Ionis Pharmaceuticals (NASDAQ: IONS) CEO Brett Monia participated in a fireside chat Thursday September 10, 2026 at the Wells Fargo 21st Annual Healthcare Conference in Boston, disclosing TRYNGALZA (olezarsen, an antisense oligonucleotide that reduces apolipoprotein C-III production and lowers triglycerides) H1 2026 U.S. net product sales of $32 million (Q2 alone was $5 million) with full-year 2026 guidance of $100-110 million. The severe hypertriglyceridemia (sHTG) launch followed June 2026 FDA approval and represents the first indication expansion from the initial familial chylomicronemia syndrome (FCS) indication. Ionis raised peak sales guidance in the sHTG indication from $1 billion-plus to $2 billion-plus. The sHTG marketing application is under review in the European Union with potential launch in 2027. Ionis is also commercializing the September 3, 2026 FDA-approved ZANVASTRO (zilganersen, an antisense oligonucleotide) for Alexander disease, a first-in-class disease-modifying therapy for a rare progressive neurodegenerative disorder with no other approved therapies. The company acknowledged parallel setbacks in cardiovascular studies including the Novartis pelacarsen Phase 3 Lp(a)HORIZON miss reported September 4.
Ionis Pharmaceuticals (NASDAQ: IONS) and Royalty Pharma (NASDAQ: RPRX) both issued statements Friday September 4, 2026 following the Novartis pelacarsen Lp(a)HORIZON Phase 3 primary endpoint miss. Ionis, the original developer that licensed pelacarsen to Novartis in 2019, is entitled to potential low-double-digit tiered royalties on future net sales that now appear unlikely absent a resubmission based on a different endpoint or population. Royalty Pharma acquired a portion of Ionis's royalty rights on pelacarsen in a 2019 transaction and had modeled multi-hundred-million-dollar revenue on approval. Both companies emphasized the substantial Lp(a) reduction achieved in the trial and the value of the dataset for the broader Lp(a) research field. The miss lands within days of Ionis's September 3 FDA approval of Zanvastro (zilganersen) for Alexander disease, which provided commercial and pipeline offset. Analyst commentary noted that the Ionis antisense franchise remains strong despite the pelacarsen setback, with Wainua (eplontersen), Zanvastro, and the deep pipeline anchoring the platform.
Ionis Pharmaceuticals (NASDAQ: IONS) announced Thursday September 3, 2026 FDA approval of Zanvastro (zilganersen, an intrathecally-administered antisense oligonucleotide designed to reduce glial fibrillary acidic protein / GFAP production) for the treatment of Alexander disease in pediatric and adult patients. The approval is the first-ever disease-modifying therapy for Alexander disease, an ultra-rare autosomal dominant neurodegenerative disorder caused by GFAP gene mutations that presents in infancy through adulthood with progressive motor and cognitive decline. Approval landed 19 days ahead of the September 22, 2026 PDUFA target action date. In the registrational trial, walking speed stayed stable in Zanvastro-treated patients while control patients saw a 33% decline. FDA granted Ionis a Rare Pediatric Disease Priority Review Voucher (PRV) alongside the approval; PRVs have historically sold for $150-350 million on secondary markets. Zanvastro follows Ionis's Wainua (eplontersen) commercial franchise for hereditary transthyretin amyloid polyneuropathy and lands after the August 28 CARDIO-TTRansform ATTR-CM Phase 3 primary endpoint miss for the same molecule.
The Rare Pediatric Disease Priority Review Voucher (PRV) granted to Ionis Pharmaceuticals (NASDAQ: IONS) alongside the Zanvastro (zilganersen) FDA approval Thursday September 3, 2026 for Alexander disease adds substantial commercial value to the launch economics. PRVs have historically sold for $150 to $350 million on the secondary market and can be transferred an unlimited number of times. Recent PRV transactions: Arrowhead Pharmaceuticals sold a PRV for $215 million cash in connection with the plozasiran FCS approval earlier in 2026; other recent PRV sales have priced in the $100-200 million range. Ionis has not yet disclosed plans for the PRV — the company can use it to accelerate FDA review of a future NDA/BLA submission (from standard 10-12 months to priority 6 months) or sell it to another drug developer. The PRV program has faced periodic legislative sunset threats and is currently authorized through December 2026; the incentive continues to drive investment into rare pediatric disease programs where the commercial market alone would not economically justify development.
Ionis Pharmaceuticals (NASDAQ: IONS) awaits its September 22, 2026 PDUFA target action date for zilganersen (an intrathecally-administered antisense oligonucleotide designed to reduce production of glial fibrillary acidic protein / GFAP) for the treatment of Alexander disease, a rare autosomal dominant neurodegenerative disease caused by GFAP gene mutations. If approved, zilganersen would become the first FDA-approved therapy for Alexander disease and Ionis's next commercial launch following Wainua (eplontersen) for hereditary transthyretin amyloid polyneuropathy (with the CARDIO-TTransform ATTR-CM primary endpoint miss now behind the company). Zilganersen was granted FDA Fast Track designation and Orphan Drug designation. Alexander disease presents in infancy through adulthood with progressive motor and cognitive decline; no disease-modifying therapies are currently approved. Not a peptide, but the antisense oligonucleotide class continues to complement peptide-based rare-disease therapies (Rein Therapeutics LTI-03 Caveolin-1 peptide for IPF among others) as the RNA modality expands into ultra-orphan indications.
AstraZeneca (NASDAQ: AZN) and Ionis Pharmaceuticals (NASDAQ: IONS) presented Sunday August 30, 2026 at ESC Congress 2026 Munich the detailed subgroup analyses from the Phase 3 CARDIO-TTRansform trial of Wainua (eplontersen, an antisense oligonucleotide targeting transthyretin) in adults with transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). CARDIO-TTRansform did not meet its primary composite endpoint (cardiovascular mortality plus recurrent CV events through 140 weeks) versus placebo. In the prespecified subgroup analysis, patients receiving eplontersen monotherapy achieved a nominally significant hazard ratio of 0.71 versus placebo, while patients on background TTR stabilizer therapy (tafamidis, Vyndaqel/Vyndamax) at baseline showed no treatment effect. The read-out complicates the silencer-plus-stabilizer commercial approach in ATTR-CM that Alnylam's HELIOS-B trial of vutrisiran validated with 28.2% mortality reduction and 32.8% CV event reduction on background tafamidis. AstraZeneca and Ionis will analyze the full dataset to inform next steps in the CARDIO-TTRansform program.