SHTG Daily Digest — Weiss Lab

It's a quiet cycle on both fronts — no top-tier-journal lipid papers cleared the bar, but the biggest industry story is a jolt: Novartis and Ionis's Lp(a)-lowering drug pelacarsen just failed its pivotal cardiovascular outcomes trial, raising hard questions for the whole class of RNA-targeting lipid therapies (including the APOC3/ANGPTL3 programs this show tracks).

A quiet cycle on both fronts — no top-tier lipid papers cleared the bar in PubMed this week, and no genuinely new SHTG/Arrowhead/Alnylam/Ionis industry stories broke in the last 5 days beyond what's already been covered (Tryngolza's sHTG approval and Arrowhead's ESC '26 plozasiran data remain the dominant recent storylines).

This is a quiet, largely repeat cycle — the CTX310 (ANGPTL3 base-editing) durability letter and the Arrowhead-vs-Ionis ESC Congress safety showdown that drove the last digest remain the dominant SHTG stories, with nothing genuinely new clearing the bar on either the science or industry side since two days ago.

ESC Congress in Munich delivered the payoff this cycle predicted last time — CRISPR Therapeutics published one-year durability data for its ANGPTL3 base-editing candidate CTX310 in NEJM, while Arrowhead used the same meeting to lay out a case that plozasiran (Redemplo) is at least as good as, and possibly safer than, Ionis's Tryngolza in severe hypertriglyceridemia.

No new top-tier lipid papers broke this cycle, but a strong human ANGPTL3-deficiency kinetics study and a novel TREM2–APOC3 mechanism paper stood out on the science side, while the industry side was quiet on new sHTG-specific news in the last five days — the main thing to watch is ESC Congress in Munich, though this year it's Alnylam's amyloid-cardiomyopathy franchise, not its lipid pipeline, in the spotlight.

No top-tier-journal SHTG papers landed this cycle, but a broadened PubMed pull surfaced two drug-focused reviews on plozasiran and olezarsen plus a Korean GWAS turning up a novel ANGPTL3 variant, while the industry side stayed quiet with nothing new in the 5-day window from Ionis, Arrowhead, or Alnylam.

No top-tier journal papers on SHTG/ANGPTL/APOC3/LPL cleared the bar this cycle (next-best-tier picks below on ANGPTL3 inhibition and APOC3-targeted siRNA are still worth a read), and it's a quiet week for Arrowhead/Alnylam/Ionis press coverage ahead of the SHASTA-3/4 late-breaker at ESC on August 30.

No top-tier trial readouts this cycle, but the science side keeps chipping at the APOC3/ANGPTL3/ANGPTL4/LPL mechanism (postprandial handling, CKD dyslipidemia, pancreatitis risk prediction) while the industry side remains anchored by Arrowhead's positive plozasiran Phase 3 data, with the full readout due at ESC on August 30.

A quiet cycle on both fronts — the only qualifying PubMed hit is a JAMA news synopsis recapping June's Tryngolza approval rather than new primary research, and no fresh trade-press stories on SHTG, Arrowhead, Alnylam, or Ionis cleared the 5-day/dedup bar, with the field's most consequential items (Arrowhead's SHASTA-3/4 topline and Alnylam's Amvuttra-driven selloff) already covered in a recent episode.

No new top-tier journal papers this cycle — the science side is quiet reviews and case reports on the APOC3/LPL axis — while on the industry side Arrowhead bought itself a priority review voucher to speed its plozasiran (Redemplo) filing in severe hypertriglyceridemia, sharpening its race against Ionis's newly-expanded Tryngolza.