Pelacarsen

iStock, spukkato Ulefnersen, an RNA-targeted therapy being developed by Ionis Pharmaceuticals and Otsuka Pharmaceutical, improved measurements of functional impairment and survival in patients with a rare, genetic ALS subtype in a Phase 3 trial. The partners plan to approach the FDA with the results to determine potential pathways for approval. Three and a half years after Biogen and Ionis Pharmaceuticals won approval for Qalsody to treat a genetic form of ALS, Ionis with partner Otsuka Pharmaceutical is back with another clinical win that could offer hope to patients with a different subtype of the disease. Ulefnersen, an antisense oligonucleotide therapy, showed a statistically significant improvement versus placebo in functional impairment and survival in 73 patients with a genetic subtype of ALS caused by mutations in the fused in sarcoma (FUS) gene, meeting the Phase 3 FUSION trial ’s primary objective. “Ulefnersen is the first therapy to demonstrate a statistically significant benefit in a placebo-controlled study targeting FUS-ALS,” William Blair said in a Tuesday note to investors. The companies plan to discuss the results with the FDA and other global regulators to determine potential pathways for expedited approval. FUS-ALS is an extremely rare form of the neurodegenerative disease, occurring in an estimated 0.6% of cases, according to Otsuka and Ionis’ press release on Tuesday. It affects a broad range of people, including children, and can progress rapidly, the partners said. FUS mutations are more prevalent in juvenile and pediatric ALS, they added, accounting for an estimated 43–52% of cases. Otsuka in November 2024 paid Ionis $10 million upfront for exclusive global rights to ulefnersen. The FUSION study assessed functional impairment and survival after 72 weeks using a joint rank analysis of the ALS Functional Rating Scale Revised (ALSFRS-R), time to rescue and survival without the assistance of a ventilator, tracked from baseline to day 505, according to Otsuka’s Tuesday press release . “The results provide additional evidence that Ionis’s antisense technology can successfully target the underlying genetic drivers of neurodegenerative disease and translate target engagement into meaningful clinical outcomes,” William Blair said. ALS Biogen’s targeted ALS treatment is reversing decline in some patients. Can more be helped? Three years after Qalsody was approved by the FDA as the first drug to target a genetic cause of ALS, some patients are reporting not only disease stabilization but also improvement of symptoms. August 10, 2026 · 7 min read · Heather McKenzie Read more Aside from hitting its primary endpoint, the Phase 3 FUSION trial revealed statistically significant improvements favoring ulefnersen on secondary endpoints, Otsuka said, including change from baseline in serum neurofilament light chain (NfL)—a well-accepted biomarker of neurodegeneration—and time to earliest of death, permanent ventilation, rescue or withdrawal due to disease progression. Ulefnersen had a favorable safety and tolerability profile, with most adverse events being mild or moderate in severity, according to Otsuka and Ionis. “These groundbreaking results offer hope for the FUS-ALS community and represent an exciting milestone in our efforts to transform the treatment of this rare, rapidly progressive and fatal form of genetic ALS,” Holly Kordasiewicz, chief development officer at Ionis, said in a prepared statement on Tuesday. William Blair, meanwhile, called the results “a meaningful validation of Ionis Pharmaceuticals’ RNA-targeted medicines platform and a notable achievement for the company’s precision neurology strategy.” It’s been a mixed bag for Ionis lately, but the company’s neurology portfolio appears to be gaining momentum. The biotech is set to launch its first independent neurology drug after the FDA approved its antisense oligonucleotide therapy Zanvastro earlier this month as the first disease-modifying treatment for Alexander disease. Approvals FDA approves Ionis’ antisense drug as first targeted therapy for Alexander disease Zanvastro, an antisense oligonucleotide therapy, represents the first independent neurology launch for Ionis Pharmaceuticals, which intends to leverage the foothold for more approvals in rare neurodegenerative diseases, including Angelman syndrome. September 3, 2026 · 5 min read · Heather McKenzie Read more BMO Capital Markets also noted the Alexander approval, writing in a Tuesday evening note that the FUSION study “provides further validation of Ionis’ ASO platform following the approval of Zanvastro . . . which is much needed after recent setbacks for eplontersen and pelacarsen.” Eplontersen (Wainua), on which Ionis is partnered with AstraZeneca, caused a considerable stir in the transthyretin-mediated amyloid cardiomyopathy (ATTR-CM) space when the antisense drug—which is FDA approved for polyneuropathy associated with hereditary ATTR— failed to show efficacy in a Phase 3 ATTR-CM trial in July. Pelacarsen, partnered with Novartis, showed no significant benefit on cardiovascular risk earlier this month in the Phase 3 Lp(a)HORIZON study . Ionis’ stock has dropped nearly 50% since before the Wainua readout. However, the biotech rebounded again on Wednesday as sefaxersen—licensed by Roche—met its primary endpoint in the Phase III IMAgINATION study , significantly reducing a kidney disease marker in patients with primary IgA nephropathy (IgAN). The ALS space has similarly faced its fair share of setbacks. Most recently, Novartis last week revealed it has halted development of lifonebart, a TREM2 stabilizer for the neurodegenerative disease after the asset failed to meet either the primary or secondary endpoints in the Phase 2 ASTRALS trial. Prior to that, in 2024, Amylyx announced that Relyvrio —approved by the FDA in Sept. 2022— failed the confirmatory PHOENIX trial, showing no significant difference compared to placebo on functional impairment in ALS. The company subsequently pulled Relyvrio from the U.S. and Canadian markets. That news closely followed the Phase 2 failure of Sanofi and Denali’s RIPK1 inhibitor SAR443820/DNL788 in the HIMALAYA study . But Biogen and Ionis’ antisense ALS drug Qalsody, approved in April 2023 for ALS associated with mutations in the superoxide dismutase 1 (SOD1) gene, has been a notable outlier. The drug is showing real-world efficacy , with some patients reporting not only disease stabilization but also an improvement of symptoms.