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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.

ARLINGTON, Va., Sept. 22, 2026 /PRNewswire/ -- The ALS Association celebrates today's news that ulefnersen, an investigational antisense therapy for people with FUS-ALS, met its primary endpoint in the Phase 3 FUSION trial. Ulefnersen is now the second antisense therapy, after Qalsody (tofersen) for SOD1-ALS, to show it can change the course of a genetic form of ALS, raising hope that this approach can be used to treat more types of the disease. The ALS Association was an early funder of antisense research in ALS, taking a chance on the technology two decades ago, before it had ever been tried in neurodegenerative disease. The drug's developers, Otsuka and Ionis, reported that ulefnersen significantly improved a combined measure of function and survival compared to placebo, with supporting results on key secondary measures and a favorable safety profile. This is the first placebo-controlled trial to show that targeting the genetic cause of FUS-ALS can change the course of the disease. FUS-ALS is rare, but it is the most common cause of juvenile ALS, and it often progresses quickly in young people. Until now, these families have had no treatment designed for them. "Today's results happened because of an amazing young woman named Jaci Hermstad, her family and a community that refused to accept that a rare form of ALS was too rare to treat," said Calaneet Balas, president and CEO of the ALS Association. "We are fighting for families affected by this especially cruel type of ALS and we hope today's news provides encouragement. We are proud that ALS Association donors helped make the early work possible, and we will keep pushing for a fast, thorough regulatory review." Jaci Hermstad was a young woman living with FUS-ALS whose advocacy helped launch the research, and for whom the drug was first named jacifusen. When the early clinical work at Columbia University ran short of resources, the ALS Association partnered with Project ALS to fund it, and later supported the expanded access program led by Columbia's Dr. Neil Shneider that treated additional people with FUS-ALS. Those early results, including one participant who regained the ability to walk and breathe on her own, helped pave the way for the global Phase 3 trial. Today, we are thinking of Jaci, who died in 2020, and of her family. Her courage in facing this disease, and her determination to help others who would come after her, made this day possible. Ulefnersen is not yet approved. The ALS Association urges Otsuka, Ionis, and the FDA to move with the urgency these results demand, including priority review and broad access for people living with FUS-ALS while the therapy is under review. We will continue to advocate for timely access and will share updates with the community as they become available. About the ALS Association The ALS Association is the largest philanthropic funder of ALS research in the world. The Association funds global research collaborations, assists people with ALS and their families through its nationwide network of care and certified clinical care centers, and advocates for better public policies for people with ALS. The ALS Association is working to make ALS a livable disease while urgently searching for new treatments and a cure. For more information about the ALS Association, visit our website at als.org. About ALS Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. Over the course of the disease, people lose the ability to move, to speak, and eventually, to breathe. The disease is always fatal, usually within five years of diagnosis. Few treatment options exist, resulting in a high unmet need for new therapies to address functional deficits and disease progression. SOURCE The ALS Association 21% more press release views with Request a Demo