Cobolimab

GSK may not have been surprised its anti-TIM-3 drug couldn’t secure a phase 3 win based on how its pharma peers have struggled.\n GSK’s cobolimab has become the latest anti-TIM-3 antibody to flunk a crucial oncology test, as the pharma absorbs a more than $600 million hit from its anti-TIGIT drug failure.The British Big Pharma had been evaluating cobolimab—which it acquired in the $5.1 billion Tesaro takeover in 2018—in various combinations with oncology med Jemperli and the chemotherapy docetaxel in a phase 3 study of 750 patients with non-small cell lung cancer (NSCLC).The company revealed in its second-quarter earnings this morning that the study didn’t reach its primary endpoint of improving overall survival in advanced NSCLC after prior immuno-oncology therapies.“All regimens were well-tolerated and toxicities were consistent with known safety profiles of docetaxel and immune checkpoint inhibitors,” GSK said in its July 30 earnings release (PDF). “This remains a challenging treatment setting where novel combinations have yet to improve outcomes for most patients.”The late-stage fail doesn\'t mark the end of GSK\'s hopes for cobolimab. The company is still evaluating the drug in a phase 1/2 trial in a range of pediatric cancer settings as well as in a midstage trial for advanced liver cancer.TIM-3 is expressed by immune effector cells, where it acts as an immune checkpoint, and leukemic stem cells, leading various Big Pharmas to identify the receptor as a way to simultaneously activate the immune system and suppress the proliferation of cancer cells.GSK may not have been surprised that cobolimab couldn’t secure a phase 3 win. The drug was the most advanced anti-TIM-3 antibody left standing after Novartis’ own candidate failed a late-stage study in patients with myelodysplastic syndrome or leukemia at the start of 2024.While Novartis focused on blood cancers, GSK and other big names with TIM-3 candidates had largely looked at solid tumors. Roche removed (PDF) a PD-1xTIM-3 bispecific from its pipeline in 2022, while Bristol Myers Squibb terminated a phase 1 trial of a TIM-3 candidate, BMS-986299, in 2022 because its “business objectives” had changed. Eli Lilly and Incyte have also axed their respective TIM-3 drugs. AstraZeneca appears to still have a foot in the anti-TIM-3 space, with a PD-1xTIM-3 bispecific that is due to complete a phase 1/2 study this year.TIM-3 wasn’t the only high-risk cancer target where GSK crashed and burned this quarter. The pharma revealed in the same earnings document that its decision to end development of the anti-TIGIT antibody belrestotug had resulted in a 471 million pound sterling ($629 million) impairment charge.GSK paid iTeos $625 million upfront for the rights to belrestotug four years ago. In the wake of belrestotug’s phase 2 failure, the biotech initially planned to wind down operations before accepting a buyout offer from Concentra Biosciences earlier this month.This morning’s release also revealed that GSK has discontinued a phase 2-stage adjuvanted recombinant protein vaccine for malaria dubbed GSK3437949. A spokesperson for the company put this move in the context of the pharma’s recently announced push into second-generation, multistage malaria vaccines.Meanwhile, sanfetrinem cilexetil—an oral prodrug of the antibiotic sanfetrinem—has been removed from the company’s phase 2 pipeline after having “not compared favourably in early studies to existing treatments and other tuberculosis-specific assets also in development at GSK,” the spokesperson said.

GSK CEO Emma Walmsley said the company is steadfast in bringing Blenrep back to the US market after several FDA setbacks. In its second-quarter earnings report Wednesday, the company also revealed a Phase 3 trial of various combinations featuring its anti-TIM-3 antibody, called cobolimab, had failed. Walmsley said in a media call GSK is “very confident in the Blenrep data, and really pleased that we have an updated PDUFA date.” She added that “we are in constructive dialogue with the agency: answering questions, providing some additional data.” GSK has previously said Blenrep could reach £3 billion ($4 billion) a year in global sales in second-line multiple myeloma. Last week, the FDA extended its review of Blenrep by around three months after an advisory committee largely voted against the risk-benefit profiles of two separate combinations including the drug for second-line disease. The agency now has until Oct. 23 to make a decision. During the meeting, committee members raised their concerns over the fact that just 5% of patients included in Blenrep’s clinical development were from the US, as well as the limited enrollment of African American patients. “The representation of our studies was consistent with other studies for approved multiple myeloma indications in the US designed as global registrational studies,” Walmsley said on the call. “We did have a significant profile of European countries, but all of the demographics and outcomes in those countries are also consistent with the US.” This is GSK’s second attempt to get Blenrep past the finish line. The medicine was originally greenlit in 2020 under an accelerated approval pathway, but the company voluntarily pulled it from the US market in 2022 after it flunked a confirmatory trial. The drug was approved in Europe last week. Elsewhere in its oncology pipeline, the UK drugmaker’s Phase 3 trial of its anti-TIM-3 antibody cobolimab in doublet or triplet combinations with Jemperli and docetaxel in non-small cell lung cancer ended in failure last month. The study missed its primary endpoint of improving overall survival in pretreated patients. GSK also removed two programs from Phase 2 development: A recombinant protein codenamed GSK3437949 for malaria, and a serine beta-lactamase inhibitor called sanfetrinem cilexetil for tuberculosis. The malaria drop comes as the company is shifting its focus to second-generation vaccines for the disease, a spokesperson told Endpoints News in an email. The tuberculosis asset “has not compared favourably in early studies to existing treatments,” they said. Elsewhere, Walmsley said that GSK is in dialogue with the Trump administration on how to “keep the US leading the world in terms of being a market for innovation, and to make sure that we are passing on the discounts that we provide to patients.” She declined to provide further details of the talks, but noted the company “would like to see all countries investing more and recognizing the value more that [healthcare] innovation brings.” Walmsley is the latest big pharma CEO, along with AstraZeneca’s Pascal Soriot and Roche’s Thomas Schinecker , to mention discussions with the Trump administration on US drug prices. The UK pharma’s Q2 sales came in 2% ahead of Wall Street consensus estimates at £8 billion ($10.7 billion). The success was largely driven by GSK’s vaccines franchise, which saw sales increase 9% from the same period last year to £2.1 billion ($2.8 billion). In particular, the £853 million in sales for shingles vaccine Shingrix were buoyed by launch uptake in France and continued demand in other European markets and Japan. GSK’s share price is up 1.5% on the London Stock Exchange.