Olezarsen Sodium

Plozasiran led to an 80% median reduction in baseline of fasting triglyceride level in a Phase III trial. Image credit: Shutterstock/ peterschreiber.media. The US Food and Drug Administration (FDA) has accepted a new drug application (NDA) for Arrowhead Pharmaceutical’s plozasiran in the same indication, a month after the first treatment was approved by the regulator for the treatment of familial chylomicronemia syndrome (FCS). The Prescription Drug User Fee Act (PDUFA) action date for Arrowhead’s candidate is 18 November 2025, with the FDA adding that it currently does not intend to hold an advisory committee meeting. FCS is a rare metabolic disease that prevents the body from breaking down fats due to a mutation in lipoprotein lipase. The resulting elevated levels of triglycerides can lead to chronic abdominal pain, diabetes, hepatic steatosis, and acute and potentially fatal pancreatitis. Arrowhead’s NDA is supported by data from the Phase III PALISADE (NCT04998201) trial, along with supportive confirmatory evidence from Phase II studies in the SUMMIT programme. Plozasiran lowered triglyceride levels and reduced acute pancreatitis risk, leading the trial to meet primary and all multiplicity-controlled key secondary endpoints. Plozasiran is an RNA interference (RNAi) therapeutic that cuts the production of apolipoprotein C-III (APOC3), a key regulator of triglyceride metabolism. Last month, Ionis Pharmaceuticals’ Tryngolza (olezarsen) became the first treatment approved for FCS by the FDA. Similar to plozasiran, Tryngolza is also an RNA-based drug designed to reduce the body’s production of APOC3. Direct comparisons between the two drugs have not been made in clinical trials. High-dose Tryngolza led to a 44% placebo-adjusted drop in triglyceride levels from baseline at six months, with this rising to 59% in months six to 12. For 25mg plozasiran, the median reduction in baseline fasting triglyceride level was 80%. Tryngolza is forecast to generate $303m in annual revenue by 2030, according to GlobalData’s Pharma Intelligence Center. GlobalData is the parent company of Pharmaceutical Technology . Arrowhead’s CEO Chris Anzalone said: “We are laser-focused on our ongoing work to ensure an efficient and successful commercial launch this year, pending FDA review and approval.” In addition to targeting FDA approval, Arrowhead stated that it intends to submit applications for plozasiran in FCS treatment to additional regulatory authorities this year. The pharma company also has further lipid-based plans for plozasiran and is investigating the drug in severe hypertriglyceridemia and mixed hyperlipidemia. Moreover, Arrowhead placed a target on the obesity treatment space by advancing two RNAi-based candidates to clinic in August 2024.

– Accelerating value creation with numerous commercial, regulatory and pipeline milestones – – Ionis outlines clear path to sustained positive cash flow – CARLSBAD, Calif., Jan. 13, 2025 /PRNewswire/ -- Ionis Pharmaceuticals, Inc. (Nasdaq: IONS) today announced highlights from the Company's 2024 achievements and previewed important milestones expected in 2025. Ionis will provide a business update at the 42nd Annual J.P. Morgan Healthcare Conference on Wednesday, January 15 at 10:30am PT; the presentation is available today on the Ionis website. "With last month's U.S. approval and launch of TRYNGOLZA™ (olezarsen) as the first-ever therapy for familial chylomicronemia syndrome and the potential approval of donidalorsen in hereditary angioedema later this year, Ionis has entered a new chapter as a fully integrated commercial-stage biotechnology company that independently brings our innovative medicines to patients," said Brett P. Monia, Ph.D., chief executive officer, Ionis. "TRYNGOLZA is the first of four independent Ionis product launches anticipated over the next three years. We also expect four key launches from important partnered programs within this timeframe. Collectively, these medicines stand to help millions of patients with serious diseases and create substantial value for all our stakeholders. To that end, we expect increasing product and royalty revenue to enable Ionis to achieve our goal of being cash flow positive." 2025 Anticipated Highlights Include: Launch TRYNGOLZA, Ionis' first independent product and the first-ever therapy for U.S. patients with familial chylomicronemia syndrome (FCS): U.S. Food and Drug Administration (FDA) Approval for FCS on December 19, 2024 Potential European Medicines Agency (EMA) approval for FCS Phase 3 results and U.S. regulatory submission for olezarsen in severe hypertriglyceridemia, a large patient population with high unmet need Phase 3 topline data for CORE, CORE 2 and ESSENCE Phase 3 trials expected in second half of 2025 Potential approval of donidalorsen, a first-in-class RNA-targeted medicine for hereditary angioedema and Ionis' second anticipated independent launch: U.S. FDA action date of August 21, 2025 U.S. commercial field team scale-up and launch Continue progress with WAINUA™ (eplontersen), Ionis' first U.S. co-commercialized medicine in collaboration with AstraZeneca: Continued positive performance in U.S. launch for polyneuropathy of hereditary transthyretin-mediated amyloidosis (ATTRv-PN) OUS approvals for ATTRv-PN Continuing the fully enrolled, landmark CARDIO-TTRansform trial in ATTR cardiomyopathy, with data expected in the second half of 2026 Advance the next wave of wholly owned medicines for serious neurological diseases, including seven clinical-stage therapies: Phase 3 trial start in first half of 2025 for ION582 for Angelman syndrome Phase 3 data for zilganersen in Alexander disease, a rare leukodystrophy with no approved disease-modifying therapies Phase 2 data for ION464 (SNCA) in multiple system atrophy Continue momentum with key partnered programs, including: Phase 3 data for pelacarsen, a potentially groundbreaking medicine for Lp(a)-driven cardiovascular disease (Novartis) Continue advancing next-generation technologies for RNA-targeted medicines Achieve clinical proof of concept for Mesyl Phosphoramidate (MsPA) backbone and siRNA platforms Advance first Bicycle-siRNA into clinical development Select first clinical candidate engineered to cross the blood brain barrier 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 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 U.S. Full Prescribing Information for WAINUA. About Ionis Pharmaceuticals, Inc. For three decades, Ionis has invented medicines that bring better futures to people with serious diseases. Ionis currently has six marketed medicines and a leading pipeline in neurology, cardiology, and other 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 TRYNGOLZA, Ionis' technologies and other products in development. 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 but not limited to those related to our commercial products and the medicines in our pipeline, and particularly 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 Dec. 31, 2023, and most recent Form 10-Q, which are on file with the SEC. Copies of these and other documents are available at . Ionis Pharmaceuticals® and TRYNGOLZA™ are trademarks of Ionis Pharmaceuticals, Inc. WAINUA™ is a registered trademark of the AstraZeneca plc. Ionis Investor Contact: D. Wade Walke, Ph.D. [email protected] 760-603-2331 Ionis Media Contact: Hayley Soffer [email protected] 760-603-4679 SOURCE Ionis Pharmaceuticals, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED