Ionis’ antisense drug stabilizes ultra-rare disease ahead of FDA decision

 

The pivotal study of zilganersen in Alexander disease missed a secondary endpoint, but analysts expect the FDA to approve the asset given the unmet need and overall data.

Ionis Pharmaceuticals shared more data Tuesday on its ultra-rare disease drug prospect zilganersen, providing more evidence of efficacy amid preparations for the biotech’s first independent launch in neurology.

In September, Ionis reported that its investigational antisense oligonucleotide significantly improved gait stability in a pivotal Phase 1–3 study in Alexander disease (AxD), achieving the primary endpoint. AxD is a rare neurological disease that affects about 300 people in the U.S., Kyle Jenne, Ionis’ chief global product strategy officer, said during the company’s 2025 earnings call in February. The FDA accepted Ionis’ filing for priority review last month.

Researchers presented more data from the trial at the American Academy of Neurology annual meeting, showing “statistically and clinically meaningful stabilization of motor function” and a consistent trend toward benefit across key secondary endpoints.

The previously reported 33.3% increase in gait speed over placebo in the 10-meter walk test at week 61 reflected stabilization in the zilganersen cohort and declining performance in the control arm, William Blair analysts said in a Tuesday note to investors.

Secondary endpoints favored zilganersen, although the molecule’s effect on patients’ most bothersome symptom (MBS) fell short. The MBS—which was not disclosed—improved in 42.1% of patients taking the study drug and worsened in 56.3% of people on placebo, but the result was not statistically significant.

William Blair analysts said the MBS miss likely drove nominal statistical significance in the Patient Global Impression of Change, a self-assessment of a patient’s condition. The miss may have implications for the FDA review, though “We believe FDA regulatory flexibility will be at play, especially around which key secondary endpoint the agency will anchor to, given the miss on MBS,” the firm said.

Despite the missed secondary endpoint, the analysts said they are confident the FDA will approve the drug by the Sept. 22 deadline. This position reflects the high unmet need in AxD and the consistent improvements in health outcomes compared to placebo in the clinical trial. Zilganersen is the first investigational medicine to demonstrate a disease-modifying impact in AxD, according to the company’s September 2025 press release.

William Blair forecasts peak zilganersen sales of $295 million in AxD, while Jenne said on Ionis’ earnings call that the biotech expects more than $100 million in peak sales for the program. Focusing on about a dozen centers, Ionis plans to launch the drug with a very modest-sized team, Jenne added. Ionis will partner zilganersen outside the U.S., CEO Brett Monia said during an investor event in February.

Capabilities established to commercialize zilganersen could give Ionis a launchpad for bringing more neurology products to market. Ionis expects to report Phase 3 data on obudanersen for the treatment of Angelman syndrome next year and to launch the product in 2028. Citing a 2016 study, Ionis said in its February business update that the condition affects more than 100,000 people in major geographies.

https://www.biospace.com/drug-development/ionis-antisense-drug-stabilizes-ultra-rare-disease-ahead-of-fda-decision