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FCS Weekly — Issue 1 · November 13, 2026

Qingyang · FCS Foundation Board Member & Tech Chair, FCS Foundation

This week's top stories

1. Plozasiran cuts pancreatitis risk by 78% in severe hypertriglyceridemia — full SHASTA-3/4 results published in the New England Journal of Medicine.
2. Three years on: the PALISADE extension shows plozasiran's triglyceride lowering holds up in FCS.
3. A first for gene editing: one infusion of CTX310 cut triglycerides 63% in a small early trial — while Ionis halves its 2026 Tryngolza sales outlook.

Research & new treatments

Plozasiran for severe hypertriglyceridemia: pancreatitis risk down 78% (NEJM, Nov 5)

Two identical Phase 3 trials (SHASTA-3 and SHASTA-4) enrolled 757 adults with severe hypertriglyceridemia, randomized 2:1 to plozasiran 25 mg or placebo every three months. At 12 months, median triglycerides were down 79% and 81% from baseline in the two trials; 91% and 93% of patients on plozasiran reached triglycerides below 500 mg/dL, versus about half on placebo. Adjudicated acute pancreatitis occurred at 1 vs 5 events per 100 patient-years (rate ratio 0.22, P = 0.008) — a 78% lower rate. Adverse events occurred in 73% of patients in both arms. The trials were funded by Arrowhead Pharmaceuticals. Note this was in severe hypertriglyceridemia broadly, not FCS specifically.

Three-year PALISADE data in FCS (AHA Scientific Sessions, Nov 7–9)

In the PALISADE long-term extension, 65 of the original 75 participants continued treatment; median baseline triglycerides were 2,259 mg/dL. Through 24 months of the extension — up to 36 months of total treatment — median triglycerides stayed 76% below baseline and APOC3 89% below; 57% of patients were below 880 mg/dL and 48% below 500 mg/dL at month 24. Three adjudicated pancreatitis events were reported. The extension had no placebo group, so these results are descriptive. Presented by Dr. Robert Rosenson; Arrowhead press release, Nov 7.

One-shot gene editing for severe high triglycerides: CTX310 (AHA, Nov 9)

CRISPR Therapeutics' CTX310 — a one-time, in vivo CRISPR/Cas9 therapy that edits the ANGPTL3 gene in the liver — reported first Phase 1b data in 10 patients with severe hypertriglyceridemia (median baseline triglycerides above 1,000 mg/dL). A single infusion cut ANGPTL3 by a mean 65% and triglycerides by 63% at day 30, with reductions maintained at 90 days in the seven patients followed that long. There were no treatment-related serious adverse events and no clinically relevant liver enzyme elevations. The FDA has granted CTX310 Regenerative Medicine Advanced Therapy (RMAT) designations for severe hypertriglyceridemia and elevated LDL cholesterol. Caveats: tiny, open-label, short follow-up, company-reported and not yet peer-reviewed — early promise, not proof.

Blood purification for triglyceride-induced pancreatitis: what helps, and when (Nov 8)

A single-center retrospective study of 204 patients with hypertriglyceridemia-induced acute pancreatitis compared hemoperfusion plus continuous venovenous hemofiltration (HP + CVVH) with CVVH alone. Overall, adding hemoperfusion did not reduce severe pancreatitis — but in patients whose CRP (an inflammation marker) was roughly 195–297 mg/L, it did. Secondary measures (inflammation levels, ICU stay, time to feeding) looked better with the combination, at higher blood-purification costs. Takeaway: any benefit depends on how inflamed the patient is — a decision for the ICU team, not a routine add-on.

Recently published — not this week's news

• A rare cause of FCS in a 5-month-old baby (JCEM Case Reports, published Oct 5, 2026): FCS caused by a homozygous variant in the LMF1 gene — an exceedingly rare cause, and presentation in infancy is rarer still. Early diagnosis and a low-fat diet brought triglycerides down and prevented pancreatitis. A reminder that FCS can appear in infancy, and that genetic testing can find the cause.
• Plasma exchange in severe hypertriglyceridemia emergencies (Molecular Genetics and Metabolism Reports, Sept 2026): a 21-patient retrospective case series from a multinational group found therapeutic plasma exchange and/or exchange transfusion rapidly lowered lipids and eased symptoms in emergency admissions, including recurrent pancreatitis cases. Retrospective and uncontrolled — evidence of use, not of superiority over standard care.

Regulation & access

• England and Wales: NICE backs both olezarsen and plozasiran for FCS (Oct 28, via Action FCS): NICE accepted both medicines for use in England and Wales under its cost-comparison process — the first time people with FCS there have a choice of primary treatment alongside diet. Action FCS and Metabolic Support UK contributed patient evidence to the appraisal.
• Europe: CHMP positive opinion for Tryngolza in severe hypertriglyceridemia (Oct 16; noted in Ionis's Q3 results, Nov 9): EMA's committee recommended extending Tryngolza (olezarsen) to adults with severe hypertriglyceridemia (fasting triglycerides ≥880 mg/dL); a final European Commission decision is expected in Q4 2026. If confirmed, it would be the first RNA-targeted therapy authorized in the EU for severe hypertriglyceridemia at that level.

Industry

• Ionis Q3: Tryngolza sales ramp slower than expected (company press release, Nov 9): TRYNGOLZA U.S. net sales were $9M in Q3 ($41M over nine months); Ionis cut its 2026 Tryngolza sales guidance to about $50M, from $100–110M, citing a more gradual launch ramp. Total revenue guidance ($875–900M) was reaffirmed. For patients, the practical read: the drug is available, but uptake is slow — access and awareness remain the bottleneck, not approval.

Community

• FCS Awareness Day, November 6: The Foundation for Triglyceride Disorders marked FCS Awareness Day with patient and caregiver voices, and Action FCS ran its 10g Fat Challenge — a day on no more than 10g of fat — with 10 days of low-fat recipes to mark its 10th anniversary.

Join us

Living with FCS or caring for someone who is? Join the FCS Support Group on Facebook: facebook.com/groups/livingwithfcs — patients, families and caregivers sharing practical experience.

Sources

1. Watts GF et al. Plozasiran for Severe Hypertriglyceridemia and Risk of Pancreatitis. N Engl J Med. 2026;395(18):1805–1817. https://pubmed.ncbi.nlm.nih.gov/42981569/
2. Arrowhead Pharmaceuticals. Arrowhead Pharmaceuticals Presents Plozasiran Data Highlighting Sustained Triglyceride Reductions and Reduced Acute Pancreatitis Rates (press release, Nov 7, 2026). https://www.businesswire.com/news/home/20261107972891/en/Arrowhead-Pharmaceuticals-Presents-Plozasiran-Data-Highlighting-Sustained-Triglyceride-Reductions-and-Reduced-Acute-Pancreatitis-Rates
3. HCPLive. PALISADE Extension Supports Plozasiran's Efficacy, Safety in Familial Chylomicronemia (Nov 9, 2026). https://www.hcplive.com/view/palisade-extension-supports-plozasiran-s-efficacy-safety-in-familial-chylomicronemia
4. CRISPR Therapeutics. CRISPR Therapeutics Presents Phase 1b Data for CTX310 Demonstrating Reductions in ANGPTL3 and Triglycerides in Patients with Severe Hypertriglyceridemia at the American Heart Association Scientific Sessions 2026 (press release, Nov 9, 2026). https://investingnews.com/crispr-therapeutics-presents-phase-1b-data-for-ctx310-r-demonstrating-reductions-in-angptl3-and-triglycerides-in-patients-with-severe-hypertriglyceridemia-at-the-american-heart-association-scientific-/
5. Ionis Pharmaceuticals. Ionis reports third quarter 2026 financial results and highlights progress on key programs (press release, Nov 9, 2026). https://www.stockwatch.com/News/Item/U-b20261109740265-U!IONS-20261109/U/IONS
6. Li A et al. Efficacy Heterogeneity of Hemoperfusion Plus Continuous Venovenous Hemofiltration for Hypertriglyceridemia-Induced Acute Pancreatitis Stratified by Severity of Inflammatory Response. Ther Apher Dial. 2026 Nov 8 (online ahead of print). https://pubmed.ncbi.nlm.nih.gov/43000034/
7. Kumar PR et al. A rare case of familial chylomicronemia in infancy due to homozygous LMF1 variant. JCEM Case Rep. 2026;4(11):luag164. https://pubmed.ncbi.nlm.nih.gov/42831121/
8. Stefanutti C et al. Efficacy of plasma exchange and exchange transfusion in the clinical management of severe hypertriglyceridemia in emergency. Mol Genet Metab Rep. 2026;12:101353. https://pubmed.ncbi.nlm.nih.gov/42756739/
9. Action FCS. NICE publishes guidelines for new therapies (Oct 28, 2026). https://www.actionfcs.org/news/nice-publishes-guidelines-for-new-therapies/
10. Sobi. Sobi receives positive CHMP opinion for TRYNGOLZA (olezarsen) for the treatment of severe hypertriglyceridemia (sHTG) (Oct 16, 2026). https://mb.cision.com/Main/14266/4409832/4321959.pdf
11. The Foundation for Triglyceride Disorders. The Foundation for Triglyceride Disorders Marks FCS Awareness Day, Nov. 6, With the Voices of Patients and Caregivers (press release, Nov 5, 2026). https://www.morningstar.com/news/pr-newswire/20261105la90497/the-foundation-for-triglyceride-disorders-marks-fcs-awareness-day-nov-6-with-the-voices-of-patients-and-caregivers
12. Action FCS. FCS Awareness Day 2026. https://www.actionfcs.org/get-involved/events/fcs-awareness-day-2026/

Company press releases are marked as such; their figures have not been peer-reviewed. This digest summarizes published research and company announcements for information only. It is not medical advice — talk to your doctor before making any change to your treatment or diet.