Biomedicine Daily · Sunday, 6 September 2026
CBA FRONTIER INSIGHTS
Novartis Pelacarsen Cuts Lp(a) but Misses on Cardiovascular Events in Phase 3
Novartis and Ionis reported that pelacarsen, an antisense oligonucleotide targeting Lp(a), failed to reduce the risk of cardiovascular death, heart attack, stroke, or other major cardiovascular events versus placebo in the Phase 3 Lp(a)HORIZON trial, despite earlier trials showing it drastically lowers the lipid-and-protein particle. It was the first late-stage test of whether lowering Lp(a), a known cardiovascular risk factor, translates into protection. Novartis shares fell 5% and Ionis fell 9% on the news. The result clouds the most closely watched lipid target after PCSK9, where Amgen and Eli Lilly also have therapies in development, and undermines Lp(a) reduction as a cardioprotective strategy.
Clinical readouts and safety
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.
Novartis pelacarsen fails to improve cardiovascular events in Lp(a)HORIZON phase III trial
Novartis reported topline results from the Lp(a)HORIZON phase III trial of pelacarsen, an Lp(a)-targeting oligonucleotide therapy, in patients with elevated Lp(a) and established cardiovascular disease. Pelacarsen did not improve cardiovascular events compared with placebo. The result adds new evidence on the relationship between Lp(a) lowering and cardiovascular outcomes.
STAT+: Novartis’ experimental cardiovascular drug fails a pivotal study
Novartis' pelacarsen failed to reduce the risk of cardiovascular death or emergencies such as heart attack or stroke compared with placebo in the Phase 3 HORIZON trial, despite earlier trials showing it drastically lowered Lp(a), a lipid-and-protein particle linked to severe heart problems. The outcome is a setback for Novartis and for the broader effort to target Lp(a), where Amgen and Eli Lilly are also developing therapies.
Phase 3 Trial of Oral Infigratinib in Children with Achondroplasia.
Once-daily oral infigratinib (0.25 mg per kilogram) for 52 weeks increased annualized height velocity in children with achondroplasia by 1.74 cm per year versus placebo (P<0.001), with a height z score gain of 0.32 and no change in the upper-to-lower body segment ratio. In the 114-patient phase 3 trial, adverse events occurred in 96% of infigratinib recipients and 95% of placebo recipients, with no investigator-attributed drug-related serious events. It offers an oral treatment option targeting the FGFR3 pathway underlying achondroplasia.
Industry and deals
GSK licenses preclinical HMPL-A830 from Hutchison China MediTech in deal worth up to $1.295 billion
GSK has licensed global rights outside Greater China to HMPL-A830, a Hutchison China MediTech candidate that has not yet entered human trials, in a deal worth up to $1.295 billion with an upfront payment of $110 million. The agreement was signed on September 3, 2026. The asset belongs to Hutchison's ATTC class, which builds on its antibody-drug conjugate work.
Research papers
Structural basis for host membrane binding and remodeling by invading malaria parasites.
The endogenous structure of the Plasmodium falciparum moving junction, purified from invasion-stalled parasites, reveals a sailboat-shaped 1:1:1:1 complex of PfAMA1, PfRON2, PfRON4 and PfRON5. Two PfRON2 transmembrane helices anchor the complex in the red blood cell membrane, while PfRON2/4/5 form a basic platform that wedges seven amphipathic helices into the bilayer, indicating active host-membrane remodeling. Guided by the structure, a rationally designed small protein binder inhibits invasion.
Reconstituting human primitive streak formation through extra-embryonic cell coordination.
A defined co-culture system pairing human embryonic stem cells with extra-embryonic cell types mimicking amniotic ectoderm, trophoblast, and extra-embryonic mesoderm shows that extra-embryonic cells alone can recapitulate human primitive streak formation. Microengineering the spatial and molecular interactions among these cells also revealed extended developmental potential. The system opens previously inaccessible stages of human early gastrulation to experimental manipulation.
Metabolic regulation of calcium homeostasis via SERCA succination.
Fumarate covalently modifies SERCA2b at Cys875, inhibiting ER calcium uptake and disrupting calcium homeostasis. A Cys875Ser mutant resists fumarate-induced inhibition, and Drosophila knock-in flies carrying the corresponding mutation preserve ER calcium homeostasis and are protected from hyperglycemia, glucose intolerance, and reduced survival on a high-sugar diet. Pharmacological fumarate reduction or allosteric SERCA activation phenocopies these protective effects.
A Zoonotic Orthonairovirus from Febrile Patients in China.
Pervasive noise in human pre-mRNA splice site selection.
Deep sequencing across RNA compartments in human cells reveals abundant cryptic splicing and pervasive usage of low-fidelity splice sites, likely arising from stochastic spliceosome recruitment or binding. These non-productive transcripts are rapidly degraded through nuclear and cytoplasmic surveillance pathways. The work quantifies widespread stochastic splicing noise, challenging the view that splicing is highly efficient and accurate.
Complete biosynthesis of the anticancer cephalotaxinone and homoerythratine.
The complete biosynthetic pathways of cephalotaxinone and homoerythratine, alkaloids from endangered Cephalotaxus species related to the leukemia drug homoharringtonine, have been identified using multi-omics analysis and synthetic standards. Two highly homologous P450 enzymes, CfCYP2 and CfCYP3, catalyze a rare divergent oxidation yielding two structurally distinct alkaloids, and key residues controlling this divergence were pinpointed. Both pathways were reconstituted in N. benthamiana, opening a route to production independent of limited natural resources.
A deceptive fungating breast mass: giant fibroadenoma with multiple epidermal inclusion cysts mimicking malignancy
A 22-year-old woman's approximately 10 cm fungating, ulcerated breast mass, complicated by methicillin-resistant Staphylococcus aureus infection, was confirmed after enucleation to be a giant fibroadenoma with multiple epidermal inclusion cysts, not malignancy. Multiple core biopsies had shown fibroadenoma despite rapid progression. The breast-preserving surgery spared the nipple-areolar complex, and at six months there was no clinical or ultrasonographic recurrence.
Identifying heat-related diagnoses in emergency department visits among adults in Chicago: A heat-wide association study.
A heat-wide association study of 916,904 acute-care visits among 372,140 adults across four Chicago health systems (2011 to 2023) identifies diagnoses linked to extreme heat beyond the usual restricted categories. After quasi-Poisson screening and case-crossover modeling, 33 clinically reportable diagnoses showed elevated cumulative odds over lags 0 to 3, including fluid-balance and renal disorders, dermatologic conditions, multiple sclerosis, and injuries. The full-diagnostic-spectrum approach broadens the clinical picture of heat-associated morbidity.
Methods and resources
Efficient Calculation of Absorption Spectra of Platinum Complexes Used as Luminescent Probes for Cancer Detection
Benchmarking of methods for computing UV-Vis absorption spectra of a Pt(II) pincer complex, alone and intercalated in a small DNA model, shows that the Tamm-Dancoff approximation and resolution-of-identity approximations speed up TD-DFT considerably at only a modest accuracy cost. PBEh-3c geometry optimization matches conventional DFT efficiency gains with errors comparable to TDA, while GFN-xTB is faster but less accurate; the exchange-correlation functional, with PBE0 performing well, is the largest uncertainty. The work supplies a computational protocol for screening luminescent transition metal probes that target DNA abnormalities.