AstraZeneca Pursues Distinctive Approach in Kidney Disease Therapy Post-Trial Halt

AstraZeneca recently reported the discontinuation of a Phase IIb clinical trial for its drug candidate tozorakimab, intended for diabetic kidney disease (DKD), due to unsatisfactory efficacy. This decision followed the drug's progression to a Phase IIb study in 2019, which was based on the understanding that increased inflammation is linked to a decline in kidney function. The trial aimed to determine if tozorakimab could provide benefits to DKD patients receiving standard care who also exhibit inflammation.

However, a contrasting view is presented by analytics firm GlobalData, which holds a positive outlook for AstraZeneca's zibotentan, should it receive regulatory approval. According to GlobalData's senior pharmaceutical analyst, Kajal Jaddoo, there is a significant demand for next-generation therapies with different mechanisms of action and improved clinical profiles in the treatment of kidney disease.

Zibotentan operates by targeting endothelin receptors, which are growth receptors, selectively binding to the ET-A receptor and hindering endothelin-induced processes that lead to cell proliferation. Despite zibotentan's setbacks in other areas, such as its unsuccessful attempt to improve survival rates in a late-phase prostate cancer trial in 2010 and the discontinuation of a Phase III study for the same indication in 2011 due to the unlikelihood of meeting its primary endpoints, it has shown promise in the DKD field.

In 2023, a study combining zibotentan with dapagliflozin demonstrated significant improvements in the urinary albumin-to-creatinine ratio (UACR), a measure used to assess albuminuria. The UACR difference was reduced by over 33%, with a statistically significant p-value of less than 0.001.

AstraZeneca has experienced a significant decline in its COVID-19 business in 2023, with a 90% drop. Nonetheless, the company managed to achieve a 6% overall growth for the year and an 8% growth rate in the fourth quarter. Growth drivers for the pharmaceutical company include cardiovascular, rare disease, oncology, and metabolism sectors. The company's executives are optimistic about continued growth in 2024.

It is important to note that AstraZeneca's strong market presence in metabolic and cardiovascular markets, as highlighted by key opinion leaders, suggests that without further clinical evidence supporting the superior safety and efficacy of monoclonal antibodies in combination with standard care, prescribing habits among physicians are unlikely to change significantly.