PLPP

AstraZeneca is migrating into the final phases of a possible Covid-19 vaccine. Credit: Shutterstock AstraZeneca has discontinued a Phase III trial of Truqap (capivasertib) after a review concluded that the study was unlikely to meet its endpoints. The CAPItello-280 study (NCT05348577) was investigating Truqap in combination with docetaxel and androgen-deprivation therapy (ADT) compared to docetaxel and ADT with placebo in patients with metastatic castration-resistant prostate cancer (mCRPC). The pharma giant decided to scrap the study after an Independent Data Monitoring Committee (IDMC) said it was unlikely that the combination would meet the dual primary endpoints of radiographic progression-free survival (rPFS) and overall survival (OS) versus the comparator arm. AstraZeneca said the safety and tolerability profile for Truqap was consistent with other trials. This is another blow for one of AstraZeneca’s flagship oncology products, which failed to meet the primary endpoint of overall survival (OS) in either patient group in the Phase III CAPItello-290 trial (NCT03997123) in June 2024. The CAPItello-290 study was investigating the drug in combination with paclitaxel in patients with locally advanced (inoperable) or metastatic triple-negative breast cancer (TNBC). In November 2024, however , the drug did prove efficacious in the Phase III CAPItello-281 trial, meeting the primary endpoint of radiographic progression-free survival in patients with PTEN-deficient de novo metastatic hormone-sensitive prostate cancer. GlobalData Strategic Intelligence US Tariffs are shifting - will you react or anticipate? Don’t let policy changes catch you off guard. Stay proactive with real-time data and expert analysis. By GlobalData Learn more about Strategic Intelligence Truqap is an adenosine triphosphate (ATP)-competitive inhibitor that targets all three AKT isoforms (AKT1/2/3). It was approved by the US Food and Drug Administration (FDA) in November 2023 for use in combination with Faslodex for the treatment of advanced HR-positive breast cancer. The drug was given priority review and assessed through Project Orbis, a programme that facilitates the simultaneous submission and evaluation of oncology medications by collaborating with international partners. The drug has since been approved for use in Europe and the UK, with access available through the NHS. GlobalData forecasts that Truqap will reach blockbuster status in 2027, with global sales in 2030 set to hit $1.78bn. GlobalData is the parent company of Clinical Trials Arena .

iStock, Andrii Yalanskyi The drug, a small molecule protein inhibitor, brought in $132 million in the first quarter, missing consensus estimates by 17%. AstraZeneca is discontinuing the late-stage CAPItello-280 trial, which was evaluating its AKT blocker Truqap in patients with metastatic castration-resistant prostate cancer, the pharma announced on Tuesday. The study, which combined Truqap with docetaxel and androgen-deprivation therapy (ADT), is unlikely to meet its dual primary endpoints of overall survival and radiographic progression-free survival (rPFS), as per an interim analysis by an independent data monitoring committee. AstraZeneca did not provide specific data in its news release on Tuesday, revealing only that it will work with investigators to make sure that patients undergo “necessary follow-up.” Despite this failure, the pharma remains confident in Truqap’s market opportunity, with CEO Pascal Soirot telling reporters in a media call Tuesday that AstraZeneca still expects the drug to bring in between $1 billion and $3 billion per year, according to Fierce Pharma . In the first quarter, Truqap brought in $132 million in sales, driven by its dominant market presence in the second-line setting for patients with breast cancer who have altered biomarkers, according to the pharma’s Q1 earnings report . This fell 17% below consensus estimates, however, as per a Leerink analyst note on Tuesday. “Impressively, at one year post-launch, Truqap has achieved nearly 100% market share in the AKT/PTEN biomarker-altered population, with additional opportunity for growth in the PIK3CA population,” Dave Fredrickson, executive vice president of AstraZeneca’s Oncology Business, said during the company’s investor call. Designed to be taken orally, Truqap is a small-molecule inhibitor of all three isoforms of the AKT protein, which in cancers is often mutated and activated, leading to the abnormal cell growth and survival that are hallmarks of malignancies. Truqap’s mechanism of action allows it to disrupt this pathway and block tumor growth. So far, Truqap has one approval under its belt, granted in November 2023 when the FDA cleared it for use in patients with HR-positive, HER2-negative locally advanced or metastatic breast cancer, whose tumors harbor mutations to the PIK3CA/AKT1/PTEN pathway. AstraZeneca has since been trying to push Truqap into new indications, though its results have been mixed so far. In November last year, the pharma announced that the drug hit its key outcomes in the Phase III CAPItello-281 study, significantly improving rPFS when used with ADT and abiraterone in a specific subset of patients with prostate cancer—those who had PTEN-deficient  de novo   metastatic hormone-sensitive disease. However, a few months earlier, in June 2024, Truqap failed the late-stage CAPItello-290 trial in metastatic triple-negative breast cancer. The drug could not significantly improve overall survival in patients with this condition.

AstraZeneca's first-in-class AKT inhibitor Truqap has flopped in a phase 3 trial for the second time. AstraZeneca has come up short in another phase 3 trial of the AKT inhibitor Truqap, raising more questions about the blockbuster potential of the first-in-class cancer treatment.Alongside its first-quarter earnings report, AZ revealed that an interim analysis of a study investigating Truqap in metastatic castration-resistant prostate cancer showed it was unlikely to meet the dual primary endpoints of progression-free survival and overall survival.The CAPItello-280 trial was evaluating Truqap added to androgen-deprivation therapy (ADT) and the chemotherapy docetaxel, comparing the combination’s performance to ADT plus docetaxel. It is the second phase 3 trial flop for highly touted Truqap, which was approved in November of 2023 in a narrow group of HR-positive, HER2-negative breast cancers with certain genetic alterations. In the CAPItello-290 study, which evaluated Truqap in triple-negative breast cancer, it failed to move the needle when added to the chemotherapy paclitaxel.In a conference call Tuesday with reporters, AZ CEO Pascal Soriot reiterated the company’s projection that Truqap can achieve between $1 billion and $3 billion in annual sales. “We still believe that we can be in that range,” Soriot said. “Of course, having missed on this prostate study, the potential will be smaller.”The CAPItello-280 setting was a bit risky, he added. Meanwhile, the phase 3 CAPItello-281 trial evaluating Truqap in de novo PTEN-deficient metastatic hormone-sensitive prostate cancer remains ongoing to assess overall survival data after the primary endpoint of progression-free survival was met last year.AZ’s first disappointment with Truqap came with its FDA nod, which was for a smaller patient population than the company had hoped because of a biomarker stipulation.Truqap was off to a decent start, reaching $430 million in 2024 sales in its first full year on the market. However, its $132 million haul in the first quarter of this year was down sequentially from $163 million and came 17% below analysts’ expectations.  Elsewhere, with the looming Trump administration tariffs on pharmaceuticals, AZ said that it has begun to move production of some drugs from Europe to the U.S. Chief financial officer Aradhana Sarin added that AZ has a built-in “dual-source supply” capability and can increase capacity of its U.S.-based facilities when needed.“The incremental investment for that to happen will be manageable,” Sarin said. AZ reported a 7% year-over-year revenue increase in the first quarter to $13.6 billion and reiterated its guidance to achieve a high single-digit increase in sales in 2025, coming off a year in which its revenue increased by 18%.