Novo Nordisk’s CLARION-CKD Trial Shut Down After Unsuccessful Results Causing Impairment Loss

Novo Nordisk A/S will recognize a dramatic decrease in asset value of approximately US$ 8.2 million due to unsuccessful outcomes from their CLARION-CKD phase 3 trial. The trial featured the evaluation of their ocedurenone drug, in which the primary end goal was to assess the efficacy and safety of bardoxolone methyl in delaying the advancement of chronic kidney disease (CKD) to end-stage kidney disease (ESKD). Due to failed results, Novo officially announced their decision to terminate CLARION-CKD phase 3 trial after their expectations were not met.

Ocedurenone a US$1.3 Billion Miss for Novo in Diabetes and CKD Therapeutic Advances

Ocedurenone, known as KBP-5074, is a non-steroidal, selective mineralocorticoid receptor antagonist (nsMRA) used to treat uncontrolled hypertension and advanced chronic kidney disease. It is characterized by its long half-life and high receptor affinity. Novo Nordisk formally acquired ocedurenone from KBP Biosciences PTE., Ltd. in late 2023 for up to $1.3 billion. KBP Biosciences specializes in the discovery, development, and commercialization of small molecule therapeutics. This sale reflected the company’s strategy to maximize ocedurenone’s therapeutic potential through Novo Nordisk’s global distribution network and strong marketing capabilities.

Executive Vice President and Head of Development at Novo Nordisk, Martin Holst Lange expressed in a press release prior to Novo Nordisk’s ocedurenone acquisition, “With its expected benefit-risk profile, ocedurenone has best-in-class potential in treating uncontrolled hypertension and could help address a major unmet medical need in people living with cardiovascular disease and chronic kidney disease.” This statement aligned with the company’s strategy on the expansion of the company’s treatment focus, rather than just developing programs focused on diabetes. Camilla Sylvest, executive vice president, Commercial Strategy & Corporate Affairs at Novo Nordisk added, “This deal is closely aligned with our strategic focus on expanding from our core in diabetes into other serious chronic diseases.”

Evaluation of CLARION-CKD Phase 3 Trial and its Findings in Treating CKD

The CLARION-CKD trial was a placebo-controlled, randomized phase 3 study. In this study, 600 patients with stage 3b/4 CKD were randomised in different locations including the United States, Europe, and Asia. Participants were randomly assigned to receive either a placebo or ocedurenone allowing researchers to assess blood pressure-lowering efficacy of the drug over the placebo. Regardless of their substantial investment, the company was unsuccessful in demonstrating ocedurenone’s capability to reduce blood pressure over the placebo after 12 weeks of treatment. If the drug had not demonstrated unsuccessful effects after the set period of time, the study would have proceeded to reassess blood pressure reduction for an additional 48 to 52 weeks, to test its long-term efficacy.

CLARION-CKD followed a similar approach as that of the phase 2b BLOCK-CKD study, where bardoxolone methyl was also tested for its efficacy and safety in treating patients with type 2 diabetes at no specific disease stage. The study was in fact successful in demonstrating blood pressure reductions with a minimal risk of hyperkalemia. Furthermore, drugs in the same therapeutic class such as enalapril and losartan have shown efficacy in treating hypertension and CKD patients due to their well established mechanism of renin-angiotensin-aldosterone system (RAAS), a regulatory system that controls blood pressure and fluid balance, compared to Novo’s ocedurenone. 

Despite the unfortunate outcomes of Novo Nordisk’s ocedurenone not meeting CLARION-CKD phase 3 trial’s primary endpoint, the drug was still able to show potential in treating hypertension and other related chronic diseases. Looking ahead, Novo’s decision to recognize an impairment loss demonstrates the risks and uncertainties encountered in clinical trials. Moving forward, the pharma giant will recalibrate its focus to gain better regulatory strategies to carry out future clinical studies and ensure beneficial results.

Author

Denisse Sandoval