Zibotentan

Pictured: AstraZeneca building/iStock, Sundry Photography AstraZeneca announced in its recent quarterly update that it discontinued a Phase IIb trial for its investigational drug tozorakimab for the treatment of diabetic kidney disease due to efficacy. However, a new report from analytics firm GlobalData is bullish on the potential prospects of the pharma’s pipeline drug zibotentan, if it gets approval. Despite removing tozorakimab from its Phase II pipeline for diabetic kidney disease (DKD), zibotentan could be “an optimal treatment of choice” for patients and “of high value” for physicians trying to find treatments for the disease. “According to key opinion leaders (KOLs) interviewed by GlobalData, unmet needs in the kidney disease space include next-generation therapies with alternate mechanisms of action and enhanced clinical pro ” Kajal Jaddoo, senior pharma analyst at GlobalData, said in a statement. Tozorakimab, which acts by blocking endothelin receptors and binds to the ET-A receptor, made it to a Phase IIb DKD study in 2019, with GlobalData stating that there was evidence that increased inflammation is associated with deterioration in renal function. The trial’s hypothesis was that the drug may be “beneficial” for DKD patients on standard of care (SOC) who have inflammation as well. But that promise was not realized. “AstraZeneca has a strong commercial position and is well known in both the metabolic and cardiovascular markets. KOLs further emphasized that until further clinical data solidifies the superior or non-inferior safety and efficacy of monoclonal antibodies in combination with SOC, physicians will not substantially change their prescribing patterns,” Jaddoo said. Zibotentan acts by blocking growth receptors called endothelin receptors, binding selectively to the ET-A receptor and inhibiting endothelin-mediated mechanisms that promote cell proliferation, according to GlobalData. However, zibotentan has not seen success in other verticals, such as cancer. In 2010, zibotentan failed to improve survival in a late-phase trial in prostate cancer, while a year later a Phase III study in prostate cancer was stopped as it was unlikely to reach the endpoints of overall and progression-free survival. Still, in 2023, a combination of zibotentan and dapagliflozin showed statistically significant results in the urinary albumin-to-creatinine ratio (UACR) to asses albuminuria, with the UACR difference being down over 33% and earning a p-value of p<0.001. AstraZeneca saw a 90% plummet in its COVID-19 business in 2023 but still managed to secure 6% in total growth for the year and an 8% growth rate in the fourth quarter of last year. Areas such as cardiovascular, rare disease, oncology, and metabolism were significant growth factors for the pharma and executives are confident the company is poised for more growth in 2024. Tyler Patchen is a staff writer at BioSpace. You can reach him at tyler.patchen@biospace.com. Follow him on LinkedIn.

Over the past few days, Big Pharma and biotech companies alike presented results at the American Society of Nephrology’s annual kidney week. Endpoints News sifted through the data to highlight several key readouts, including those that triggered notable stock reactions or pushed forward a new mechanism. On Friday, AstraZeneca unveiled positive data from the Phase IIb ZENITH-CKD study of its investigational ETA receptor antagonist, zibotentan, in combination with SGLT2 inhibitor Farxiga in chronic kidney disease. The pharma major plans to advance the combination to a Phase III trial with 1,500 people, set to start in the first quarter of 2024. You’ll get access to free articles each month, plus you can customize what newsletters get delivered to your inbox each week, including breaking news.