Lepodisiran sodium

iStock, Alona Horkova The ADARx Pharmaceuticals partnership, which could be worth “several billion dollars” in the end, adds to AbbVie’s existing work in the space after the $1.4 billion acquisition of Aliada Therapeutics in October 2024. AbbVie dipped its toes into the world of small interfering RNA last year with the buyout of Aliada Therapeutics. Now, the Illinois pharma is diving in further with a $335 million upfront payment to work with ADARx Pharmaceuticals to find new treatments. The deal spans disease areas but neuroscience, immunology and oncology were noted in the Wednesday release as focus areas. ADARx will receive the upfront fee and also be eligible for “several billion dollars” in milestones down the line, the companies said. ADARx will use its siRNA technology to find new molecules, with AbbVie contributing expertise in antibody engineering, antibody drug conjugates and tissue delivery. siRNA medicines regulate gene expression and protein production and can prevent the production of disease-causing proteins by targeting messenger RNA (mRNA) that encodes for these proteins. The ADARx partnership adds to AbbVie’s existing work in the space after its $1.4 billion acquisition of Aliada Therapeutics in October 2024. That deal was focused on central nervous system disorders, particularly the anti-pyroglutamate amyloid beta (3pE-Aβ) antibody ALIA-1758 for Alzheimer’s disease. Beyond the AbbVie partnership, ADARx has a pipeline of clinical-stage medicines for complement-mediated, cardiovascular and thrombotic diseases. The most advanced is ADX-324, which is nearing Phase III testing for hereditary angioedema. The biotech also has programs in discovery for obesity and neurodegeneration. ADARx last raised funds in August 2023, taking home $200 million in series C funds to advance ADX-324 as well as ADX-038, which is in development for multiple complement-mediated diseases. siRNA has become a hot space for pharma . Also on Wednesday, GSK inked a deal to buy Boston Pharmaceuticals’ efimosfermin alfa. The plan is to combine the FGF21 analog with GSK’s siRNA therapy GSK’990. The new deals follow Eli Lilly’s March announcement that its siRNA therapy lepodisiran reduced lipoprotein(a) levels by nearly 94% in patients at risk of cardiovascular events such as heart attack or stroke. And Boehringer Ingelheim signed a deal in January 2024 worth up to $2 billion with Chinese biotech Suzhou Ribo Life Science and its Swedish unit Ribocure Pharmaceuticals to develop siRNA-based treatments for metabolic dysfunction-associated steatohepatitis.

Recent data revealed at an important medical conference highlights that Eli Lilly's lipid-lowering drug, Lepodisiran, significantly reduces levels of lipoprotein(a) (Lp(a)), a key risk factor for genetic heart disease. Published in the New England Journal of Medicine, the mid-stage trial demonstrated a remarkable 93.9% average reduction in Lp(a) levels within six months after a single 400 mg dose, compared to the placebo group. The trial involved 72 patients in the treatment group and 69 in the placebo group, with a subsequent injection after six months leading to an almost 95% reduction in Lp(a) levels over a year. Notably, no serious adverse events related to the drug were reported. Unlike LDL cholesterol, which can be managed through diet and statins, there are currently no approved therapies targeting Lp(a). Elevated Lp(a) levels significantly increase the risk of heart attacks, strokes, aortic valve stenosis, and peripheral artery disease. Approximately 20% of the global population, or about 1.4 billion people, have elevated Lp(a), with the highest risk observed in the African population. Patients typically rely on statins for controlling other lipid markers, but these do not affect Lp(a). In the competitive landscape of Lp(a) therapies, Eli Lilly, Novartis, and Amgen are making strides, with Merck also entering the field through licensing agreements. Lepodisiran is administered once a month, while Pelacarsen (by Novartis) has shown an 80% average reduction in Lp(a) levels with an 80 mg/month subcutaneous injection. However, the Phase III clinical data for Pelacarsen has been postponed to mid-2026, raising concerns about its market performance. Amgen's siRNA therapy, Olpasiran, appears to be a strong competitor, showing over 95% reduction in Lp(a) levels in patients with atherosclerotic cardiovascular disease after every 12 weeks of administration. Results are also expected in 2026. Novartis's Pelacarsen, an antisense oligonucleotide (ASO), selectively cleaves the mRNA of the LPA gene, effectively reducing Lp(a) synthesis. In its Phase II trial, Pelacarsen significantly lowered Lp(a) levels, with 98% of patients achieving levels below 50 mg/dL. However, it requires more frequent dosing compared to Lepodisiran. In addition to Lepodisiran, Eli Lilly is concurrently developing an oral small molecule Lp(a) inhibitor, Muvalaplin, creating a dual strategy of injectable and oral therapies to cater to diverse patient needs. Furthermore, on March 25, Merck announced a collaboration with Hengrui Medicine to develop an oral Lp(a) drug, HRS-5346, which could emerge as another potential player in the market. The success of this collaboration hinges on regulatory approvals and meeting standard transaction conditions, with completion expected in Q2 2025. Overall, the development of Lepodisiran exemplifies the ongoing exploration of cardiovascular targets following the success of PCSK9 inhibitors. Its Phase III trial outcomes could significantly influence the future landscape of lipid-lowering therapies, potentially paving the way for combined PCSK9 and Lp(a) treatment strategies.