Pelacarsen

Eli Lilly's Lepodisiran Shows 95% Reduction in Lipoprotein(a), Offering New Hope for South Asian Heart Patients

2 months ago

• Eli Lilly's experimental drug lepodisiran demonstrated up to 95% reduction in lipoprotein(a) levels with a single 400mg dose in midstage trials, potentially addressing a significant cardiovascular risk factor prevalent in South Asian populations. • The once-yearly injectable targets LPA cholesterol particles that are found in elevated levels in approximately 25% of South Asians and are not addressed by current cholesterol-lowering medications like statins. • With an estimated 64 million Indians suffering from heart conditions and above-average death rates, lepodisiran represents a targeted intervention that could significantly impact cardiovascular disease management in the region.

Merck Licenses Oral Lipoprotein(a) Inhibitor HRS-5346 from Hengrui Pharma in $1.97 Billion Deal

2 months ago

• Merck has secured exclusive global rights (excluding Greater China) to HRS-5346, an investigational oral small molecule Lipoprotein(a) inhibitor currently in Phase 2 trials in China. • The $1.97 billion deal includes a $200 million upfront payment to Hengrui Pharmaceuticals, with potential milestone payments of up to $1.77 billion plus royalties on net sales. • Elevated Lipoprotein(a), a genetic condition affecting approximately 1.4 billion people worldwide, is an independent risk factor for cardiovascular disease with limited treatment options currently available.

Ionis and Ono Forge $940 Million Deal for Sapablursen in Polycythemia Vera Treatment

2 months ago

• Ionis Pharmaceuticals has licensed sapablursen, an RNA-targeted medicine for polycythemia vera, to Ono Pharmaceutical in a deal worth up to $940 million including $280 million upfront. • Sapablursen, currently in Phase 2 trials, has received FDA Fast Track and Orphan Drug designations and works by increasing hepcidin production to regulate iron homeostasis in PV patients. • Ono will gain exclusive global rights for development and commercialization, while Ionis will complete the ongoing IMPRSSION study before transferring responsibilities.

Novartis Extends Timeline for Pelacarsen Phase 3 Cardiovascular Trial to 2026

4 months ago

• Novartis announces Phase 3 data for pelacarsen, an Lp(a)-lowering antisense therapy, is now expected in first half of 2026, with regulatory submissions planned for second half. • The Lp(a)HORIZON trial, involving over 8,000 patients, aims to be the first cardiovascular outcomes study evaluating Lp(a) reduction's impact on cardiovascular risk. • Developed by Ionis and licensed to Novartis in 2019, pelacarsen targets a significant unmet need affecting over 8 million people worldwide with elevated Lp(a) and cardiovascular disease.

Novartis Focuses on Immunology and Gene Therapies for Future Growth

4 months ago

• Novartis is prioritizing immunology with expectations of multiple Phase II and Phase III readouts in the next five years, signaling a strong pipeline in this area. • The company is expanding its gene therapy capabilities through acquisitions like Kate Biotherapeutics, acquired for $1.1 billion in November 2024. • Novartis is streamlining its portfolio to concentrate on key therapeutic areas, aiming to drive future growth and innovation in specific sectors.

Ionis Pharmaceuticals Advances Neurological and Cardiovascular Therapies with New Clinical Trials and FDA Approvals

4 months ago

Ionis Pharmaceuticals is set to enter a new chapter in 2025, focusing on advancing treatments for serious neurological diseases and cardiovascular conditions. The company has outlined plans for Phase 3 trials for ION582 for Angelman syndrome, zilganersen for Alexander disease, and ION464 for multiple system atrophy. Additionally, Ionis has received FDA approval for TRYNGOLZA™ (olezarsen) to reduce triglycerides in adults with familial chylomicronemia syndrome and for WAINUA™ (eplontersen) for treating polyneuropathy of hereditary transthyretin-mediated amyloidosis.

Ionis' Tryngolza Approved for FCS as Arrowhead's Plozasiran Awaits FDA Review

5 months ago

• The FDA has approved Ionis Pharmaceuticals' Tryngolza (olezarsen) as the first treatment for adults with familial chylomicronemia syndrome (FCS). • Tryngolza, an RNA-targeted therapy, significantly reduces triglyceride levels and the risk of acute pancreatitis in FCS patients when used with a low-fat diet. • Arrowhead Pharmaceuticals' plozasiran, another RNA interference therapeutic for FCS, has been accepted for FDA review, with a decision expected by November 2025. • Clinical trials showed Tryngolza achieved a 57% placebo-adjusted mean reduction in triglycerides at 12 months, while plozasiran demonstrated an 80% median reduction.

Zerlasiran Shows Significant Lipoprotein(a) Reduction in Phase 2 Trial

6 months ago

• Zerlasiran, a novel siRNA, significantly reduced time-averaged lipoprotein(a) levels by over 80% in a Phase 2 trial, offering a potential treatment for elevated Lp(a). • The ALPACAR-360 trial demonstrated the efficacy and safety of zerlasiran with infrequent dosing in patients at high risk of atherosclerotic cardiovascular disease (ASCVD). • The study's findings support the advancement of zerlasiran into Phase 3 trials as a promising gene-silencing approach for individuals with genetically determined high Lp(a) levels. • Common treatment-related adverse effects were mild injection site reactions, with no serious adverse events linked to zerlasiran, highlighting its tolerability.

Lilly's Oral Muvalaplin Significantly Reduces Lipoprotein(a) Levels in Phase II Trial

6 months ago

• Eli Lilly's muvalaplin, an oral drug, significantly reduced lipoprotein(a) (Lp(a)) levels in a Phase II study, meeting the primary endpoint. • The study showed dose-dependent reductions in Lp(a) levels, with the 60 mg and 240 mg doses achieving reductions of 81.7% and 85.8%, respectively. • Muvalaplin's novel mechanism disrupts the interaction between apolipoprotein(a) and apolipoprotein(b), preventing Lp(a) formation. • Current cholesterol-lowering medicines are not approved to lower Lp(a) levels, highlighting muvalaplin's potential to address an unmet need.

Zerlasiran Shows Cumulative Lp(a) Reduction in Phase 2 Trial

6 months ago

• Zerlasiran, a small interfering RNA (siRNA), significantly reduced lipoprotein(a) [Lp(a)] levels in a Phase 2 trial, showing over 80% reduction over 36 weeks. • The ALPACAR-360 trial demonstrated that successive doses of zerlasiran led to longer-lasting Lp(a) reduction, informing Phase 3 trial designs. • The study used a time-averaged Lp(a) reduction endpoint, reflecting treatment effect over time and dose intervals, a novel approach in nucleic acid therapy trials. • Injection-site reactions were the most common adverse effects, with no serious treatment-related events, supporting zerlasiran's safety profile.

Lp(a)-Lowering Therapies Show Promise in Phase II Trials

6 months ago

• Zerlasiran, a siRNA therapy, demonstrated an 85% reduction in Lp(a) levels over 36 weeks in the ALPACAR-360 trial, showing promise for ASCVD patients. • Muvalaplin, an oral agent, reduced Lp(a) by up to 85% in the KRAKEN trial, offering a potential alternative to injectable therapies for high Lp(a). • Both therapies were well-tolerated in phase II studies, with no significant safety concerns, marking a step forward in addressing unmet needs for Lp(a) lowering. • Clinical trials for both drugs are ongoing, with results expected in 2025 and 2026, which will determine whether lowering Lp(a) reduces cardiovascular events.

Oral Muvalaplin Shows Promise in Lowering Lipoprotein(a) Levels in Phase 2 Trial

6 months ago

• Muvalaplin, an oral drug by Eli Lilly, significantly reduced lipoprotein(a) (Lp(a)) levels in a Phase 2 trial, offering a potential non-injectable treatment option. • The trial demonstrated dose-dependent Lp(a) reduction, with up to 85.7% decrease at the 240 mg dose after 12 weeks, and was generally well-tolerated by participants. • Muvalaplin also reduced oxidized phospholipids, suggesting a mechanistic role in mitigating the relationship between Lp(a) and atherosclerotic disease. • The study highlights the need for increased Lp(a) testing coverage to identify and treat individuals at high cardiovascular risk.

RNAi Therapies Olpasiran and Zerlasiran Show Promise in Lowering Lipoprotein(a) in Cardiovascular Disease

6 months ago

• Olpasiran significantly reduces lipoprotein(a) (Lp(a)) levels by over 95% in patients with atherosclerotic cardiovascular disease, marking a potential breakthrough in managing this potent risk factor. • Zerlasiran, another siRNA therapeutic, demonstrates an average reduction of over 80% in Lp(a) levels over 36 weeks, with sustained effects observed at 60 weeks, offering a new approach to preventing premature heart disease. • Both therapies target Lp(a) production in the liver using RNA interference, showing minimal side effects and suggesting a promising strategy for managing elevated Lp(a) levels, which affect millions worldwide. • Further research is underway to assess the impact of these therapies on clinical outcomes and to address limitations such as the need for more diverse patient representation in trials.

Novartis and Apellis Advance C3G Therapies Towards FDA Submission

6 months ago

• Novartis' Fabhalta (iptacopan) demonstrated significant proteinuria reduction in the Phase III APPEAR-C3G trial, meeting its primary endpoint and supporting regulatory submissions. • Apellis' Empaveli (pegcetacoplan) showed a substantial reduction in proteinuria and C3c deposit clearance in the Phase III VALIANT trial, indicating early efficacy in C3G patients. • Nephrologists express a strong interest in new C3G therapies that can slow eGFR decline and reduce proteinuria, addressing the urgent need for innovative treatments. • Spherix data suggests treatment preferences may be influenced by administration route, with Fabhalta's oral administration potentially offering an advantage.

Drug Development Updates