Triglyceride drugs: they prevent pancreatitis, but heart benefit is still unproven
On 16 October 2026 the EU medicines committee backed Sobi’s Tryngolza (olezarsen) for adults with severe hypertriglyceridaemia (sHTG), very high blood fats. Six weeks earlier, Novartis’s pelacarsen failed to prevent heart attacks despite lowering Lp(a), another blood fat. Read together, a decade of trials shows a split: drugs that lower triglycerides prevent pancreatitis, but they have rarely prevented heart attacks or strokes.
| Drug · trial | Primary endpoint | Result | Fewer pancreatitis? |
|---|---|---|---|
| Olezarsen (Tryngolza) · CORE / CORE2 sHTG | % change in TG at 6 months | –49% to –72% vs placebo; P<0.001 | Yes: –85% (rate ratio 0.15); 1 attack avoided per 20 treated, per 4 after a past attack |
| Olezarsen · Balance FCS | % change in TG at 6 months | Significant, P=0.0009 | Yes: 0 vs 11 attacks |
| Plozasiran (Redemplo) · PALISADE FCS | Median % change in TG at 10 months | –80% vs –17% placebo | Yes: odds ratio 0.17, P=0.03 |
| Plozasiran · SHASTA-3 / SHASTA-4 sHTG | % change in TG at 12 months | –79% / –81% vs placebo | Yes: –78% (pooled) |
| Volanesorsen (Waylivra) · APPROACH FCS | % change in TG at 3 months | –77% vs +18% placebo | Yes: 1 vs 6* (P=0.019) |
| Pradigastat (Novartis) · Phase 3 FCS | % change in TG at 12 weeks | Not published; not filed | Not an endpoint |
| Glybera (uniQure) · single-arm studies LPL deficiency | Fat clearance after meals | EU approval 2012 (exceptional circumstances) | No randomised data |
▲ pancreatitis attacks reduced; ▼ development failed. TG = triglycerides. FCS = familial chylomicronaemia syndrome, the rare inherited form; sHTG = severe hypertriglyceridaemia from any cause (US label TG ≥500 mg/dL; EU opinion ≥880 mg/dL, 10 mmol/L). *Pooled APPROACH and COMPASS.
| Drug · trial | Patients | Primary endpoint | Fewer events? |
|---|---|---|---|
| Icosapent ethyl (Vascepa, Amarin) · REDUCE-IT | High TG, statins, n=8,179 | 5-part heart events | Yes: HR 0.75 (17.2% vs 22.0%)** |
| Omega-3 acids (Epanova, AstraZeneca) · STRENGTH | High TG, low HDL, n=13,078 | 5-part heart events | No: 12.0% vs 12.2%; stopped 2020 |
| Pemafibrate (Kowa) · PROMINENT | Diabetes, high TG, n=10,497 | Heart events | No: HR 1.03 (TG –26%) |
| Fenofibrate · FIELD | Diabetes, n=9,795 | Coronary events | No: HR 0.89, not significant |
| Pelacarsen (Novartis) · Lp(a)HORIZON | High Lp(a), heart disease, n=8,323 | 4-part heart events | No: missed (Sep 2026) |
| Inclisiran (Leqvio, Novartis) · ORION-4 | Heart or vessel disease, n=16,124 | 4-part heart events | Pending: due Oct 2026; VICTORION-2P May 2027 |
**Debated: the mineral-oil placebo may have raised risk in the control group. Leqvio lowers LDL cholesterol, the one blood fat where lowering is proven to cut heart events; it was approved on its LDL effect.
| Product | Approved for | Reported sales | Company ambition | Market peak estimate |
|---|---|---|---|---|
| Tryngolza US (Ionis) | FCS 12/24; sHTG 6/26 (US) | FY 25: USD 105M; H1 26: USD 32M (Q2 26: USD 5M, after price cut); FY 26 guide: USD 100–110M | Peak above USD 3B | About USD 3B |
| Tryngolza ex-US (Sobi) | FCS 9/25; sHTG opinion 10/26 (EU) | SEK 47M in Q2 26 | Peak above SEK 10B | Not published |
| Redemplo (Arrowhead) | FCS: US 11/25, EU 6/26 | Not reported separately | Not given | Not published |
| Waylivra (Ionis; Sobi in Europe) | FCS: EU 5/19 (conditional) | Not reported separately | — | — |
US list prices: Tryngolza USD 40,000 a year since April 2026 (from USD 595,000); Redemplo USD 60,000 a year. Sobi counts about 1 million sHTG patients in Europe with TG above 880 mg/dL, about 300,000 of them not controlled by current treatment; Ionis targets about 3 million US patients, 1 million at high risk.
In plain words
What happened. New injections can cut triglycerides, a type of blood fat, by more than half. In people with very high levels, they also prevent attacks of pancreatitis, a painful and sometimes deadly inflammation of the pancreas. The EU is about to approve one of them, Sobi’s Tryngolza, for a much larger group of patients.
Why it matters. Lowering blood fats other than LDL cholesterol has rarely prevented heart attacks. Novartis’s recent failure with a drug against Lp(a), another blood fat, added to that record. So these drugs are worth what they prevent in pancreatitis, a rarer event than heart attacks, and health systems will judge their price on that.
The key question Can the price hold when the value rests on pancreatitis alone? Neither olezarsen nor plozasiran has reported a heart-outcome trial, and STRENGTH, PROMINENT, FIELD and now Lp(a)HORIZON give little reason to expect a heart benefit. In CORE/CORE2, 20 patients had to be treated for a year to avoid one attack, 4 among those who had already had one: at the US list price of USD 40,000 a year, about est. USD 0.8M and est. USD 0.16M per attack avoided, before rebates and hospital savings. Ionis chose volume over price: it cut the list price by 93% in April 2026 and only then raised its peak-sales guidance to above USD 3B (from above USD 2B in January), which at list price means about est. 75,000 patients, some 7.5% of the 1 million high-risk US patients it targets. Outside the US the FCS price is still at rare-disease level: Outside the US the FCS price is still at rare-disease level: in Germany, Sobi’s monthly 80 mg pen is listed at EUR 29,800, about calc. EUR 358,000 a year against USD 40,000 in the US; in Canada, where Ionis keeps the rights, the submitted price of CAD 492,000 a year was judged cost-effective only with a cut of 75% or more (CAD 3.0M per QALY gained in the base case). As most European countries set one price per medicine across its uses, the sHTG launch in 2027 will likely force a similar reset in Europe. Sobi’s Q3 26 report on 27 October is the first chance to hear how it plans to price the wider label.
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