Ionis Pharmaceuticals, Inc.

Item 7.01 Regulation FD Disclosure. On September 3, 2026, Ionis Pharmaceuticals, Inc. (“Ionis”) issued a press release announcing that the U.S. Food and Drug Administration (“FDA”) has approved ZANVASTRO™ (zilganersen) for the treatment of Alexander disease (“AxD”) in pediatric and adult patients. A copy of the press release is furnished as Exhibit 99.1 to this Current Report on Form 8-K. The information in this Item 7.01 and the exhibit attached hereto shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, regardless of any general incorporation language in such filing.

Item 8.01 Other Events. On September 3, 2026, Ionis announced that the U.S. FDA has approved ZANVASTRO™ (zilganersen) for the treatment of AxD in pediatric and adult patients. ZANVASTRO is the first and only disease modifying treatment for AxD, an ultra-rare, progressive and often fatal neurological disorder that can affect motor, cognitive, autonomic and gastrointestinal function. Until now, treatment of AxD has primarily been limited to managing symptoms. ZANVASTRO is an RNA-targeted medicine designed to address the underlying disease mechanism of AxD by reducing the production of glial fibrillary acidic protein (“GFAP”). ZANVASTRO 50 mg is administered quarterly as an intrathecal injection. AxD affects approximately 1 in 1 to 3 million people worldwide. Initial signs of AxD can present from infancy through adulthood and may vary depending on age of onset. As AxD progresses, symptoms may include progressive motor and cognitive dysfunction, a loss of independence and the inability to control muscles for swallowing, airway protection and purposeful movements. AxD is caused by changes in the GFAP gene that lead to the overproduction and toxic accumulation of GFAP in astrocytes. Over time, dysfunction in astrocytes can damage neurons and myelin, which can lead to symptoms commonly associated with AxD. The FDA approval was based on positive results from the pivotal study of ZANVASTRO in people living with AxD. The pivotal study met its primary endpoint in individuals ≥ 5 years of age, with ZANVASTRO 50 mg demonstrating statistically significant and clinically meaningful stabilization of gait speed as assessed by the 10-Meter Walk Test, a commonly used measure of gross motor function in neurologic disease, compared to control at Week 61 (least square mean difference 33.3%, p=0.041). ZANVASTRO also demonstrated improvement in gross motor function in patients 2 to 4 years of age as assessed by the Gross Motor Function Measure-88, a well-established motor endpoint, compared to control at Week 61. Secondary and exploratory endpoint results from patient/caregiver- and clinician-reported outcome assessments consistently favored ZANVASTRO. ZANVASTRO demonstrated a favorable safety and tolerability profile, with most adverse events being mild or moderate in severity. Serious treatment-emergent adverse events occurred less frequently in the ZANVASTRO group compared to control. With the approval of ZANVASTRO, the FDA granted Ionis a Priority Review Voucher, a program designed to incentivize the development of therapies for serious and life-threatening diseases by providing a mechanism to potentially accelerate regulatory review timelines for subsequent applications. ZANVASTRO will be available in the U.S. in the coming weeks. In June 2026, Ionis entered into a license agreement with Recordati, a global pharmaceutical company headquartered in Italy, focused on specialty and rare diseases, under which Recordati obtained exclusive rights to develop and commercialize zilganersen in all countries outside the U.S. Ionis is working closely with Recordati on preparing regulatory submissions in Europe and Japan, which are expected in 2027.