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iStock, Rocco-Herrmann 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. Ionis Pharmaceuticals is set to launch its first independent neurology drug after the FDA signed off on Zanvastro, formerly zilganersen, as the first disease-modifying treatment for an ultrarare genetic condition called Alexander disease. The approval, which came more than two weeks before its Sept. 22 PDUFA date, is the first therapy to directly target the protein buildup that drives Alexander disease, or AxD. “For patients with Alexander disease and their families, there have been no approved treatment options—only supportive care while the disease progresses,” Emily Freilich, director of the Division of Neurology I in the FDA’s Center for Drug Evaluation and Research (CDER) said in a statement alongside the FDA’s announcement, adding that the approval is a “landmark moment” for the AxD community. Alexander disease is an extremely rare leukodystrophy, affecting as few as one in 3 million people worldwide. It is caused by changes in the GFAP gene that lead to its overproduction and toxic accumulation in glial cells in the central nervous system. Over time, this dysfunction can damage neurons and myelin, leading to symptoms including motor and cognitive dysfunction, a loss of independence and the inability to control muscles for swallowing, airway protection and purposeful movements. AxD can begin in childhood or later in life. In early onset cases, “You’ll have kiddos that are developing normally, then they begin to show symptoms, and then they’ll have a decline and a degeneration that happens, and it’s almost always fatal,” Holly Kordasiewicz, head of Development at Ionis, told BioSpace last month prior to the approval. “It’s a really tough disease.” An antisense oligonucleotide (ASO), Zanvastro works by binding to the RNA to decrease the body’s production of the GFAP protein, explained Amy Waldman, medical director of the Leukodystrophy Center and a pediatric neurologist at Children’s Hospital of Philadelphia. Zanvastro met the primary endpoint in Ionis’ pivotal Phase 3 trial, which tested the therapy in 49 patients who were at least 5 years old, according to Ionis. Participants given a 50-mg dose of Zanvastro saw statistically significant and clinically meaningful stabilization of gait speed as assessed by the 10-meter walk test—a commonly used measure of motor function in neurologic disease—compared to those received no treatment at week 61. “A flat line in a degenerative disease and not have that progression is really remarkable,” Kordasiewicz said. A separate open label substudy tested Zanvastro in four patients less than 2 years of age. As walking speed is not a “reliable measure of progress” in children this age, the FDA said, a broader motor skills assessment including standing, walking, running, and jumping was deployed. In this group, “children treated with Zanvastro showed improvement on this measure while those in the control group declined,” according to the release. Zanvastro is approved for patients of all ages with AxD. “To see improvement, that they’re allowing some of that neurodevelopment to happen in those earlier ages because we’ve stopped this, that was really exciting,” Kordasiewicz said. Despite the positive data, Waldman, who is the lead investigator on Ionis’ pivotal Phase 3 trial, offered a more subdued perspective. With rare leukodystrophies like AxD, she said, stability is the ultimate goal. “Families really want patients to improve, and they want something to be cured, and they want the brain to heal in the different ways,” she told BioSpace . “But really, stability is what we’re trying to do and slow down disease progression. We don’t expect to reverse permanent neurologic damage.” Approvals Ionis secures market expansion for Tryngolza as FDA clears severe hypertriglyceridemia use The approval of Ionis Pharmaceuticals’ Tryngolza for severe hypertriglyceridemia could spur “substantial growth” for the product, according to William Blair. June 25, 2026 · 2 min read · Tristan Manalac Read more A new chapter for Ionis Zanvastro is Ionis’ second independent launch this year, after the biotech notched what William Blair called a “major market expansion” in June for another ASO, Tryngolza , in severe hypertriglyceridemia. Tryngolza was initially approved in 2024 as the first treatment for familial chylomicronemia syndrome, a rare, life-threatening disease. Ionis has a deep history in neurology. In 2016, the biotech, along with Biogen, won approval for Spinraza, the first FDA‑approved treatment for spinal muscular atrophy. Then, in April 2023, the longtime partners secured the FDA’s nod for Qalsody , just the fourth-ever therapy for amyotrophic lateral sclerosis (ALS) and the first to treat a genetic form of the disease. “We’ve been in this space for a long time, but we haven’t launched any of our own medicines in neurology,” Kordasiewicz said. When Brett Monia took over as CEO in 2020, Ionis started to build and launch its own commercial products and building out a commercial infrastructure, she added. While the biotech had already accomplished this feat in the cardiovascular space with Tryngolza, Ionis had not yet secured that position in neurology—until Thursday. “This [approval] gives us a footprint in neurology out there in the community,” Kordasiewicz told BioSpace last month. The launch of Zanvastro will also help to prepare Ionis for independent neurology approvals to come, she added, including in Angelman syndrome, where the company is conducting the Phase 3 REVEAL study . Also an RNA-based therapy, obudanersen is designed to inhibit the expression of the UBE3A antisense transcript and increase production of UBE3A protein, whose function is lost in Angelman. Angelman syndrome is another rare, neurodegenerative disease—and a difficult one to target. Ultragenyx crashed on Thursday after reporting the previous day that its own ASO for the disease, apazunersen, failed to improve cognition in a Phase 3 trial. While Ionis shares were also down 3% in post-market trading on Wednesday following Ultragenyx’s announcement, William Blair expressed confidence in obudanersen, writing in a note to investors on Wednesday that Ionis’ Phase I/II HALOS trial results “leaves us confident that obudanersen could elicit signal in Angelman where insufficient dosing from apazunersen could not.” REVEAL is expected to read out in August 2027, per ClinicalTrials.gov. For now, Ionis—and the Alexander disease community—can celebrate a landmark win. Rare diseases Ultragenyx’s ‘high-risk’ Angelman bet fails, cratering stock and forcing strategic review The success of apazunersen in a Phase 3 trial for Angelman syndrome was a key driver of Ultragenyx’s value, according to William Blair, and the asset’s failure robs the biotech of any meaningful near-term milestones. September 3, 2026 · 2 min read · Tristan Manalac Read more

iStock, Yutthana Gaetgeaw Safety and dosing are likely to be “key differentiators” for Arrowhead Pharmaceuticals as it looks to challenge Ionis Pharmaceuticals’ lead in the severe hypertriglyceridemia market. Arrowhead Pharmaceuticals’ touted placebo-like safety for its RNA interference therapy plozasiran in two late-stage studies of severe hypertriglyceridemia—but analysts are left conflicted over the assets competitive prospects., Detailed late-stage results “are favorable and arguably support a best-in-class profile” for plozasiran, Stifel wrote in a Sunday note. Plozasiran is currently approved as Redemplo for familial chylomicronemia syndrome, a rare genetic disease that causes high triglyceride levels. Meanwhile, BMO Capital Markets on Monday favored the currently commercially available choice, Ionis Pharmaceuticals’ antisense oligonucleotide Tryngolza. In the Phase 3 SHASTA-3 and SHASTA-4 trials, total treatment-emergent adverse events (TEAE) were similar between plozasiran and placebo arms, but serious TEAEs only occurred in 8.3% of patients on plozasiran versus 10% on placebo comparators. The detailed safety data were presented Sunday at the European Society of Cardiology’s 2026 meeting in Munich, and could support a supplemental FDA submission to expand Redemplo into severe hypertriglyceridemia, a filing that Arrowhead said is planned for later this year. Stifel zeroed in on safety and dosing, which it argued “are really the key differentiators here” versus Tryngolza, which snagged approval for severe hypertriglyceridemia in December 2024. Arrowhead’s plozasiran is meant to be dosed once every three months, while Tryngolza is a monthly injection. Rare diseases Arrowhead puts pressure on Ionis with positive data for triglyceride lowering drug With Phase 3 data showing what analysts called a “potentially best-in-class profile,” Arrowhead Pharmaceuticals plans to submit for FDA approval of plozasiran by the end of the year—hoping to follow to market Ionis Pharmaceuticals’ Tryngolza, which got the regulator’s nod in severe hypertriglyceridemia last month. July 22, 2026 · 2 min read · Heather McKenzie Read more In particular, the firm pointed to the absence of anaphylaxis or hypersensitivity reactions with plozasiran as compared with an approximate 7% rate of “possible” hypersensitivity events for Tryngolza. There were also no meaningful liver enzyme elevations with plozasiran—a safety event that according to Stifel was documented in around 7% of patients on Tryngolza. Of note, however, Arrowhead reported three deaths in plozasiran-treated patients—two cardiovascular deaths and one linked to chronic myelomonocytic leukemia—though none were deemed related to the study drug. BMO, on the other hand, focused on the worsening glycemic control observed in 14.3% of patients on plozasiran, as per Arrowhead’s Sunday announcement—a signal that could potentially affect “positioning among patients with comorbid diabetes.” Ionis’ drug has the edge here, the analysts continued, which in turn “may provide a modest competitive advantage” for Tryngolza. On the efficacy front, Sunday’s readouts for SHASTA-3 and SHASTA-4 were “consistent” with topline data shared last month , showing median triglyceride reductions of 79% and 81%, respectively, after a year. In both cases, the therapeutic effect was statistically significant. Around 750 patients were enrolled across SHASTA-3 and SHASTA-4. Plozasiran’s triglyceride-lowering effect was stronger in those with baseline levels at least 880 mg/dL. In this subgroup, median triglyceride reduction hit 85%. SHASTA-3 and SHASTA-4 also found that 52% and 55% of patients on plozasiran reached triglyceride levels below 150 mg/dL at 12 months, respectively, versus 7.9% and 2% of placebo comparators. Pre-specified analyses also found that across both late-stage studies, plozasiran reduced acute pancreatitis (AP) events by 78% versus placebo, an effect that appeared stronger in those with higher baseline triglyceride levels and who had any prior AP history. In all, Stifel believes that the SHASTA data “support a differentiated safety profile” for plozasiran, “which, with Q3M dosing, should position ARWR/plozasiran to be best-in-class.” There are no head-to-head studies directly comparing plozasiran with Tryngolza, and Stifel concedes that the severe hypertriglyceridemia market “is big enough for multiple significant products.”