[8-K] Ionis Pharmaceuticals, Inc. Reports Material Event

Rhea-AI Filing Summary

Ionis Pharmaceuticals reported positive topline results from the pivotal Phase 3 CORE and CORE2 studies of olezarsen in severe hypertriglyceridemia (sHTG). Across nearly 1,100 patients required to remain on standard-of-care lipid-lowering therapy, olezarsen produced highly statistically significant, placebo-adjusted mean reductions in fasting triglycerides of up to 72% and a highly statistically significant 85% reduction in acute pancreatitis events. Both 80 mg and 50 mg monthly doses met the primary endpoint at six months with strong p-values (p<0.0001), and the company described safety and tolerability as favorable.

Positive

• Up to 72% placebo-adjusted mean reduction in fasting triglycerides at six months
• 85% reduction in acute pancreatitis events reported
• Large pivotal program with nearly 1,100 patients on standard-of-care therapy
• Both 80 mg and 50 mg monthly doses met the primary endpoint with p<0.0001
• Company reports favorable safety and tolerability

Negative

• None.

Insights

Clinical Development Specialist

TL;DR: Phase 3 CORE/CORE2 show large triglyceride reductions and fewer pancreatitis events, supporting olezarsen's clinical efficacy.

The pivotal program enrolled nearly 1,100 patients on background lipid-lowering therapy, strengthening applicability to treated sHTG populations. Both monthly doses (80 mg and 50 mg) achieved highly statistically significant placebo-adjusted triglyceride reductions at six months (up to 72% difference) with accompanying 85% reduction in acute pancreatitis events. Safety and tolerability are described as favorable, which is critical for chronic therapy but full safety data are not included in this report.

Biopharma Financial Analyst

TL;DR: Positive pivotal results materially de-risk clinical program and could affect valuation if corroborated by full data and regulatory plans.

Demonstrated large, statistically robust triglyceride lowering and a substantial reduction in pancreatitis events across a large pivotal population are commercially meaningful outcomes for sHTG. The requirement that patients remained on standard-of-care therapy during trials supports an additive effect. The company labels safety as favorable; however, the 8-K provides topline metrics only, so full datasets, event rates, and subgroup analyses will be needed to assess durability, safety signals, and potential regulatory timelines.

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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):  September 2, 2025

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 2, 2025, Ionis Pharmaceuticals, Inc.  (“Ionis,” “we,” “us” or “our company”) issued a press release announcing positive topline results from the pivotal Phase 3 CORE and CORE2 studies of olezarsen in people with severe hypertriglyceridemia (“sHTG”).  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 2, 2025, we announced positive topline results from the pivotal Phase 3 CORE and CORE2 studies of olezarsen in people with sHTG. In the studies, olezarsen demonstrated a highly statistically significant placebo-adjusted mean reduction in fasting triglycerides of up to 72% and a highly statistically significant reduction in acute pancreatitis events of 85% with favorable safety and tolerability. CORE and CORE2 make up the largest pivotal program for sHTG, with nearly 1,100 patients who were required to be on standard of care lipid-lowering therapy throughout the treatment period.

The CORE and CORE2 studies met the primary endpoint, with both 80 mg and 50 mg monthly doses of olezarsen demonstrating a highly statistically significant placebo-adjusted mean reduction in fasting triglyceride levels at six months:

	Olezarsen 80 mg	Olezarsen 50 mg	Placebo
CORE
Percent reduction from baseline1	73%	63%	0.5%
Percent placebo-adjusted reduction2	72%	63%
P-value3	p<0.0001	p<0.0001
CORE2
Percent reduction from baseline1	68%	63%	14%
Percent placebo-adjusted reduction2	55%	49%
P-value3	p<0.0001	p<0.0001

1. Least-squares mean. 2. Least-squares mean difference of percent reduction in fasting triglycerides. 3. P-values are based on comparison between each olezarsen group and placebo group in percent reduction in fasting triglycerides.

Additionally, the studies met the secondary endpoint of reduction in acute pancreatitis events. Olezarsen demonstrated a highly statistically significant 85% reduction in events (p=0.0002) compared to placebo. This was a prespecified analysis of pooled olezarsen groups compared to pooled placebo groups across both studies at 12 months.

Olezarsen demonstrated a favorable safety and tolerability profile. Adverse events were generally balanced across treatment groups, and serious adverse events occurred less frequently in the olezarsen groups compared to placebo. Injection site reactions, which were mostly mild, were the most common adverse event and occurred more frequently in the olezarsen groups compared to placebo. More than 90% of patients who completed CORE and CORE2 chose to continue into the open-label extension study.

We plan to submit a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration by end of year. Detailed data will be presented at an upcoming medical conference.

Forward-Looking Statements

Certain statements contained in this report are forward-looking statements that involve a number of risks and uncertainties. Such forward-looking statements include, without limitation, statements regarding Ionis’ business, the therapeutic and commercial potential of olezarsen, our commercial medicines, additional medicines in development and technologies, and Ionis’ expectations regarding development and regulatory milestones. Words such as “anticipate,” “believe,” “could,” “continue,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, though not all forward-looking statements necessarily contain these identifying words. For such statements, Ionis claims the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995. Actual events or results may differ materially from Ionis’ expectations. Factors that could cause actual results to differ materially from the forward-looking statements include, but are not limited to, 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. Additional factors that could cause actual results to differ materially from those stated or implied by Ionis’ forward-looking statements are disclosed in Ionis’ filings with the Securities and Exchange Commission, including in the section captioned “Risk Factors” in Ionis’ most recent Annual Report on Form 10-K and subsequently filed Quarterly Reports on Form 10-Q. These forward-looking statements represent Ionis’ judgment as of the time of this report. Ionis disclaims any intent or obligation to update these forward-looking statements, other than as may be required under applicable law.

Item 9.01 Financial Statements and Exhibits.

(d) Exhibits.

Exhibit No.	Description
99.1	Press Release dated September 2, 2025.
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 2, 2025		By:	/s/ Patrick R. O’Neil
			Patrick R. O’Neil
			Executive Vice President, Chief Legal Officer and General Counsel

FAQ

What topline results did Ionis (IONS) report for olezarsen in the Phase 3 CORE and CORE2 studies?

Ionis reported highly statistically significant placebo-adjusted mean reductions in fasting triglycerides of up to 72% and a highly statistically significant 85% reduction in acute pancreatitis events.

How many patients were enrolled across CORE and CORE2?

The CORE and CORE2 programs included nearly 1,100 patients in the pivotal program.

Which olezarsen doses met the primary endpoint and what were the results?

Both 80 mg and 50 mg monthly doses met the primary endpoint at six months. Reported placebo-adjusted triglyceride reductions were up to 72% (80 mg) and 55% (50 mg) with p<0.0001 versus placebo.

Were patients allowed to stop their lipid-lowering therapy during the trials?

No. Patients were required to remain on standard-of-care lipid-lowering therapy throughout the treatment period.

What does the filing say about safety?

The 8-K states that olezarsen had favorable safety and tolerability, but the filing provides topline statements rather than full safety datasets.