Pivotal zilganersen data boost Ionis (NASDAQ: IONS) ahead of FDA PDUFA
Filing Impact
Filing Sentiment
Form Type
8-K
Rhea-AI Filing Summary
Ionis Pharmaceuticals reported additional positive results from its pivotal Phase 1-3 study of zilganersen in Alexander disease, a rare and often fatal neurological disorder with no approved disease‑modifying treatments. In patients aged ≥5, zilganersen 50 mg met the study’s primary endpoint by stabilizing gait speed on the 10‑Meter Walk Test at Week 61 versus control, showing a 33.3% least‑square mean difference (p=0.041). In children aged 2‑4, Gross Motor Function Measure‑88 results suggested improved gross motor function versus control. Multiple patient, caregiver and clinician‑reported secondary endpoints generally favored zilganersen, and an exploratory analysis showed a 33.6% reduction in plasma GFAP levels at Week 61 versus control. Safety was described as favorable, with serious treatment‑emergent adverse events less frequent than in the control group. Zilganersen is under FDA Priority Review with a Prescription Drug User Fee Act action date of September 22, 2026.
Positive
- Pivotal efficacy achieved in Alexander disease: Zilganersen 50 mg met the primary endpoint in patients ≥5 years by stabilizing gait speed on the 10‑Meter Walk Test at Week 61 versus control, with a 33.3% least‑square mean difference (p=0.041), in an indication with no approved disease‑modifying therapies.
- Regulatory momentum with Priority Review: Zilganersen is under U.S. FDA Priority Review for Alexander disease, with a Prescription Drug User Fee Act action date set for September 22, 2026, signaling regulatory focus on a high‑unmet‑need, rare neurological condition.
Negative
- None.
Insights
Pivotal AxD data support zilganersen ahead of a 2026 FDA decision.
Ionis released detailed pivotal data for zilganersen in Alexander disease. The drug met its primary endpoint in patients aged ≥5, with a 33.3% least‑square mean difference in gait speed on the 10‑Meter Walk Test at Week 61 (p=0.041). Younger children showed supportive gains on the GMFM‑88 scale.
Patient, caregiver and clinician assessments generally favored zilganersen, and an exploratory analysis found a 33.6% reduction in plasma GFAP levels at Week 61 versus control, aligning with the RNA‑targeted mechanism. Serious treatment‑emergent adverse events were less frequent with zilganersen than control, indicating a favorable tolerability profile in this small, severely affected population.
Zilganersen is under FDA Priority Review with a PDUFA action date of September 22, 2026, and has Breakthrough Therapy, Orphan Drug and Rare Pediatric Disease designations. Future regulatory outcomes and longer‑term open‑label data from the ongoing extension period will further clarify its role in Alexander disease.
8-K Event Classification
3 items: 7.01, 8.01, 9.01
3 items
Item 7.01
Regulation FD Disclosure
Disclosure
Material non-public information disclosed under Regulation Fair Disclosure, often investor presentations or guidance.
Item 8.01
Other Events
Other
Voluntary disclosure of events the company deems important to shareholders but not covered by other items.
Item 9.01
Financial Statements and Exhibits
Exhibits
Financial statements, pro forma financial information, and exhibit attachments filed with this report.
Key Figures
PDUFA action date: September 22, 2026
Primary endpoint effect: 33.3% least-square mean difference
GMFM-88 improvement: 22.9-point difference
+5 more
8 metrics
PDUFA action date
September 22, 2026
FDA Priority Review for zilganersen in Alexander disease
Primary endpoint effect
33.3% least-square mean difference
Gait speed on 10-Meter Walk Test at Week 61, patients ≥5 years, p=0.041
GMFM-88 improvement
22.9-point difference
Gross motor function in children 2-4 years at Week 61, nominal p=0.034
Plasma GFAP reduction
33.6% decrease
Exploratory analysis at Week 61 vs pooled control, nominal p=0.003
Serious TEAEs zilganersen
37.5%
Serious treatment-emergent adverse events with zilganersen 25 mg or 50 mg
Serious TEAEs control
47.1%
Serious treatment-emergent adverse events in pooled control group
Study duration
60 weeks double-blind
Randomized controlled treatment period before open-label extension
Participants in pivotal study
54 participants
Global Phase 1-3 study of zilganersen in Alexander disease
Key Terms
Priority Review, PDUFA action date, Gross Motor Function Measure-88 (GMFM-88), 10-Meter Walk Test (10MWT), +2 more
6 terms
Priority Review regulatory
"Zilganersen is currently under Priority Review by the U.S. Food and Drug Administration"
Priority review is a regulatory fast-track that shortens the time an agency spends evaluating a drug, vaccine or medical device application so a decision comes sooner than normal. For investors, it matters because a faster review is like an express lane to market: it can speed revenue potential and reduce regulatory uncertainty, but it does not guarantee approval and still requires the product to meet safety and effectiveness standards.
PDUFA action date regulatory
"with a Prescription Drug User Fee Act action date of September 22, 2026"
A PDUFA action date is the deadline the U.S. Food and Drug Administration sets for completing its review of a drug or biologic application under the Prescription Drug User Fee Act. Think of it as a project completion date for a new medicine: the agency’s decision by that date — approval, rejection, or a request for more data — can quickly change a company’s revenue prospects, risk profile, and stock value, so investors monitor it closely.
Gross Motor Function Measure-88 (GMFM-88) medical
"New data from the Gross Motor Function Measure-88 (GMFM-88), a well-established motor endpoint"
Gross Motor Function Measure-88 (GMFM-88) is a standardized clinical test made up of 88 tasks that assesses large, everyday movements—such as lying down, sitting, standing and walking—primarily in children with movement disorders. Investors care because it is a widely accepted way to show whether a therapy, medical device or rehabilitation program produces real, measurable improvements in mobility; strong GMFM-88 results can support regulatory approval, market adoption and sales forecasts.
10-Meter Walk Test (10MWT) medical
"stabilization of gait speed as assessed by the 10-Meter Walk Test (10MWT), compared to control at Week 61"
A 10-meter walk test measures how quickly a person walks a straight 10-meter distance, usually timed with a stopwatch to calculate walking speed. Investors should care because it is a simple, objective clinical outcome often used in drug and device trials to show real-world improvement in mobility and independence—think of it like timing how fast someone walks down a hallway to judge whether a treatment truly helps them move better.
Breakthrough Therapy regulatory
"The U.S. Food and Drug Administration (FDA) granted zilganersen Breakthrough Therapy, Orphan Drug and Rare Pediatric Disease designations"
A breakthrough therapy is a regulatory designation granted to an experimental drug or treatment when early clinical evidence indicates it could offer a substantial improvement over existing options for a serious or life‑threatening condition. For investors it matters because the label brings faster, more intensive interaction with regulators and can shorten development and review time—like a VIP fast‑track toward potential approval, reducing time and risk before a product can reach the market.
Rare Pediatric Disease designation regulatory
"FDA granted zilganersen Breakthrough Therapy, Orphan Drug and Rare Pediatric Disease designations"
A rare pediatric disease designation is an official regulatory status given to a drug or therapy that targets a serious or life‑threatening condition primarily affecting children and is uncommon in the population. It matters to investors because the status often brings financial and development perks — such as tax credits, reduced fees, faster review and periods of market protection — which can lower costs, speed approval and improve the commercial outlook; think of it as a VIP pass that makes bringing a scarce, child‑focused treatment to market easier and potentially more profitable.
UNITED STATES SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
PURSUANT TO SECTION 13 OR 15(d) OF THE
SECURITIES EXCHANGE ACT OF 1934
Date of report (Date of earliest event reported): April 21, 2026
(Exact Name of Registrant as Specified in Charter)
(State or Other Jurisdiction of Incorporation)
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(Address of Principal Executive Offices and Zip Code)
Registrant’s telephone number, including area code: (760 ) 931-9200
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following
provisions:
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Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
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Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
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Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
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Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
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Securities registered pursuant to Section 12(b) of the Act:
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Title of each class
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Name of each exchange on which
registered
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (Section 230.405 of this chapter) or
Rule 12b-2 of the Securities Exchange Act of 1934 (Section 240.12b-2 of this chapter).
Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised
financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
| Item 7.01 |
Regulation FD Disclosure.
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On April 21, 2026, Ionis Pharmaceuticals, Inc. (“Ionis,” “we,” “us” or “our company”) issued a press release announcing additional positive results from the pivotal study of zilganersen in children and adults living with Alexander disease (“AxD”). 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.
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On April 21, 2026, we announced additional positive results from the pivotal study of zilganersen in children and adults living with AxD,
a rare, progressive and often fatal neurological condition with no approved disease-modifying treatments. These findings, which will be presented today at the 2026 American Academy of Neurology annual meeting, build on previously reported positive
topline data and provide a more comprehensive view of treatment effect across multiple clinically meaningful domains.
The study met its primary endpoint in individuals ≥5 years of age, with zilganersen 50 mg demonstrating statistically significant and clinically meaningful stabilization
of gait speed as assessed by the 10-Meter Walk Test (10MWT), compared to control at Week 61. The 10MWT is a commonly used measure of gross motor function in neurologic disease. New data from the Gross Motor Function Measure-88 (GMFM-88), a
well-established motor endpoint, supports the primary outcome of the study by demonstrating that treatment with zilganersen may improve gross motor function in younger children (2-4 years of age), compared to control. Key secondary endpoint results
from patient/caregiver-and clinician-reported outcome assessments consistently favored zilganersen. Zilganersen demonstrated favorable safety and tolerability.
AxD is a rare, genetic, progressive and often fatal neurological condition that is primarily associated with toxic over-production of glial fibrillary acidic protein (“GFAP”). It is estimated to occur in approximately 1 per 1 to 3 million people worldwide. Although symptoms vary depending on age of onset, individuals may
experience progressive motor and cognitive dysfunction, a loss of independence and the inability to control muscles for swallowing, airway protection and purposeful movements. Zilganersen is an investigational RNA-targeted medicine designed to
reduce overproduction of GFAP, the underlying cause of AxD.
Zilganersen Pivotal Study Results
The pivotal Phase 1-3 study of zilganersen included 53 people with AxD aged 2 to 53 years. Results presented today are from the 60-week double-blind, randomized
controlled treatment period of the ongoing trial. Zilganersen met the primary endpoint in patients ≥5 years, resulting in statistically significant and clinically meaningful
stabilization of gait speed on the 10MWT at Week 61 compared to control (least square mean difference 33.3%, p=0.041). Additionally, results from the GMFM-88 in children 2-4 years of age support that zilganersen may improve gross motor function at
Week 61 compared to control (least square mean difference 22.9 points, nominal1 p=0.034).
1 Nominal p-value; statistical analysis was not controlled for multiplicity
Key secondary endpoints favored zilganersen over control:
Key secondary endpoints evaluated the disease’s heterogeneous presentation through assessments focused on the individual’s most bothersome AxD symptom and their overall
health. Across these measures, outcomes favored zilganersen-treated individuals, with more reporting improvement or no change and fewer reporting worsening compared to control.
| • |
Most Bothersome Symptom:
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In the zilganersen group, 32% of patients rated their most bothersome symptom as “much better” compared to 0% on control. Only 5% of patients receiving
zilganersen rated their most bothersome symptom as “much worse” compared to 31% on control.
| • |
Patient Global Impression of Severity:
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In the zilganersen group, 83% of patients reported improvement or no change in overall disease severity compared to 76% on control. Only 17% of
patients receiving zilganersen reported worsening compared to 24% on control.
| • |
Patient Global Impression of Change:
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In the zilganersen group, 21% of patients reported feeling “much better” overall compared to 0% on control. Only 4% of patients receiving zilganersen
reported feeling “much worse” compared to 18% on control.
| • |
Clinical Global Impression of Change:
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Clinicians rated 75% of patients receiving zilganersen as improved (“a little better”) or “no change” compared to 47% on control. Clinicians rated 25% of patients receiving zilganersen as “a little worse” and 0% as “much worse” compared to 41% as “a little worse” and 12% as “much worse” on control.
Results from additional secondary and exploratory endpoints assessing communication, swallowing, gastrointestinal and autonomic symptoms, support that zilganersen may
have a positive impact across AxD symptoms.
In an exploratory analysis, zilganersen reduced plasma GFAP levels by 33.6% at Week 61 compared to control (nominal1 p=0.003)2, consistent with its
mechanism of targeting GFAP RNA in the central nervous system.
Zilganersen demonstrated a favorable safety and tolerability profile, with most adverse events mild or moderate in severity. Serious treatment-emergent adverse events
occurred less frequently in the zilganersen group compared to control (37.5% zilganersen 25 mg or 50 mg; 47.1% pooled control).
Zilganersen is currently under Priority Review by the U.S. Food and Drug Administration with a Prescription Drug User Fee Act action date of September 22, 2026.
2 Ratio (zilganersen vs. pooled control) of least-squares geometric mean ratio to baseline 0.664
Forward-Looking Statements
This report includes forward-looking statements regarding Ionis’ business and the therapeutic and commercial potential of zilganersen, our commercial medicines,
additional medicines in development and technologies and our expectations regarding development and regulatory milestones. Any statement describing Ionis’ goals, expectations, financial or other projections, intentions or beliefs is a
forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties including those inherent in the process of discovering, developing and commercializing medicines that are safe
and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis’ forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to
differ materially from those expressed or implied by such forward-looking statements. Although Ionis’ forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known
by Ionis. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis’
programs are described in additional detail in Ionis’ annual report on Form 10-K for the year ended December 31, 2025, which is on file with the Securities and Exchange Commission. Copies of these and other documents are available from Ionis.
| Item 9.01 |
Financial Statements and Exhibits.
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(d) Exhibits.
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Exhibit No.
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Description
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99.1
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Press Release dated April 21, 2026.
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Cover Page Interactive Data File (embedded within the Inline XBRL document).
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SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, as amended, the registrant has duly caused this report to be signed on its
behalf by the undersigned, thereunto duly authorized.
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Ionis Pharmaceuticals, Inc.
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Dated: April 21, 2026
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By: | /s/ Patrick R. O’Neil |
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Patrick R. O’Neil
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Executive Vice President, Chief Legal Officer and General Counsel
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Exhibit 99.1
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FINAL: April 20, 2026
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Ionis presents new data from pivotal study of zilganersen in Alexander disease (AxD) at AAN 2026 Annual Meeting
– New data highlight potential treatment benefit across multiple AxD symptom domains,
reinforcing zilganersen’s positive impact on people living with this rare, often fatal
neurological disease –
– PDUFA date set for September 22, 2026 –
CARLSBAD, Calif., April 21, 2026 -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced additional positive results from the pivotal study of zilganersen in children and adults living with
Alexander disease (AxD), a rare, progressive and often fatal neurological condition with no approved disease-modifying treatments. These findings, which will be presented today at the 2026 American Academy of Neurology (AAN) annual meeting, build
on previously reported positive topline data and provide a more comprehensive view of treatment effect across multiple clinically meaningful domains.
The study met its primary endpoint in individuals ≥5 years of age, with zilganersen 50 mg demonstrating statistically significant and clinically meaningful
stabilization of gait speed as assessed by the 10-Meter Walk Test (10MWT), compared to control at Week 61. The 10MWT is a commonly used measure of gross motor function in neurologic disease. New data from the Gross Motor Function Measure-88
(GMFM-88), a well-established motor endpoint, supports the primary outcome of the study by demonstrating that treatment with zilganersen may improve gross motor function in younger children (2-4 years of age), compared to control. Key secondary
endpoint results from patient/caregiver-and clinician-reported outcome assessments consistently favored zilganersen. Zilganersen demonstrated favorable safety and tolerability.
“As a clinician who cares for people living with Alexander disease, I see firsthand the profound and progressive impact this disease has on individuals and
their families, particularly given the lack of disease modifying treatment options available today,” said Amy Waldman, M.D., pediatric neurologist and lead investigator for the zilganersen study at Children’s Hospital of Philadelphia. “These
results mark a meaningful step forward for families who have waited so long for innovation in Alexander disease. Taken together, the consistent pattern across multiple clinically meaningful measures demonstrates that zilganersen has the potential
to change the trajectory of this devastating disease.”
AxD is a rare, genetic, progressive and often fatal neurological condition that is primarily associated with toxic over-production of glial fibrillary acidic
protein (GFAP). It is estimated to occur in approximately 1 per 1 to 3 million people worldwide. Although symptoms vary depending on age of onset, individuals may experience progressive motor and cognitive dysfunction, a loss of independence and
the inability to control muscles for swallowing, airway protection and purposeful movements. Zilganersen is an investigational RNA-targeted medicine designed to reduce overproduction of GFAP, the underlying cause of AxD.
Zilganersen Pivotal Study Results
The pivotal Phase 1-3 study of zilganersen included 53 people with AxD aged 2 to 53 years. Results presented today are from the 60-week double-blind,
randomized controlled treatment period of the ongoing trial. Zilganersen met the primary endpoint in patients ≥5 years, resulting in statistically significant and
clinically meaningful stabilization of gait speed on the 10MWT at Week 61 compared to control (least square mean difference 33.3%, p=0.041). Additionally, results from the GMFM-88 in children 2-4 years of age support that zilganersen may improve
gross motor function at Week 61 compared to control (least square mean difference 22.9 points, nominal1 p=0.034).
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FINAL: April 20, 2026
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Key secondary endpoints favored zilganersen over control:
Key secondary endpoints evaluated the disease’s heterogeneous presentation through assessments focused on the individual’s most bothersome AxD symptom and
their overall health. Across these measures, outcomes favored zilganersen-treated individuals, with more reporting improvement or no change and fewer reporting worsening compared to control.
| • |
Most Bothersome Symptom (MBS):
|
In the zilganersen group, 32% of patients rated their most bothersome symptom as “much better” compared to 0% on control. Only 5% of
patients receiving zilganersen rated their most bothersome symptom as “much worse” compared to 31% on control.
| • |
Patient Global Impression of Severity (PGIS):
|
In the zilganersen group, 83% of patients reported improvement or no change in overall disease severity compared to 76% on control. Only
17% of patients receiving zilganersen reported worsening compared to 24% on control.
| • |
Patient Global Impression of Change (PGIC):
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In the zilganersen group, 21% of patients reported feeling “much better” overall compared to 0% on control. Only 4% of patients receiving
zilganersen reported feeling “much worse” compared to 18% on control.
| • |
Clinical Global Impression of Change (CGIC):
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Clinicians rated 75% of patients receiving zilganersen as improved (“a little better”) or “no change” compared to 47% on control. Clinicians rated 25% of patients receiving zilganersen as “a little worse” and 0% as “much worse” compared to 41% as “a little worse” and 12% as “much worse” on control.
Results from additional secondary and exploratory endpoints assessing communication, swallowing, gastrointestinal and autonomic symptoms, consistently
support that zilganersen may have a positive impact across AxD symptoms.
In an exploratory analysis, zilganersen reduced plasma GFAP levels by 33.6% at Week 61 compared to control (nominal1 p=0.003)2,
consistent with its mechanism of targeting GFAP RNA in the central nervous system.
“These data further build on the promise of zilganersen and reinforce its potential to help transform the treatment landscape for people living with
Alexander disease,” said Holly Kordasiewicz, Ph.D., executive vice president, chief development officer, Ionis. “The zilganersen results underscore the strength of our technology in targeting the underlying cause of disease, even in complex and
heterogenous neurological conditions such as Alexander disease. We are deeply grateful to the patients, families, investigators and broader community who made this research possible. As we look ahead to the FDA action date in September, we remain
focused on bringing this potential new treatment to a community that has long been underserved.”
1 Nominal p-value; statistical analysis was not controlled for multiplicity
2 Ratio (zilganersen vs. pooled control) of least-squares geometric mean ratio to baseline 0.664
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FINAL: April 20, 2026
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Zilganersen demonstrated a favorable safety and tolerability profile, with most adverse events (AE) mild or moderate in severity. Serious treatment-emergent
adverse events (TEAEs) occurred less frequently in the zilganersen group compared to control (37.5% zilganersen 25 mg or 50 mg; 47.1% pooled control).
Zilganersen is currently under Priority Review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) action date of
September 22, 2026.
About the Zilganersen Study
The global, multicenter, randomized, double-blind, controlled, multiple-ascending
dose (MAD) Phase 1-3 study (NCT04849741) enrolled 54 participants with
Alexander disease (AxD) between the ages of 1.5 and 53 years across 13 sites in eight countries. Most participants in the study were children, reflecting the early onset and severe progression of AxD in pediatric populations. Participants were
randomized in a 2:1 ratio to receive zilganersen or control for a 60-week double-blind treatment period. The study included two dose cohorts, 25 mg and 50 mg, with the 50 mg dose cohort analyzed as the pivotal dose cohort, with dosing every 12
weeks. At 60 weeks, all eligible participants transitioned into an open-label treatment period, followed by a 120-week open-label, long-term extension treatment period, during which participants in the 25 mg dose cohort moved to the 50 mg dose
cohort, and finally a 28-week post-treatment follow-up period. The primary endpoint is percent change from baseline in gait speed as assessed by the 10-Meter Walk Test (10MWT), an assessment of functional mobility, at the end of the double-blind
treatment period. Key secondary endpoints include patients' self-identified Most Bothersome Symptom (MBS) Score, change from baseline in Patient Global Impression of Severity (PGIS) Score and Patient Global Impression of Change (PGIC) Score and
Clinician Global Impression of Change (CGIC) Score at the end of the double-blind treatment period.
About Zilganersen
Zilganersen is an investigational RNA-targeted medicine being evaluated as a treatment for people with Alexander disease (AxD). Zilganersen is designed to
inhibit production of excess glial fibrillary acidic protein (GFAP) that accumulates because of disease-causing variants in the GFAP gene. The U.S. Food and Drug
Administration (FDA) granted zilganersen Breakthrough Therapy, Orphan Drug and Rare Pediatric Disease
designations. In addition, the European Medicines Agency (EMA) granted zilganersen Orphan Drug designation.
About Alexander Disease (AxD)
AxD is a rare, progressive and often fatal neurological disease that occurs in approximately 1 per 1 to 3 million people worldwide and affects a type of cell
in the brain called astrocytes. Astrocytes have multiple roles in the brain to support neurons and oligodendrocytes, including maintenance of the myelin sheath that protects nerve fibers. AxD is caused by disease-causing variants in the glial
fibrillary acidic protein (GFAP) gene and is generally characterized by progressive neurological deterioration resulting in loss of functional mobility, loss of
independence and the inability to control muscles for large movements, swallowing and airway protection, though symptoms can vary depending on age of onset. AxD usually leads to death within 14-25 years after symptom onset. There are no approved
disease-modifying medicines.
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FINAL: April 20, 2026
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About Ionis Neurology
Ionis has been at the forefront of discovering and developing leading neurological disease medicines, including SPINRAZA® (nusinersen), the first
approved treatment for spinal muscular atrophy, WAINUA® (eplontersen), a medicine to treat hereditary transthyretin-mediated amyloid polyneuropathy (ATTRv-PN), and QALSODY® (tofersen) for SOD1-ALS. The clinical-stage portfolio
includes 12 investigational medicines, of which six are wholly owned by Ionis. Ionis' investigational portfolio includes medicines for which there are few or no disease modifying treatments, such as rare diseases including Angelman syndrome, prion
disease, multiple system atrophy, Huntington’s disease and Alexander disease, as well as more common conditions such as Alzheimer's disease.
About Ionis Pharmaceuticals, Inc.
For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has marketed medicines and a
leading pipeline in neurology, cardiometabolic disease and select areas of high patient need. As the pioneer in RNA-targeted medicines, Ionis continues to drive innovation in RNA therapies in addition to advancing new approaches in gene editing. A
deep understanding of disease biology and industry-leading technology propels our work, coupled with a passion and urgency to deliver life-changing advances for patients. To learn more about Ionis, visit Ionis.com and follow us on X (Twitter), LinkedIn and Instagram.
Ionis Forward-looking Statements
This press release includes forward-looking statements regarding Ionis' business and the therapeutic and commercial potential of zilganersen, our commercial
medicines, additional medicines in development and technologies and our expectations regarding development and regulatory milestones. Any statement describing Ionis' goals, expectations, financial or other projections, intentions or beliefs is a
forward-looking statement and should be considered an at-risk statement. Such statements are subject to certain risks and uncertainties including those inherent in the process of discovering, developing and commercializing medicines that are safe
and effective for use as human therapeutics, and in the endeavor of building a business around such medicines. Ionis' forward-looking statements also involve assumptions that, if they never materialize or prove correct, could cause its results to
differ materially from those expressed or implied by such forward-looking statements. Although Ionis' forward-looking statements reflect the good faith judgment of its management, these statements are based only on facts and factors currently known
by Ionis. Except as required by law, we undertake no obligation to update any forward-looking statements for any reason. As a result, you are cautioned not to rely on these forward-looking statements. These and other risks concerning Ionis'
programs are described in additional detail in Ionis' annual report on Form 10-K for the year ended December 31, 2025, which is on file with the Securities and Exchange Commission. Copies of these and other documents are available from the Company.
In this press release, unless the context requires otherwise, "Ionis," "Company," "we," "our" and "us" all refer to Ionis Pharmaceuticals and its subsidiaries.
Ionis Pharmaceuticals® is a trademark of Ionis Pharmaceuticals, Inc. SPINRAZA® and QALSODY® are registered trademarks of Biogen. WAINUA™ is a registered trademark of the
AstraZeneca group of companies.
FAQ
What did Ionis Pharmaceuticals (IONS) report about zilganersen in Alexander disease?
Ionis reported additional positive results from a pivotal Phase 1-3 study of zilganersen in Alexander disease. The drug met its primary endpoint by stabilizing gait speed in patients aged five and older and showed supportive benefits in younger children and multiple symptom domains.
How effective was zilganersen in the pivotal AxD study reported by Ionis (IONS)?
In patients aged five and older, zilganersen 50 mg produced a 33.3% least-square mean difference in gait speed on the 10-Meter Walk Test at Week 61 versus control (p=0.041). Younger children also showed improved gross motor function on the GMFM-88 scale compared with control.
What safety profile did zilganersen show in Ionis’ (IONS) Alexander disease trial?
Zilganersen demonstrated a favorable safety and tolerability profile, with most adverse events mild or moderate. Serious treatment-emergent adverse events occurred less often with zilganersen 25 mg or 50 mg (37.5%) than with pooled control (47.1%) over the 60-week double-blind treatment period.
What regulatory status does zilganersen have according to Ionis (IONS)?
Zilganersen is under U.S. FDA Priority Review with a PDUFA action date of September 22, 2026. It has FDA Breakthrough Therapy, Orphan Drug and Rare Pediatric Disease designations, and Orphan Drug status from the European Medicines Agency for Alexander disease.
How many patients were included in the Ionis (IONS) pivotal zilganersen study?
The pivotal Phase 1-3 study enrolled 54 participants with Alexander disease aged 1.5 to 53 years across 13 sites in eight countries. Fifty-three people contributed to the reported 60-week double-blind, randomized controlled treatment results highlighted in the company’s disclosure.
Did zilganersen impact GFAP levels in Ionis’ (IONS) trial?
In an exploratory analysis, zilganersen reduced plasma glial fibrillary acidic protein (GFAP) levels by 33.6% at Week 61 compared with pooled control (nominal p=0.003). This biomarker reduction is consistent with its RNA-targeted design to decrease excess GFAP production in Alexander disease.