Depemokimab

Upstream Bio unveiled what it described as "positive" Phase II results for verekitug in severe asthma, a treatment that could go head-to-head with Amgen and AstraZeneca's TSLP inhibitor Tezspire (tezepelumab). But investors weren't impressed.After initially surging nearly 30% in premarket trade Wednesday, Upstream's shares did an about-face, falling about 50% mid-morning as analysts weighed in on the data, with concerns about how often patients would need to take the drug."Investor feedback had been focused on achieving success of the [every-24-week] dosing arm and key secondary [goals] across both arms," William Blair analyst Matt Phipps said in a note. "Shares could see some volatility today as investors analyse the totality of the data to determine the competitive position of verekitug against other long-acting TSLP programmes."Upstream's mAb is designed to block the receptor for TSLP, a cytokine target upstream in the inflammatory cascade that drives multiple downstream immune pathways.The Phase II VALIANT study enrolled 478 adults with severe asthma and tested three verekitug dosing regimens administered subcutaneously against placebo over a period of up to 60 weeks.Quarterly outperforms half-year dosingUpstream said the trial met its primary endpoint, showing statistically significant reductions in annualised asthma exacerbation rate (AER). Patients receiving 100 mg every 12 weeks experienced a 56% reduction in exacerbations compared to placebo, while those receiving 400 mg every 24 weeks saw a 39% reduction. A lower 100-mg dose given every 24 weeks achieved statistical significance for exacerbations, but did not consistently improve other clinical measures.The AER reductions seen with quarterly dosing appear broadly comparable with Tezspire, which was approved for severe asthma in 2021 and is given every four weeks. In the Phase III NAVIGATOR trial, Tezspire reduced annual exacerbations by 56%, while earlier Phase II PATHWAY data had shown up to a 71% reduction.Prior to Wednesday's VALIANT readout, Mizuho analysts citing two key opinion leaders (KOLs) said "+/- 10% on relative AER reduction vs. tezepelumab [would be considered] a positive outcome." However, while acknowledging the theoretical benefit of less dosing, the KOLs also suggested the quarterly regimen would have "more real-world value" than every-24-week dosing since it still has the benefit of convenience, "with minimal risk to patient loss — easier to maintain continuity with this dosing interval."Treatment landscapeMeanwhile, a KOL interviewed for a recent FirstWord report noted that if verekitug "could be given every six months, that seems to be a big advantage." KOLs in the report also suggested that long-acting anti-TSLP mAbs such as verekitug and GSK's AIO-001 — assuming comparable efficacy to Tezspire — could not only eat into Tezspire's market, but also that of short-acting anti–IL-5 therapies and Dupixent (dupilumab), which is marketed by Sanofi and Regeneron (see – KOL Insight – Asthma).In December, the FDA cleared GSK's long-acting IL-5 inhibitor Exdensur (depemokimab), which made it the first biologic with twice-yearly dosing approved for severe asthma in the US (see – Physician Views Results: Twice-yearly dosing for GSK's Exdensur resonates with pulmonologists, but efficacy parity, secondary endpoints and cost will shape uptake and Spotlight On: Why pulmonologists are taking a wait-and-see approach with Exdensur).Gearing up for Phase IIIUpstream also reported secondary endpoints from the VALIANT trial. Placebo-adjusted improvements in lung function, measured by forced expiratory volume in one second (FEV1), reached 122 mL at week 60 in the quarterly dosing group and 139 mL in the every-six-months cohort. Verekitug also suppressed exhaled nitric oxide (FeNO), a biomarker of airway inflammation, with reductions from baseline of 43.5% and 44.9, respectively.The therapy was generally well tolerated across doses and showed a safety profile consistent with earlier studies, while more than 90% of eligible patients elected to enrol in the long-term VALOUR extension trial."Together with the positive results from our VIBRANT trial in CRSwNP [chronic rhinosinusitis with nasal polyps], we now have an opportunity to incorporate both strong clinical data sets with an in-depth analysis of the aggregate pharmacology findings to guide data-driven decisions about dose selection and trial design" for Phase III studies in both severe asthma and CRSwNP, said Aaron Deykin, chief medical officer and R&D head at Upstream.

Luke Miels inherited the GSK CEO role as the company posted what he called strong performance last year. In his first investor update as GSK’s CEO, Luke Miels defined a core of his vision for the company’s next chapter: “We need to be more product-centric as a company.”Being product-centric means everyone at GSK, from R&D and manufacturing to commercialization and administrative functions, should be clear about how their role drives the company’s goal of making drugs that improve clinical outcomes for patients, Miels said during a press call Wednesday.“When you look at the level of communication, discussions, focus time that a company spends, I want to really see that to be massively dominated by products,” he said.In addition to product-centricity, Miels also wants GSK to have more “scientific courage” to accelerate its pipeline and be “more agile to capitalize on opportunities.” Miels succeeded Emma Walmsley to become GSK’s new CEO at the beginning of 2026, inheriting the role as GSK posted what he called strong performance last year. Full-year revenue grew 7% at constant exchange rates to 32.7 billion pounds sterling ($44.9 billion), and a fourth-quarter haul of 8.6 billion pounds came 2% ahead of analysts’ consensus.Even though GSK expects milder sales growth—between 3% and 5%—this year, Miels stood by the company’s ambitious target of generating more than 40 billion pounds by 2031, which was set when he was chief commercial officer.  GSK will test its new CEO’s product-centric approach this year with two key launches: long-acting respiratory disease biologic Exdensur and multiple myeloma antibody-drug conjugate Blenrep, both approved by the FDA in the fourth quarter of 2025.With Exdensur, GSK has transferred its Nucala sales force to detail the new half-yearly regimen, leaving Nucala’s chronic obstructive pulmonary disease (COPD) launch to the Trelegy team, Miels said on an investor call Wednesday.“We need to place our bets on the future, and the ultimate future with IL-5 and higher [eosinophils] is gonna be long-acting Exdensur for COPD,” he said.Exdensur’s current FDA approval covers its use as an add-on therapy for severe eosinophilic asthma. In COPD, GSK has two phase 3 trials, Endura-1 and -2, for testing the anti-IL-5 antibody as an add-on therapy to treat moderate to severe COPD with type 2 inflammation. In the fourth quarter, GSK launched a third phase 3 trial, dubbed Vigilant, to assess early use of Exdensur in COPD patients who have had one exacerbation and are at a high risk for future exacerbations.Despite the many biologics available for respiratory diseases, GSK still sees “a significant opportunity in the bio-naïve population, as only 27% of U.S. eligible patients are on a biologic, and market research shows that 97% of patients would prefer or like to switch to a biologic with six-monthly dosing,” Nina Mojas, GSK’s president of global product strategy, said on the investor call.As for Blenrep, the BCMA agent remains a show-me story after making a comeback from a previous market withdrawal. Despite lofty peak sales figures, Mojas acknowledged that the product’s launch will be a slow ramp as GSK supports prescribers and patients to ensure a positive first experience.Despite its being an off-the-shelf option compared with BCMA CAR-T therapies, Blenrep comes with notable eye toxicity and is therefore only available through an FDA-mandated REMS safety program. To mitigate that side effect, GSK has educated about 18,000 eye care professionals in the U.S., enabling their collaboration with oncologists, Mojas said. GSK launched Blenrep in the U.K. before securing an FDA go-ahead in late October, and the company expects to see similar interest in the drug albeit slow uptake because of the need for coordination with eye care professionals.Still, Miels highlighted a roughly 50-50 split between academic and community practices during early adoption of Blenrep.“Our strategy is to focus on the community,” he said. “With a product that is being relaunched and not a lot of experience in the community, I think this is an encouraging trajectory.” Meanwhile, the vaccines business at GSK is undergoing significant uncertainty due to disruptive U.S. policy changes.In the fourth quarter, GSK’s sales from vaccines grew 4% year over year to 2.3 billion pounds, bringing the full-year total to nearly 9.2 billion pounds ($12.6 billion).The company’s flagship shingles vaccine Shingrix delivered a 20% sales increase during the fourth quarter thanks to Europe and international markets, while the U.S. logged a 17% decrease as the remaining unvaccinated market proves difficult to penetrate.The U.S. Department of Health and Human Services, under the leadership of Secretary Robert F. Kennedy Jr., has challenged many longtime vaccine practices, including recently walking back recommendations for six immunizations for children. The moves have dealt a number on overall vaccines sales at several companies, although GSK expects the impact to be “manageable.”“We continue to monitor the evolving pediatric vaccine landscape in the U.S.,” Mojas said. “At this time, insurance coverage remains as before, and we expect the recent HHS changes to be manageable.”For 2026, GSK expects sales from vaccines to decline in the low-single-digit percentage or remain stable.