Tirzepatide

MASH is a form of non-alcoholic liver disease. Credit: SEBASTIAN KAULITZKI / SCIENCE PHOTO LIBRARY via Getty Images. Eli Lilly is paying up to $630m for a Phase I metabolic-associated steatohepatitis (MASH) candidate from South Korea-based biotech OliX Pharmaceuticals, diversifying its pipeline for the disease with an RNA-based asset. Known as OLX75016, the candidate is an antisense RNAi oligonucleotide developed using OliX’s therapeutic RNAi platform. OliX focuses on developing therapies by inhibiting the expression of genes that cause disease through its technology. Lilly will make an initial payment to complete a Phase I trial that kicked off in Australia in February 2024. The study, set to enrol 58 healthy subjects, will evaluate the safety and tolerability of single and multiple ascending doses of OLX75016. While the ongoing Phase I trial is investigating OLX75016 for the treatment of MASH and liver fibrosis, the candidate is also in preclinical development for the treatment of obesity in combination with glucagon-like peptide-1 receptor agonist (GLP-1RA) semaglutide. The $630m agreement includes an upfront payment, as well as development and commercial milestones, according to a securities filing on Korea’s stock exchange. The deal establishes Lilly with a diverse pipeline to target the large market opportunity within MASH. The drugmaker’s blockbuster GLP-1RA drug tirzepatide – the active ingredient in Mounjaro and Zepbound – is being investigated as a treatment for MASH. In a Phase II trial (NCT04166773) readout in June 2024, Lilly reported that 51% to 54.9% of patients achieved an improvement in fibrosis without worsening of their disease at 52 weeks, compared to 21.3% to 25.2% on placebo. Lilly also invested in its nucleic acid infrastructure, unveiling a $700m R&D centre in Boston, US, in August 2024 – a facility focused on developing novel RNA-based and DNA-based medicine. MASH is a form of non-alcoholic liver disease, which describes a spectrum of conditions like steatosis, inflammation, and fibrosis marked by fat buildup in the liver. The disease, also associated with comorbidities such as obesity and diabetes, has been notoriously difficult to treat. The MASH treatment landscape has seen multiple trial failures and setbacks, with companies such as AstraZeneca terminating the development of its MASH therapies. In June 2023, the US Food and Drug Administration (FDA) rejected Intercept Pharmaceuticals’ new drug application (NDA) for its MASH therapy, obeticholic acid. The FDA cited concerns over the therapy’s safety profile, especially the potential risks of causing liver injury and diabetes. In March 2024, Madrigal Pharmaceuticals’ Rezdiffra (resmetirom), a type of thyroid hormone receptor beta (THR-beta) agonist, became the first and only approved therapy that does not require a liver biopsy for the treatment of patients with MASH and Stage 2–3 fibrosis.

In recent weeks, multinational pharmaceutical companies have released their 2024 earnings reports, revealing significant insights into their performance in the lucrative Chinese market. According to a review by Cybex, AstraZeneca emerged as the clear leader with $6.41 billion in revenue, reflecting an impressive 11% growth. This figure represents approximately 12% of AstraZeneca’s global market share. In contrast, Merck reported $5.39 billion in revenue for its China operations, a decline of nearly 20% from $6.71 billion in 2023. This drop makes Merck one of the only two companies to experience a downturn, with the largest decrease in revenue among its peers. Novartis secured the third spot with $3.9 billion in revenue, becoming the company with the highest growth rate among the seven multinational firms reviewed. Meanwhile, the weight-loss medication leaders, Novo Nordisk and Eli Lilly, also achieved double-digit growth in China, with revenues reaching $2.68 billion and $1.66 billion, respectively. AstraZeneca's growth can be attributed to its successful inclusion of nine drugs into China’s National Reimbursement Drug List in November 2023, along with the approval of eight new drugs and indications in 2024. Additionally, the company plans to increase capital expenditures by 50% to support production expansion and IT upgrades across various global sites, including China. Merck's performance was heavily impacted by a decline in demand for its HPV vaccine, GARDASIL, which saw a 41% drop in the fourth quarter of 2024 compared to the previous year. As a result, Merck will pause shipments of the HPV vaccine to China starting in February, likely to continue until mid-year. Novartis continues to thrive with its cholesterol-lowering drug Leqvio, which has shown a 114% increase in sales globally. The drug's performance in China has been vital, with a growing number of patients opting for self-pay despite it not being included in insurance plans. Novo Nordisk's performance in China was bolstered by its GLP-1 medications, contributing significantly to its growth with a 19% increase in sales. Eli Lilly also reported strong results, driven by the recent launch of its weight-loss drug Tirzepatide, which is expected to further enhance the company's growth trajectory in the Chinese market. As these major pharmaceutical companies adapt to the evolving landscape in China, the mixed results underscore the challenges and opportunities present in this critical market.