Nusinersen sodium

CARLSBAD, Calif.--(BUSINESS WIRE)--Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) (the “Company”) today reported financial results and provided key updates for the first quarter ended March 31, 2026. “Ionis’ strong performance in the first quarter of 2026 underscores the strength of our commercial and R&D engines. Our independent launches are increasingly contributing to revenue, driven by strong commercial execution, and we are on track for two additional groundbreaking independent launches in 2026 — olezarsen for severe hypertriglyceridemia, our first medicine for a broad patient population, and zilganersen for Alexander disease, the first launch from our leading neurology pipeline,” said Brett P. Monia, Ph.D., chief executive officer of Ionis. “In addition, we look forward to multiple key value-driving events this year, including results from pivotal Phase 3 partnered programs. These include presentation of positive bepirovirsen data in chronic hepatitis B next month at EASL, as well as results from the landmark pelacarsen Lp(a) HORIZON and eplontersen CARDIO-TTRansform cardiovascular outcomes trials later this year.” Three months ended March 31, 2026 2025 (amounts in millions) Total revenue $246 $132 Operating expenses $364 $278 Operating expenses on a non-GAAP basis $321 $249 Loss from operations ($118) ($146) Loss from operations on a non-GAAP basis ($75) ($117) (1) Reconciliation of GAAP to non-GAAP basis contained later in this release. First Quarter 2026 Financial Highlights Revenue increased 87% in the first quarter of 2026 compared to the same period last year, driven by continued commercial success. In addition, Ionis earned substantial R&D revenue, including $95 million in payments from both clinical and regulatory milestones from multiple partnerships Operating expenses for the quarter ended March 31, 2026 were in line with expectations and increased year over year primarily from investments related to the commercialization efforts for TRYNGOLZA and DAWNZERA as well as launch preparations for olezarsen in sHTG and zilganersen in Alexander disease Cash and short-term investments were $1.9 billion as of March 31, 2026. The change in cash and short-term investments from year end 2025 was primarily related to the $633 million the Company used for the maturity of the 0% convertible notes due on April 1, 2026 Increasing annual olezarsen peak net sales guidance to >$3 billion from >$2 billion to reflect increasing confidence in the sHTG market opportunity for olezarsen First Quarter 2026 Financial Results “Ionis entered 2026 with strong momentum. We continued this momentum with the first quarter financial results reflecting increased commercial revenue from our independent launches and robust R&D revenue when compared to the same period last year,” said Elizabeth L. Hougen, chief financial officer of Ionis. “Based on our strong year-to-date revenue performance, accelerating momentum and positive outlook for the rest of the year, we are improving our 2026 financial guidance. The strong performance we expect in 2026 will support substantial growth and long-term value creation and our goal of reaching cash-flow breakeven in 2028.” Recent Highlights - Wholly Owned Medicines TRYNGOLZA ® (olezarsen), the first FDA-approved treatment for adults living with familial chylomicronemia syndrome (FCS) as an adjunct to diet Generated U.S. net product sales of $27 million in the first quarter of 2026, reflecting continued strong demand, offset by a decrease in net price Launch initiated in the European Union (EU) by Sobi Generated U.S. net product sales of $27 million in the first quarter of 2026, reflecting continued strong demand, offset by a decrease in net price Launch initiated in the European Union (EU) by Sobi Olezarsen on track to launch this year as a transformational medicine for severe hypertriglyceridemia (sHTG), assuming approval sNDA accepted by the FDA for Priority Review for the treatment of sHTG with a Prescription Drug User Fee Act (PDUFA) target action date of June 30, 2026 The European Medicines Agency (EMA) accepted an indication extension application in March for the treatment of adult patients with sHTG sNDA accepted by the FDA for Priority Review for the treatment of sHTG with a Prescription Drug User Fee Act (PDUFA) target action date of June 30, 2026 The European Medicines Agency (EMA) accepted an indication extension application in March for the treatment of adult patients with sHTG DAWNZERA™ (donidalorsen), the first and only RNA-targeted prophylactic therapy for hereditary angioedema (HAE) in patients 12 years of age and older Generated U.S. net product sales of $16 million in the first quarter of 2026, an increase of 125% versus the fourth quarter of 2025 Launch initiated in the EU by Otsuka Positive one-year results from OASISplus open-label extension cohort published in the Journal of Asthma and Allergy Generated U.S. net product sales of $16 million in the first quarter of 2026, an increase of 125% versus the fourth quarter of 2025 Launch initiated in the EU by Otsuka Positive one-year results from OASISplus open-label extension cohort published in the Journal of Asthma and Allergy Zilganersen on track to launch this year as the first and only medicine to demonstrate clinically meaningful and disease-modifying benefit in children and adults with Alexander disease (AxD), assuming approval New Drug Application (NDA) for AxD accepted by FDA for Priority Review with PDUFA target action date of September 22, 2026 Expanded access program (EAP) underway Positive additional results from the pivotal study presented at the American Academy of Neurology 2026 annual meeting New Drug Application (NDA) for AxD accepted by FDA for Priority Review with PDUFA target action date of September 22, 2026 Expanded access program (EAP) underway Positive additional results from the pivotal study presented at the American Academy of Neurology 2026 annual meeting Recent Highlights – Partnered Medicines SPINRAZA ® (nusinersen) for the treatment of spinal muscular atrophy (SMA) generated global sales of $374 million in the first quarter of 2026, resulting in royalty revenue of $44 million SPINRAZA high dose regimen approved and launched in the U.S. and EU SPINRAZA high dose regimen approved and launched in the U.S. and EU WAINUA ® (eplontersen) (WAINZUA in EU) for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN) generated global sales of $51 million in the first quarter of 2026, resulting in royalty revenue of $11 million Launches underway in numerous regions, including the EU and China; submissions in progress to expand WAINUA access globally Phase 3 CARDIO-TTRansform study design and baseline characteristics to be presented at the Annual Congress of the Heart Failure Association of the ESC 2026 Launches underway in numerous regions, including the EU and China; submissions in progress to expand WAINUA access globally Phase 3 CARDIO-TTRansform study design and baseline characteristics to be presented at the Annual Congress of the Heart Failure Association of the ESC 2026 Bepirovirsen, a potential first-in-class medicine for chronic hepatitis B (CHB), achieved the primary endpoint demonstrating a statistically significant and clinically meaningful functional cure rate in the B-Well 1 and B-Well 2 Phase 3 studies GSK to present the positive Phase 3 data at the European Association for the Study of the Liver (EASL) Congress 2026 On track for a 2026 launch with global regulatory filings underway, assuming approval NDA filing accepted by FDA for Priority Review with PDUFA date of October 26, 2026; granted Breakthrough Therapy designation Accepted for regulatory review in EU, Japan, and China GSK to present the positive Phase 3 data at the European Association for the Study of the Liver (EASL) Congress 2026 On track for a 2026 launch with global regulatory filings underway, assuming approval NDA filing accepted by FDA for Priority Review with PDUFA date of October 26, 2026; granted Breakthrough Therapy designation Accepted for regulatory review in EU, Japan, and China Revenue Ionis’ revenue was comprised of the following: Three months ended March 31, 2026 2025 Revenue (amounts in millions) Commercial revenue: Product sales, net: TRYNGOLZA sales, net $ 27 $ 6 DAWNZERA sales, net 16 - Total product sales, net 43 6 Royalty revenue: SPINRAZA royalties 44 48 WAINUA royalties 11 9 Other royalties 3 7 Total royalty revenue 58 64 Other commercial revenue 7 6 Total commercial revenue 108 76 Research and development revenue: Collaborative agreement revenue 120 46 WAINUA joint development revenue 18 10 Total research and development revenue 138 56 Total revenue $ 246 $ 132 Commercial revenue for the first quarter ended March 31, 2026, increased 42%, compared to the same period in 2025. This increase was primarily driven by TRYNGOLZA and DAWNZERA product sales. Higher research and development revenue also contributed to the year-over-year revenue increase including approximately $95 million in milestone payments from multiple partnerships. Operating Expenses Operating expenses for the first quarter ended March 31, 2026, were driven from investments primarily related to commercialization efforts for TRYNGOLZA and DAWNZERA as well as launch preparations for olezarsen in sHTG and zilganersen in Alexander disease. Balance Sheet As of March 31, 2026, Ionis’ cash, cash equivalents and short-term investments decreased to $1.9 billion, compared to $2.7 billion on December 31, 2025. At March 31, 2026, Ionis had an escrow deposit of $633 million, which the Company used for the maturity of its 0% convertible notes due on April 1, 2026. 2026 Financial Guidance Ionis improved its 2026 financial guidance to reflect the strong revenue performance experienced year-to-date and the Company’s outlook for the balance of 2026. Overall, the Company increased total revenue and decreased operating loss both by $75 million. The improvements were driven by Priority Review for TRYNGOLZA, strong first quarter R&D revenue and the anticipated continued success of the Company’s ongoing commercial launches. Full Year 2026 Guidance Previous Guidance New Guidance Total Revenue $800-825 million $875-900 million TRYNGOLZA product sales, net NA $100-110 million DAWNZERA product sales, net NA $110-120 million Operating loss on a non-GAAP basis $500-550 million $425-475 million Cash, cash equivalents and short-term investments >$1.6 billion >$1.6 billion Webcast and Other Updates Management will host a conference call and webcast to discuss Ionis’ first quarter 2026 results at 8:30 a.m. Eastern time on Wednesday, April 29, 2026. Interested parties may access the webcast here. A webcast replay will be available for a limited time at the same address. To access the Company’s first quarter 2026 earnings slides click here. Ionis’ Marketed Medicines INDICATION for TRYNGOLZA® (olezarsen) TRYNGOLZA® (olezarsen) was approved by the U.S. Food and Drug Administration as an adjunct to diet to reduce triglycerides in adults with familial chylomicronemia syndrome (FCS). IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS TRYNGOLZA is contraindicated in patients with a history of serious hypersensitivity to TRYNGOLZA or any of the excipients in TRYNGOLZA. Hypersensitivity reactions requiring medical treatment have occurred. WARNINGS AND PRECAUTIONS Hypersensitivity Reactions Hypersensitivity reactions (including symptoms of bronchospasm, diffuse erythema, facial swelling, urticaria, chills and myalgias) have been reported in patients treated with TRYNGOLZA. Advise patients on the signs and symptoms of hypersensitivity reactions and instruct patients to promptly seek medical attention and discontinue use of TRYNGOLZA if hypersensitivity reactions occur. ADVERSE REACTIONS The most common adverse reactions (incidence >5% of TRYNGOLZA-treated patients and >3% higher frequency than placebo) were injection site reactions, decreased platelet count and arthralgia. Please see full Prescribing Information for TRYNGOLZA. INDICATION for DAWNZERATM (donidalorsen) DAWNZERA™ (donidalorsen) was approved by the U.S. Food and Drug Administration for prophylaxis to prevent attacks of hereditary angioedema (HAE) in adult and pediatric patients 12 years of age and older. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS DAWNZERA is contraindicated in patients with a history of serious hypersensitivity reactions, including anaphylaxis, to donidalorsen or any of the excipients in DAWNZERA. WARNINGS AND PRECAUTIONS Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis, have been reported in patients treated with DAWNZERA. If signs and symptoms of serious hypersensitivity reactions occur, discontinue DAWNZERA and institute appropriate therapy. ADVERSE REACTIONS Most common adverse reactions (incidence ≥ 5%) are injection site reactions, upper respiratory tract infection, urinary tract infection, and abdominal discomfort. Please see full Prescribing Information for DAWNZERA. INDICATION for WAINUA® (eplontersen) WAINUA injection, for subcutaneous use, 45 mg is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. IMPORTANT SAFETY INFORMATION for WAINUA® (eplontersen) WARNINGS AND PRECAUTIONS Reduced Serum Vitamin A Levels and Recommended Supplementation WAINUA leads to a decrease in serum vitamin A levels. Supplement with recommended daily allowance of vitamin A. Refer patient to an ophthalmologist if ocular symptoms suggestive of vitamin A deficiency occur. ADVERSE REACTIONS Most common adverse reactions (≥9% in WAINUA-treated patients) were vitamin A decreased (15%) and vomiting (9%). Please see link to U.S. Full Prescribing Information for WAINUA. For more information about SPINRAZA and QALSODY, visit https://www.spinraza.com/ and https://www.qalsody.com/, respectively. QALSODY is approved under accelerated approval based on reduction in plasma neurofilament light chain (NfL) observed in patients treated with QALSODY. Continued approval may be contingent upon verification of clinical benefit in confirmatory trial(s). 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, financial guidance and the therapeutic and commercial potential of our commercial medicines, additional medicines in development, 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, 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® is a registered trademark of Ionis Pharmaceuticals, Inc. TRYNGOLZA® is a registered trademark of Ionis Pharmaceuticals, Inc. DAWNZERATM is a trademark of Ionis Pharmaceuticals, Inc. AKCEATM is a trademark of Akcea Therapeutics, Inc. TEGSEDITM is a trademark of Akcea Therapeutics, Inc. WAYLIVRATM is a trademark of Akcea Therapeutics, Inc. SPINRAZA® and QALSODY® are registered trademarks of Biogen. WAINUA® is a registered trademark of the AstraZeneca group of companies. IONIS PHARMACEUTICALS, INC. SELECTED FINANCIAL INFORMATION Condensed Consolidated Statements of Operations (In Millions, Except Per Share Data) Three months ended March 31, 2026 2025 (unaudited) Revenue: Commercial revenue: Product sales, net $43 $6 Royalty revenue 58 64 Other commercial revenue 7 6 Total commercial revenue 108 76 Research and development revenue: Collaborative agreement revenue 120 46 WAINUA joint development revenue 18 10 Total research and development revenue 138 56 Total revenue 246 132 Expenses: Cost of sales 3 1 Research, development and patent 210 201 Selling, general and administrative 151 76 Total operating expenses 364 278 Loss from operations (118) (146) Other income (expense): Interest expense related to the sale of future royalties (17) (19) Other income, net 42 18 Loss before income tax expense (93) (147) Income tax expense - - Net loss ($93) ($147) Basic and diluted net loss per share ($0.56) ($0.93) Shares used in computing basic and diluted net loss per share 165 159 IONIS PHARMACEUTICALS, INC. Reconciliation of GAAP to Non-GAAP Basis: Condensed Consolidated Operating Expenses, Loss From Operations, and Net Loss (In Millions) Three months ended March 31, 2026 2025 (unaudited) As reported cost of sales according to GAAP $3 $1 Excluding compensation expense related to equity awards (1) - - Non-GAAP cost of sales $3 $1 As reported research, development and patent expenses according to GAAP $210 $201 Excluding compensation expense related to equity awards (25) (20) Non-GAAP research, development and patent expenses $185 $181 As reported selling, general and administrative expenses according to GAAP $151 $76 Excluding compensation expense related to equity awards (18) (9) Non-GAAP selling, general and administrative expenses $133 $67 As reported operating expenses according to GAAP $364 $278 Excluding compensation expense related to equity awards (43) (29) Non-GAAP operating expenses $321 $249 As reported loss from operations according to GAAP ($118) ($146) Excluding compensation expense related to equity awards (43) (29) Non-GAAP loss from operations ($75) ($117) As reported net loss according to GAAP ($93) ($147) Excluding compensation expense related to equity awards and related tax effects (43) (29) Non-GAAP net loss ($50) ($118) (1) Amounts appear as zero due to rounding in millions. Reconciliation of GAAP to Non-GAAP Basis As illustrated in the Selected Financial Information in this press release, non-GAAP operating expenses, non-GAAP loss from operations, and non-GAAP net loss were adjusted from GAAP to exclude compensation expense related to equity awards and the related tax effects. Compensation expense related to equity awards are non-cash. These measures are provided as supplementary information and are not a substitute for financial measures calculated in accordance with GAAP. Ionis reports these non-GAAP results to better enable financial statement users to assess and compare its historical performance and project its future operating results and cash flows. Further, the presentation of Ionis’ non-GAAP results is consistent with how Ionis’ management internally evaluates the performance of its operations. IONIS PHARMACEUTICALS, INC. Condensed Consolidated Balance Sheets  (In Millions) March 31, December 31, 2026 2025 (unaudited) Assets: Cash, cash equivalents and short-term investments $1,919 $2,677 Escrow deposits 633 - Contracts receivable 74 66 Other current assets 312 247 Property, plant and equipment, net 142 123 Right-of-use assets 235 239 Other assets 135 172 Total assets $3,450 $3,524 Liabilities and stockholders’ equity: Current portion of deferred contract revenue $69 $74 0% convertible senior notes due April 2026 – current 433 432 Other current liabilities 215 277 0% convertible senior notes due 2030, net 752 751 1.75% convertible senior notes due 2028, net 569 568 Liability related to sale of future royalties, net 558 551 Long-term lease liabilities 259 262 Long-term obligations, less current portion 28 28 Long-term deferred contract revenue 76 92 Total stockholders’ equity 491 489 Total liabilities and stockholders’ equity $3,450 $3,524 Key 2026 Value Driving Events(1) New Product Launches Program Indication Location DAWNZERA HAE EU Achieved Olezarsen sHTG U.S. Zilganersen Alexander disease U.S. Bepirovirsen CHB U.S. & Japan Regulatory Actions Program Indication Regulatory Action Donidalorsen HAE EU approval decision Achieved Olezarsen sHTG U.S. approval decision EU submission Achieved Zilganersen Alexander disease U.S. submission Achieved U.S. approval decision Nusinersen (high dose) SMA EU approval decision Achieved U.S. approval decision Achieved Eplontersen ATTR-CM Regulatory submission(s) Bepirovirsen HBV Regulatory submission(s) Achieved Regulatory decision(s) Pelacarsen Lp(a)- CVD U.S. submission Key Phase 3 Clinical Events Program Indication Event Obudanersen Angelman syndrome Phase 3 enrollment completion Bepirovirsen HBV B-Well data Achieved Pelacarsen Lp(a)-CVD Lp(a) HORIZON data Eplontersen ATTR-CM CARDIO-TTRansform data Sefaxersen IgAN IMAGINATION data Ulefnersen FUS-ALS FUSION data Salanersen SMA Phase 3 initiation Sapablursen Polycythemia Vera Phase 3 initiation Key Phase 2 Clinical Events Program Indication Event IONIS-MAPTRx/ BIIB080 Alzheimer’s disease Phase 2 CELIA data Tominersen Huntington’s disease Phase 2 GENERATION HD2 data Tonlamarsen Uncontrolled hypertension Phase 2 data Achieved (1) Timing expectations based on current assumptions and subject to change. Indicates that the milestone is anticipated in 2026.

The Medicines and Healthcare products Regulatory Agency (MHRA) has granted marketing authorisation to Biogen for a higher-dose regimen of Spinraza (nusinersen) to treat 5q spinal muscular atrophy (SMA). The updated regimen includes a more rapid loading phase for ‘treatment-naïve’ patients, with two 50mg doses given 14 days apart, followed by 28mg maintenance doses every four months. Patients transitioning from the existing 12mg regimen will receive a single 50mg dose before moving to the same maintenance schedule. SMA is a rare genetic neuromuscular condition affecting around 1,600 people in the UK, with around 70 children born with the condition each year. The most common form, 5q SMA, which accounts for an estimated 95% of cases, is caused by changes in a gene responsible for producing survival motor neuron (SMN) protein. This leads to progressive muscle weakness and loss of movement. Biogen General Manager and Managing Director for the UK and Ireland, Kylie Bromley, said the approval marked “an important milestone for the SMA community”. She added that the firm would continue to work in collaboration with clinicians and patient organisations to improve care, as it had done since Biogen had secured approval for its first SMA treatment in the UK. The decision is supported by data from the phase 2/3 DEVOTE study and its long-term extension, which evaluated the higher-dose regimen in both treatment-naïve patients and those previously treated with the 12mg dose. Across the study, adverse events were consistent with the known safety profile of nusinersen, said the company, with no new safety concerns identified in longer-term follow-up. The most commonly reported events included pneumonia, COVID-19, aspiration pneumonia and malnutrition. Commenting on the approval, Giles Lomax, Chief Executive of Spinal Muscular Atrophy UK, said it ensures continued access to treatment options that can adapt to patients’ changing needs. Mariacristina Scoto, consultant in neuromuscular translational research at Great Ormond Street Hospital for Children, added that the new regimen provides clinicians with additional flexibility when treating patients. The higher-dose regimen is already approved in the US, EU, Switzerland and Japan, with Biogen continuing to work with regulators to expand access globally.