Enpatoran

Plus, news about Tris Pharma and ARS Pharmaceuticals: Merck KGaA’s lupus drug yields mixed data in mid-stage trial: The drugmaker’s TLR7/8 inhibitor, called enpatoran, missed one of two Phase 2 primary endpoints in a cohort of patients with systemic lupus erythematosus, according to chief financial officer Helene von Roeder on the company’s earnings call on Thursday. The drug previously showed promise patients with cutaneous lupus in the same trial, and Merck said the overall data support further development. — Ayisha Sharma Zymeworks deprioritizes ADC: The company is pausing Phase 1 development of ZW220, which is designed to target sodium-dependent phosphate transporter 2b. It had been considering testing the ADC in ovarian and non-small cell lung cancer. Zymeworks noted that the program still has “strong commercial rationale with partnership potential.” — Max Gelman Tris Pharma reports another Phase 3 success for pain drug: The treatment, called cebranopadol, succeeded in a trial measuring its pain reduction abilities after surgical bunion removal. The win comes less than two months after a Phase 3 study in patients who had undergone tummy tucks also met its primary endpoint. The drug is designed to target the pathway used by painkillers like Vicodin and morphine to create their sedative and analgesic effects as well as another receptor that has a “modulatory role” on that pathway (though it still belongs to the broader family of opioid receptors). — Max Gelman ARS Pharmaceuticals’ neffy gets another approval: The company said Wednesday that the FDA approved neffy 1 mg to treat Type I allergic reactions in children who are at least 4 years old and hit a weight requirement. The nasal spray was first approved in the US last summer. — Jaimy Lee Editor’s note: This article and its headline were corrected to note that Merck KGaA’s lupus trial had mixed data and to correct a quote attribution. A previous version of the article incorrectly stated that the trial had failed.

Merck KGaA on Thursday reported its annual results for 2024, although investors eager for an update on a potential deal with SpringWorks Therapeutics were left frustrated. The German drugmaker simply reaffirmed that it is in advanced discussions about a possible acquisition of SpringWorks, although there is no certainty that an agreement will be signed. Rumours of a transaction between the parties first surfaced on February 10, with Merck confirming later the same day that talks were ongoing. A purchase of SpringWorks would give Merck the oral gamma secretase inhibitor Ogsiveo (nirogacestat), which is approved for desmoid tumours, as well as the MEK inhibitor mirdametinib, currently under review by the FDA for neurofibromatosis type 1-associated plexiform neurofibromas.The acquisition of SpringWorks would revitalise Merck's pipeline, following a number of recent setbacks, including the failure of a pair of Phase III studies for its lead oncology candidate xevinapant. While the company's healthcare segment posted 5% growth last year to €8.5 billion ($9.2 billion), driven by oncology — which was up 10.5% to €2 billion — it is heavily reliant on its 20-year-old drug Erbitux.Erbitux biosimilars on the horizonThe anti-EGFR monoclonal antibody generated sales in 2024 of €1.2 billion, up 13.3% over the prior year. Merck noted that growth for Erbitux was led by Latin America, particularly Mexico, as well as Europe and China, tempered by negative pricing effects in Japan.Asked on an analyst call about the growth potential of Erbitux, particularly in China, Peter Guenter — CEO of Merck's healthcare unit — noted that sales of the product are forecast to increase this year, with biosimilars not expected to launch before 2026. Guenter indicated that China, which accounts for about 25% of Erbitux revenue, is "an important growth driver, but actually the brand is very dynamic across the world."While Erbitux faces competition in China from Simcere Pharmaceutical's Enlituo, Guenter clarified that the product — approved last June — is not classified as a biosimilar, but rather a non-comparable biologic. "And that has, of course, relatively important implications in terms of, you know, lack of substitution," Guenter explained, as well as inclusion on the reimbursement drug list and volume-based procurement programme.Merck's other key drug, the multiple sclerosis (MS) therapy Mavenclad, achieved blockbuster status in 2024 for the first time, posting an 11.1% increase in revenue to €1.1 billion. Meanwhile, its older MS treatment Rebif declined 11.6% to €626 million in line with the wider interferon market.For the current year, the firm expects sales in its healthcare unit to be between €8.3 billion and €8.9 billion, representing organic growth of up to 5%.Pipeline questions continueMerck also disclosed Thursday that the oral TLR7/8 inhibitor enpatoran failed to meet the primary endpoint of the systemic lupus erythematosus cohort of the mid-stage WILLOW study. Despite what Guenter called "a near miss" in the trial, the company plans further development of the drug, given "promising responses" in patient subgroups and the totality of data, including positive results from the cutaneous lupus erythematosus arm of WILLOW.Guenter explained "the good news is that we see clear responses in predefined subpopulations. So we can really say that the drug clearly hits the target." These subgroups include patients with skin manifestations within the lupus cluster, those with a strong interferon gene signature and also those with high steroid use at baseline.Meanwhile, chief financial officer Helene von Roeder noted that Inspirna "informed [us] about negative top-line data" from an ongoing Phase II trial of ompenaclid in RAS-mutated advanced or metastatic colorectal cancer. The SLC6A8 inhibitor — also known as RGX-202 — was the focus of a licensing agreement between the parties last year. However, von Roeder indicated that the mid-stage failure means "we will not exercise the US option" on the drug, but will instead record an impairment charge of around €15 million in the current quarter.