Arrowhead Pharmaceuticals has voluntarily paused Phase I/II AROENaC1001 clinical trial of its investigational RNA interference (RNAi) therapy, ARO-ENaC, for treating cystic fibrosis (CF).
The move comes after the company received an initial update from a chronic toxicology study underway in mice that showed unpredicted local lung inflammation signals.
Regulatory agencies and institutional review boards were alerted on the trial pause while Arrowhead advised investigators to stop new screening, enrolment and dosing with the treatment until further data from the rat study becomes available.
A chronic primate toxicology study is progressing, and this data will also be analysed to decide on the Phase I/II trial.
The Phase I/II AROENaC1001 dose-escalating study is designed to assess the safety, tolerability and pharmacokinetic effects of ARO-ENaC in healthy subjects, along with the safety, tolerability and efficacy of the treatment in CF patients.
Arrowhead Pharmaceuticals chief medical officer Javier San Martin said: “While we have not seen any concerning safety or tolerability signals in subjects enrolled in the AROENaC1001 study, out of an abundance of caution, we have decided to pause new screening, enrolment, and any further dosing of investigational ARO-ENaC in the study while we await additional information from ongoing nonclinical toxicology studies.
“After we receive the full data from these studies, we will assess whether there is an acceptable path forward for further clinical investigation.”
The company’s president and CEO Christopher Anzalone added that the chronic rat toxicology study findings may not directly impact the Phase I trial’s safety.
However, Arrowhead intends to gain improved insights into the findings and their potential effect on humans prior to treating more patients.
The company will now continue to develop other eight clinical drug candidates in its pipeline, along with preclinical works such as additional lung-targeted programmes.
In August 2020, the company started dosing patients in a Phase Ib AROHIF21001 clinical trial of ARO-HIF2 to treat clear cell renal cell carcinoma (ccRCC).