispecific antibody, beat Merck's Keytruda on overall survival in the HARMONi-2 study, a phase III head-to-head trial in advanced NSCLC, with median OS of 30.8 months versus 22.6 months and a 27% reduction in relative risk of death. This is the first time a PD-1/VEGF bispecific has defeated Keytruda on overall survival in a phase III head-to-head trial. Akeso and Summit Therapeutics presented the data at the World Conference on Lung Cancer.
Ivonescimab Beats Pembrolizumab on Overall Survival in HARMONi-2 Trial
Ivonescimab, Akesu Bio's PD-1/VEGF bispecific antibody, beat pembrolizumab as first-line monotherapy in PD-L1-positive non-small cell lung cancer in the HARMONi-2 trial. Median overall survival was 30.8 months versus 22.6 months with pembrolizumab, HR=0.73, P=0.009, presented by Professor Zhou Caicun at the WCLC presidential symposium. It is the first drug to beat pembrolizumab in a randomized controlled trial on two endpoints.
Ivonescimab Beats Pembrolizumab on Overall Survival in PD-L1-Positive NSCLC in HARMONi-2
Ivonescimab monotherapy as first-line treatment for PD-L1-positive non-small cell lung cancer achieved a median overall survival of more than 30 months, extending survival by over 8 months compared with pembrolizumab. The phase 3 HARMONi-2 trial, led by Professor Zhou Caicun of Shanghai East Hospital and presented at the 2026 World Conference on Lung Cancer, is the first randomized double-blind phase 3 trial to show positive results for both overall survival and progression-free survival against pembrolizumab.
Ivonescimab Beats Pembrolizumab on Overall Survival in HARMONi-2, Head to Head
Ivonescimab from Akeso became the first therapy to beat pembrolizumab head to head on overall survival in a randomized phase 3 trial, with median OS of 30.8 months versus 22.6 months and a 27% reduction in death risk in HARMONi-2. Benefit concentrated in PD-L1-high (HR=0.58) and squamous (HR=0.65) patients. The same WCLC also featured two Chinese B7-H3 ADCs, HS-20093 and YL201, each cutting death risk 54% versus topotecan in relapsed small cell lung cancer.
Ivonescimab Beats Pembrolizumab on Overall Survival in HARMONi-2 Phase 3 Trial
Ivonescimab, a PD-1/VEGF bispecific antibody from Akeso, has delivered full overall survival results from the phase 3 HARMONi-2 trial, with a median OS of 30.8 months versus 22.6 months for pembrolizumab monotherapy in a head-to-head comparison. Reported by Caicun Zhou of Shanghai East Hospital, this makes ivonescimab the first cancer immunotherapy to achieve positive results in both progression-free survival and overall survival against pembrolizumab in a randomized, double-blind phase 3 study. A key regulatory decision point arrives in November.
Ivonescimab Beats Pembrolizumab on Overall Survival in Frontline PD-L1-Positive Advanced NSCLC
Ivonescimab extended median overall survival to 30.8 months versus 22.6 months for pembrolizumab in first-line treatment of PD-L1-positive (TPS ≥1%) advanced non-small cell lung cancer, cutting the risk of death by 27%. Data presented by Caicun Zhou of Shanghai East Hospital at the 2024 WCLC make ivonescimab the first drug to beat pembrolizumab head-to-head in a phase 3 trial with positive results on both progression-free and overall survival.
Ivonescimab Beats Pembrolizumab on Overall Survival in First-Line PD-L1-Positive Advanced NSCLC
Ivonescimab significantly extended overall survival versus pembrolizumab as first-line treatment for PD-L1-positive advanced NSCLC, meeting the prespecified statistical bar for significance. At a median follow-up of 36 months as of August 20, 2026, 234 overall survival events had occurred and median overall survival reached 30.8 months. Prespecified subgroup analyses showed a consistent survival benefit, most pronounced in patients with high PD-L1 expression.
First RAS-Targeted Drug Approved
On this pageOn August 26, 2026, the FDA approved Revolution Medicines' RASONQUE (daraxonrasib, formerly RMC-6236), a once-daily oral RAS(ON) multi-selective inhibitor, for adults with metastatic pancreatic ductal adenocarcinoma after at least one prior systemic therapy or unsuited to multi-drug combinations. It is the first approved drug to directly target the active-state RAS(ON) protein family and the first RAS-targeted therapy for metastatic PDAC, a disease where over 90% of patients carry KRAS mutations. The approval came about 6.5 months ahead of the FDA target date, 44 years after RAS was identified as the first human oncogene in 1982.
FDA Approves Revolution's RAS(ON) Inhibitor Daraxonrasib for Metastatic Pancreatic Cancer
The FDA approved Revolution's RASONQUE (daraxonrasib), a once-daily oral tablet, for adults with metastatic pancreatic ductal adenocarcinoma who have received at least one prior systemic therapy or are not candidates for multi-drug combination systemic therapy. The approval on 26 August 2026 came about 6.5 months ahead of the original FDA target date. Daraxonrasib is the first approved RAS(ON) multi-selective inhibitor and the first RAS-targeted drug for metastatic PDAC that broadly inhibits multiple RAS mutations.
FDA Approves Revolution Medicines' RASONQUE (daraxonrasib) for Metastatic Pancreatic Cancer
The FDA approved Revolution Medicines' RASONQUE (daraxonrasib) on August 26 for metastatic pancreatic cancer. It is the first approved drug worldwide to directly target RAS. The approval marks a first for the RAS-targeting class in pancreatic cancer.
FDA Approves Revolution Medicines' Daraxonrasib for Metastatic Pancreatic Cancer
On August 26, 2026, the FDA approved Revolution Medicines' Rasonque (daraxonrasib, formerly RMC-6236) for adults with metastatic pancreatic adenocarcinoma who have received at least one prior line of systemic therapy. It is the first FDA-approved targeted therapy aimed at the active-state RAS(ON) protein family. The RAS(ON) molecular glue approval marks one of the biggest clinical advances in pancreatic cancer in nearly a decade.
FDA Approves Daraxonrasib as First Oral RAS-Targeted Drug for Pancreatic Cancer
The FDA approved Rasonque (daraxonrasib) on August 26, 2026 for metastatic pancreatic adenocarcinoma in patients previously treated with at least one systemic therapy. It is the first direct RAS-targeted oral drug approved in pancreatic cancer, a disease where more than 90% of patients carry KRAS mutations. The approval comes 44 years after RAS was identified as the first human oncogene in 1982.
FDA Clears Wave of Firsts
On this pageThe FDA approved a run of first-in-class therapies: Ultragenyx's Fayuvi (rebisufligene etisparvovec), a one-time AAV9 gene therapy delivering functional SGSH and the first treatment for Sanfilippo syndrome type A, with treated patients aged 2-5 maintaining or improving cognitive scores; Ionis's Zanvastro (zilganersen), first drug for Alexander disease, targeting GFAP buildup via quarterly intrathecal antisense dosing; Scholar Rock's Isembyld, first therapy targeting muscle loss in SMA for patients aged 2 and older on SMN2-directed treatment; and Eli Lilly's Onswik (insulin efsitora alfa), a once-weekly IgG2-Fc fusion basal insulin for adults with type 2 diabetes, approved September 24.
FDA Approves Ultragenyx Gene Therapy Fayuvi for Children with MPS IIIA
The FDA has approved Fayuvi (rebisufligene etisparvovec), a gene therapy developed by Ultragenyx Pharmaceutical, making it the first FDA-approved therapy for children with mucopolysaccharidosis type IIIA, also known as Sanfilippo syndrome type A. The rare inherited disease progressively damages the brain and nervous system, causing gradual loss of cognitive, speech and other developmental abilities.
FDA Approves FAYUVI, First Gene Therapy for Children with MPS IIIA
The FDA has approved FAYUVI, the first gene therapy for children with Sanfilippo syndrome type A (MPS IIIA), an ultra-rare, fatal lysosomal storage disease that mainly affects the central nervous system. FAYUVI is a one-time intravenous infusion that uses a modified, non-infectious AAV9 vector to deliver functional copies of the SGSH gene to patients' cells. The therapy had received orphan drug, fast track and breakthrough therapy designations from the FDA.
FDA Approves First Gene Therapy for Pediatric Patients with Sanfilippo Syndrome Type A
The FDA approved Fayuvi (rebisufligene etisparvovec-hopf), a one-time intravenous AAV9 gene therapy from Ultragenyx Pharmaceutical, as the first treatment for pediatric patients with mucopolysaccharidosis type IIIA, or Sanfilippo syndrome type A. In an open-label, single-arm multicenter study, treated patients aged 2 to 5 maintained or improved cognitive scores versus an untreated historical control. Patients receive corticosteroids from one day before infusion through at least eight weeks after, with warnings including thrombotic microangiopathy.
FDA Approves First Drug to Treat Alexander Disease
The FDA has approved Zanvastro (zilganersen) injection from Ionis Pharmaceuticals for Alexander disease in pediatric and adult patients, the first treatment for this rare neurological disorder and the first to target the abnormal GFAP protein buildup that drives it. Efficacy rested on a 49-patient randomized controlled study plus a 4-patient open-label substudy in infants under 2, with treated patients aged 5 and older showing better walking speed at 61 weeks. The antisense oligonucleotide is injected into the spinal canal every three months.
STAT+: Scholar Rock wins FDA approval for first drug to target SMA muscle loss
The FDA has approved Scholar Rock's Isembyld, the first therapy to target muscle loss in spinal muscular atrophy, for adults and children aged 2 and older already receiving SMA therapies that target SMN2. In a late-stage trial, Isembyld combined with an SMN2-targeting drug improved young patients' motor skills over a year while placebo recipients declined, a statistically significant difference. Approval was granted on Friday.
Scholar Rock scores long-awaited FDA approval, the first for muscle loss in SMA
FDA Approves Eli Lilly Once-Weekly Basal Insulin Onswik for Type 2 Diabetes
The FDA has approved Eli Lilly's once-weekly long-acting basal insulin Onswik (insulin efsitora alfa) for adults with type 2 diabetes, offering an alternative to daily insulin injections. The approval reflects a broader effort across insulin and GLP-1 drugs to extend dosing intervals for long-term treatment. Onswik now becomes a new treatment option for adult patients in the United States.
FDA approves Eli Lilly's weekly insulin Efsitora alfa for type 2 diabetes
The FDA has approved Eli Lilly's once-weekly basal insulin Efsitora alfa (brand name Onswik), announced on September 24, 2026, to improve glycaemic control in adults with type 2 diabetes alongside diet and exercise. Efsitora is a fusion protein linking a novel single-chain insulin variant to a human IgG2-Fc domain, extending half-life to allow weekly subcutaneous injection instead of daily dosing.
Cardiovascular Setbacks, Oncology and Obesity Wins
On this pageNovartis's pelacarsen lowered Lp(a) but missed its primary endpoint in Lp(a)HORIZON (8323 patients, 42 countries), sending Novartis shares down 5% and Ionis down 9%, and eplontersen showed no outcome benefit in ATTR-CM (rate ratio 0.89, P=0.28). Positive results dominated elsewhere: first-line trastuzumab deruxtecan reached median PFS of 14.3 versus 8.3 months for pembrolizumab plus chemo in HER2-mutant NSCLC (DESTINY-Lung04); 177Lu-PSMA-617 cut radiographic progression or death risk by 28% in PSMAddition; semaglutide was approved for MASH with F2/F3 fibrosis based on ESSENCE; and once-weekly survodutide produced 12.2-13.0% weight loss versus 5.4% placebo at week 76.
Novartis pelacarsen misses primary endpoint in Lp(a)HORIZON trial
Novartis reported on September 4 that the Lp(a)HORIZON trial of pelacarsen missed its primary endpoint. The trial enrolled 8323 patients across 42 countries and was the first outcome trial designed to test whether lowering Lp(a) reduces cardiovascular events; Lp(a) fell, but cardiovascular events were not significantly reduced, despite earlier studies showing pelacarsen can lower Lp(a) by up to about 80%. The result forces a revaluation of the entire Lp(a)-lowering field, showing that lowering the lipid does not itself translate into fewer events.
Pelacarsen Lowered Lp(a) but Failed to Cut Cardiovascular Risk in Pivotal Trial
Pelacarsen, Novartis's antisense drug targeting Lp(a), significantly lowered Lp(a) but failed to translate that into reduced cardiovascular risk in a pivotal trial, the first to test whether lowering Lp(a) cuts cardiovascular risk. Novartis shares fell 5% after the news and Ionis fell 9%. The result clouds the most closely watched lipid target after PCSK9, where several small nucleic acid drugs and small molecules are in late-stage trials.
Novartis Lp(a) drug fails to lower cardiovascular risk in closely watched ph. 3 trial
Novartis' Ionis-partnered Lp(a)-lowering drug failed to reduce patients' risk of heart attack, stroke, or other major cardiovascular events in its first late-stage trial. The result comes in the first phase 3 test of a drug aimed at Lp(a), a known cardiovascular risk factor, and undermines the strategy of targeting the molecule to cut cardiovascular risk. What changes is the outlook for Lp(a) reduction as a cardioprotective approach.
Eplontersen for Transthyretin Amyloid Cardiomyopathy.
Eplontersen, an antisense oligonucleotide that reduces hepatic transthyretin production, did not reduce cardiovascular death or recurrent cardiovascular events in transthyretin amyloid cardiomyopathy. In the phase 3 CARDIO-TTRansform trial, 1432 patients received subcutaneous eplontersen 45 mg or placebo every 4 weeks for 140 weeks; the primary composite occurred at a rate ratio of 0.89 (95% CI, 0.73 to 1.09; P = 0.28). The finding leaves no demonstrated outcome benefit for eplontersen on top of standard treatment in ATTR-CM.
Trastuzumab Deruxtecan Extends Median PFS to 14.3 Months as First-Line Therapy in HER2-Mutant Advanced NSCLC
In the phase III DESTINY-Lung04 trial, first-line trastuzumab deruxtecan (Enhertu) gave a median progression-free survival of 14.3 months in patients with HER2-mutant advanced non-small cell lung cancer, versus 8.3 months with pembrolizumab plus chemotherapy. It is the first HER2-targeted therapy to show superiority over standard treatment in this setting.
[177Lu]Lu-PSMA-617 in patients with PSMA-positive metastatic androgen pathway modulator-naive/sensitive prostate cancer (PSMAddition): a phase 3 randomised, controlled trial.
Adding 177Lu-PSMA-617 to androgen deprivation therapy plus an androgen receptor pathway inhibitor reduced the relative risk of radiographic progression or death by 28% in PSMA-positive metastatic APMN/S prostate cancer, meeting the primary endpoint of prolonged radiographic progression-free survival. In the phase 3 PSMAddition trial, 572 patients per arm were randomised; radiographic progression or death occurred in 24% of the 177Lu-PSMA-617 arm versus 30% of the control arm. Grade 3 or worse adverse events occurred in 51% versus 43%, with dry mouth the most common event in the 177Lu-PSMA-617 arm.
Novo Nordisk's Semaglutide Approved for MASH with Moderate to Severe Liver Fibrosis
Novo Nordisk's semaglutide injection (Wegovy/Novo Nordisk's brand Nuvo Ying) has been approved for MASH in patients with moderate to severe liver fibrosis. The approval is based on the primary results of part 1 of the ESSENCE outcomes trial, which enrolled 1,197 MASH patients with biopsy-confirmed F2 or F3 fibrosis. Semaglutide met both liver histology primary endpoints versus placebo.
Survodutide Once Weekly for the Treatment of Adults with Obesity.
Once-weekly survodutide, a glucagon receptor-GLP-1 receptor dual agonist, produced mean body-weight reductions of 12.2% at 3.6 mg and 13.0% at 6.0 mg at week 76, versus 5.4% with placebo, in 725 adults with obesity but no diabetes. Weight loss of at least 5% occurred in 72.6% and 71.9% of the survodutide groups versus 46.3% on placebo (P<0.001). Gastrointestinal symptoms were the most common adverse events, and no deaths were reported.
Xenotransplantation, Editing and Policy Advances
On this pageAir Force Medical University maintained a gene-edited pig liver for 11 days in a brain-dead recipient, the first orthotopic pig-to-human liver xenotransplant, while a gene-edited porcine kidney (EGEN-2784) sustained dialysis independence for 271 days and bridged a patient to a successful human allotransplant. Correctsequence's base editing therapy CS-101/CS-206 cured beta-hemoglobinopathy patients across ethnic backgrounds, and Nature published KIT epitope editing enabling non-genotoxic conditioning. Intellia's in vivo CRISPR therapy lonvo-z won FDA priority review for hereditary angioedema with a March 10, 2027 PDUFA date. Separately, a pervasive RT-qPCR artifact was shown to inflate reported RNA-targeting CRISPR knockdown, and China's NHSA launched a pilot pre-approval pricing pathway for high-level new medical technologies.
Gene-Edited Pig Liver Transplanted Into Brain-Dead Human Maintains Function for 11 Days
A team at Air Force Medical University led by Dou Kefeng transplanted a gene-edited pig liver orthotopically into a brain-dead human recipient and maintained liver function for 11 days. The result extends earlier auxiliary metabolic support from engineered pig livers to full orthotopic pig-to-human liver xenotransplantation, which has remained challenging because of the liver's immunological and physiological complexity.
Porcine kidney xenotransplantation as a bridge to allotransplantation: a first-in-human study.
A gene-edited porcine kidney (EGEN-2784) transplanted into a patient with end-stage kidney disease functioned immediately and maintained dialysis independence for 271 days before failing after immunosuppression reduction, with thrombotic microangiopathy despite negative donor-specific crossmatch. No porcine pathogen transmission or anti-HLA antibody change occurred. 82 days after nephrectomy, the patient received a human kidney allotransplant with immediate function and no sensitisation during 231 days of follow-up.
Base Editing Therapy CS-101/CS-206 Cures Beta-Hemoglobinopathy Patients Across Genetic Backgrounds
A base editing therapy developed with the transformer Base Editor (tBE), CS-101/CS-206 from Correctsequence Therapeutics, achieved clinical cure across patients with different genetic backgrounds, according to results published in Cell Stem Cell on September 7, 2026. Following 100% cure in Chinese beta-thalassemia patients, the study shows tBE is safe and effective in sickle cell disease and in Southeast and South Asian beta-thalassemia patients, supporting broad applicability across ethnicities.
Non-genotoxic transplantation and in vivo selection through epitope editing.
Epitope editing of KIT lets transplanted haematopoietic stem/progenitor cells escape anti-KIT monoclonal antibodies, enabling non-genotoxic in vivo conditioning and selection. Adenine base editing or prime editing introduced the KIT mutations together with BCL11A erythroid enhancer disruption to induce fetal haemoglobin for sickle cell disease and β-thalassaemia. Edited haematopoietic cells progressively enriched under anti-KIT selective pressure without clonal selection, allowing chemotherapy- and radiotherapy-free haematopoietic replacement.
FDA Grants Priority Review to Intellia's In Vivo CRISPR Therapy lonvo-z for HAE
The FDA has accepted Intellia Therapeutics' BLA for lonvoguran ziclumeran (lonvo-z), an in vivo CRISPR therapy for hereditary angioedema, with priority review and a PDUFA goal date of March 10, 2027. The agency does not plan to convene an advisory committee. If approved, lonvo-z would be the first approved in vivo CRISPR therapy and the only single-treatment option for HAE.
A pervasive RT–qPCR artifact inflates RNA knockdown by RNA-targeting CRISPR
RT-qPCR amplicons spanning the guide RNA binding site falsely report RNA knockdown by RNA-targeting CRISPR systems. For RNase-dead Csm targeting XIST, a spanning amplicon showed 90% apparent knockdown while a downstream amplicon showed 14%, and WT Csm knockdown was inflated (90% spanning versus 35% downstream). The artifact, driven by copurifying gRNAs inhibiting RT-qPCR, affects Csm, Psp Cas13b and CasRx, meaning published knockdown efficiencies measured this way may be overestimated.
China's NHSA to Trial Pre-Approval Pricing Mechanism for High-Level New Medical Technologies
On September 15, China's National Healthcare Security Administration published a notice (document Yibao Fa [2026] No. 23) establishing a trial pre-approval system for medical service pricing of high-level new technologies and products. The mechanism moves the pricing acceptance stage earlier so that regulatory approval for clinical use links directly to charging authorization, and it pairs this with constraints on consumable prices, conditional charging and value assessment to filter routine iterative products and guard against misuse. Companies will be pushed to prepare clinical and economic evidence in parallel from early development stages.
China's NHSA Pilots Pre-Approval Pricing Pathway for New Medical Technologies and Products
China's National Healthcare Security Administration issued a notice on September 15 establishing a pilot pre-approval pricing system for high-level new technologies and products, allowing hospitals to apply for pricing pre-approval from the start of clinical research rather than after regulatory approval. Under the system, a tertiary hospital applies directly to provincial medical insurance departments, and once the first hospital files, others need not repeat the process. Approved technologies can then convert pre-approval into formal pricing through new, conditionally added, or compatible price items, with real-world value assessment embedded throughout.