There were no drug-drug interactions between the investigational antifibrotic cudetaxestat by Blade Therapeutics and the approved nintedanib for idiopathic pulmonary fibrosis (IPF) treatment, according to the results of an in vivo pharmacokinetic study.

The study also showed that another investigational autotaxin inhibitor, GLPG-1690 (ziritaxestat) by the pharmaceutical company Galapagos NV, significantly increased the plasma concentration of nintedanib, Blade Therapeutics announced in a news release.

Cudetaxestat is a noncompetitive, reversible autotaxin inhibitor. Blade Therapeutics completed a phase 1 clinical trial investigating the relative bioavailability of a tablet formulation of cudetaxestat to an oral solution formulation.


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The results of the trial showed that the pharmacokinetic and pharmacodynamic profiles of the 2 formulations were comparable. They also had a favorable tolerability profile with no severe adverse events.

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“We believe that these are important data that help inform our step-wise approach to advance the clinical development program for cudetaxestat,” said Wendye Robbins, MD, the president and chief executive officer of Blade said in the press release. 

The company is currently conducting another phase 1 clinical trial in healthy volunteers. This will assess the effect of cudetaxestat on the pharmacokinetics for CYP450 enzymes from a combination of probe substrates, the major drug-metabolizing enzymes in humans. The primary outcome measures are the areas under the drug concentration time curve from time 0 to the last measurable concentration and the maximum observed drug concentration.

The study already enrolled 16 participants and is no longer recruiting. It is expected to be completed in November 2021. Blade also plans to initiate another phase 1 trial to assess cudetaxestat on the pharmacokinetics of nintedanib and pirfenidone, another drug approved for IPF.

Autotaxin is a key enzyme responsible for stimulating biological processes leading to fibrosis. High levels of autotaxin can therefore lead to various fibrotic diseases, including IPF. Inhibiting the autotaxin pathway has been validated in IPF.

References

Blade Therapeutics announces positive data from preclinical drug-drug interaction study of cudetaxestat, a non-competitive autotaxin inhibitor in clinical development for idiopathic pulmonary fibrosis (IPF). News release. Blade Therapeutics; September 20, 2021.

Healthy volunteer study comparing tablet and oral solution formulations. US National Library of Medicine. Last updated July 15, 2021. Accessed September 22, 2021.

Drug-drug interaction (DDI) study in healthy volunteers. US National Library of Medicine. Last updated August 9, 2021. Accessed September 22, 2021.