FDA批准Ionis的ZANVASTRO（zilganersen）治疗Alexander病，为该病首个疾病修饰疗法，并授予优先审评券

----- ef20081649_8k.htm -----
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):
September 3, 2026
IONIS PHARMACEUTICALS, INC.
(Exact Name of Registrant as Specified in Charter)
Delaware
(State or Other Jurisdiction of Incorporation)
000-19125
33-0336973
(Commission File No.)
(IRS Employer Identification No.)
2855 Gazelle Court
Carlsbad
,
CA
92010
(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:
☐
Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
☐
Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
☐
Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
☐
Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Securities registered pursuant to Section 12(b) of the Act:
Title of each class
Trading symbol
Name of each exchange on which registered
Common Stock, $.001 Par Value
“
IONS
”
The Nasdaq Stock Market, LLC
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.
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.
Forward-Looking Statements
This report includes forward-looking statements regarding Ionis’ business and the therapeutic and commercial potential of ZANVASTRO, Ionis’ technologies and other
products in development 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, and most recent Form 10-Q, which are 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.
(d)
Exhibits.
Exhibit No.
Description
99.1
Press Release dated September 3, 2026.
104
Cover Page Interactive Data File (embedded within the Inline XBRL document).
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.
Ionis Pharmaceuticals, Inc.
Dated: September 3, 2026
By:
/s/ Patrick R. O’Neil
Patrick R. O’Neil
Executive Vice President, Chief Legal
Officer and General Counsel

----- ef20081649_ex99-1.htm -----
EX-99.1
2
ef20081649_ex99-1.htm
EXHIBIT 99.1
Exhibit 99.1
ZANVASTRO™ (zilganersen) approved by the FDA as the first and only disease modifying treatment for Alexander disease (AxD) in pediatric and adult
patients
- Provides a clinically meaningful impact on motor function and a favorable impact on other symptoms seen in AxD, an ultra-rare, progressive and
often fatal neurological disorder -
- Priority Review Voucher (PRV) awarded in conjunction with approval -
- ZANVASTRO marks Ionis’ first independent launch from its industry-leading neurology pipeline and second independent launch this year –
– Ionis to host webcast on Friday, Sept. 4 at 10:
0
0 a.m. ET –
CARLSBAD, Calif., Sept. 3, 2026 --
Ionis Pharmaceuticals, Inc.
(Nasdaq: IONS) today announced 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. 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 (IT) injection.
“Today’s approval of ZANVASTRO begins a new chapter for people living with Alexander disease and their families, who have long faced this relentlessly progressive and
often fatal disease with no treatment options,” said Brett P. Monia, Ph.D., chief executive officer, Ionis. “This transformative approval also marks our first independent launch from our industry-leading neurology pipeline and underscores the power
of our RNA-targeted technology to address serious neurological diseases without adequate treatment options. We are proud to bring this important new treatment to this incredible community and are deeply grateful to the clinical trial participants
and their families, regulators, investigators and advocates who helped make this advancement possible.”
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.
“For decades, care for people living with Alexander disease has focused primarily on managing symptoms, without an option to modify the underlying cause of disease,” said
Amy Waldman, M.D., M.S.C.E., pediatric neurologist and lead investigator for the ZANVASTRO study at Children’s Hospital of Philadelphia. “The approval of ZANVASTRO for the treatment of Alexander disease represents a significant advancement in care
and opens new possibilities for patients and their families. For the first time, we can move beyond managing individual manifestations of the disease to addressing its underlying biology, with the potential to meaningfully improve outcomes for this
community.”
“As a mom to a young boy living with Alexander disease and an advocate for this community, I have seen firsthand the profound impact this disease has on individuals and
their families. Today’s approval represents a fundamental shift, changing the conversation from ‘How do we manage this disease’ to ‘How can we treat it,’” said Emily Petty, president, End Alexander Disease. “For far too long, receiving a diagnosis
of Alexander disease was accompanied by uncertainty and the difficult reality that there were no available treatments. Today, that begins to change. ZANVASTRO marks a defining moment and brings a new sense of possibility to our community.”
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
(10MWT), 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 (GMFM-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 (AEs) being mild or moderate in severity. Serious treatment-emergent adverse
events (TEAEs) occurred less frequently in the ZANVASTRO group compared to control.
Ionis is committed to helping people access the medicines they are prescribed and will offer a full suite of services for people prescribed ZANVASTRO through Ionis Every
Step™. As part of Ionis Every Step, patients will have access to a wide range of support and resources including disease state and product education for patients and caregivers, access to a dedicated Patient Education Manager, assistance with the
insurance approval process, information on affordability programs and other ongoing services and resources throughout the treatment journey. Visit
ZANVASTRO.com
for more information.
With the approval of ZANVASTRO, the FDA granted Ionis a Rare Pediatric Disease Priority Review Voucher (PRV), 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.
Webcast
Ionis will hold a webcast on Friday, Sept. 4 at 10:00 a.m. ET to discuss the FDA approval. Interested parties may access the webcast
here
. A webcast replay will
be available for a limited time.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Aseptic Meningitis
If symptoms consistent with aseptic meningitis develop, diagnostic workup and treatment should be initiated according to the standard of care.
Adverse reactions of aseptic meningitis (also called chemical meningitis or drug-induced aseptic meningitis) were reported in patients treated with ZANVASTRO during the
double-blind and open-label periods of Study 1. One patient experienced a serious adverse reaction of aseptic meningitis during the double-blind treatment period of Study 1, which reoccurred in the open-label extension period and required dose
interruption and pretreatment with intravenous dexamethasone prior to subsequent administration of ZANVASTRO. Despite corticosteroid premedication, CSF white blood cell (WBC) and protein increased with continued exposure, but the patient remained
asymptomatic and did not require discontinuation from treatment. In addition, nonserious adverse drug reactions of CSF WBC increases have also been reported with ZANVASTRO.
ADVERSE REACTIONS
Most common adverse reactions (incidence
≥
25% patients treated with ZANVASTRO and greater than
control) were vomiting, back pain, cough, headache, and post-lumbar puncture syndrome.
Patients Less Than 2 Years of Age
The adverse reactions of patients less than 2 years of age are expected to be similar to that of pediatric patients 2 years of age and older.
Please see full
Prescribing Information
for ZANVASTRO.
About the ZANVASTRO 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 ZANVASTRO 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 week 60, eligible participants entered a 60-week open-label treatment period, followed by a 120-week open-label long-term extension period. During the long-term extension, participants in the 25 mg dose cohort transitioned to the 50 mg
dose cohort. Participants in countries where zilganersen has not been or is not commercially available can continue to receive zilganersen treatment through a 240-week extended long-term extension period, which includes 20 additional doses,
followed by a 28-week post-treatment follow-up period. The primary endpoint was 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 Alexander Disease (AxD)
AxD is an ultra-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 including support of neurons and oligodendrocytes, which maintain the myelin sheath around 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.
About ZANVASTRO
TM
(zilganersen)
ZANVASTRO
TM
(zilganersen)
is approved by the U.S. Food and Drug
Administration (FDA) for the treatment of Alexander disease (AxD) in pediatric and adult patients. ZANVASTRO is an RNA-targeted therapy designed to inhibit production of excess glial fibrillary acidic protein (GFAP) that accumulates as a result of
pathogenic variants in the
GFAP
gene. For more information about ZANVASTRO, visit
ZANVASTRO.com
.
About Ionis Neurology
Ionis has been at the forefront of discovering and developing leading neurological disease medicines, including ZANVASTRO
TM
(zilganersen), the only approved
treatment for Alexander disease, 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 seven 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 and multiple system atrophy, as well as more common conditions like Alzheimer’s disease.
About Ionis Pharmaceuticals, Inc.
For more than 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 ZANVASTRO, Ionis’ technologies and other
products in development 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, and most recent Form 10-Q, which are 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 registered trademark of Ionis Pharmaceuticals, Inc. ZANVASTRO
TM
and Ionis Every Step
TM
are trademarks of
Ionis Pharmaceuticals, Inc. QALSODY
®
and SPINRAZA
®
are registered trademarks of Biogen. WAINUA
®
is a registered trademark of the AstraZeneca group of companies.
Ionis Investor Contact:
D. Wade Walke, Ph.D.
IR@ionis.com
760-603-2331
Ionis Media Contact:
Hayley Soffer
media@ionis.com
760-603-4679
###