Cudetaxestat Did Not Interact with Ofev in Animal Study

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Cudetaxestat (BLD-0409), an investigational treatment for idiopathic pulmonary fibrosis (IPF) being developed by Blade Therapeutics, does not interact with the approved IPF treatment Ofev (nintedanib), according to research done in rats.

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

Cudetaxestat works by blocking the activity of autotaxin, an enzyme that makes a pro-fibrotic signaling molecule and is commonly overactive in people with IPF. By blocking autotaxin, cudetaxestat is expected to reduce fibrosis, or tissue scarring, by dampening these pro-fibrotic signals.

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New data came from a preclinical study, conducted at an independent lab, in which 18 male rats were first given Ofev for four days. Then, nine rats were treated for an additional week with cudetaxestat in addition to Ofev, while the other nine animals were given ziritaxestat (GLPG1690) alongside Ofev.

While no evidence of noteworthy interactions were found between cudetaxestat and Ofev, results showed that co-administering ziritaxestat increased Ofev’s levels in the animals’ bloodstream.

Like cudetaxestat, ziritaxestat is an inhibitor of autotaxin. It was being developed by Galapagos and Gilead Sciences as a potential therapy for IPF, but the companies stopped its development earlier this year after interim data from two Phase 3 clinical trials indicated the therapy’s risks outweighed its potential benefits.

“Based on preclinical in vivo [in living animals] and in vitro [in lab-grown cells] studies conducted to date with cudetaxestat, we believe there is low potential risk for drug-drug interactions with either of the approved drugs for IPF — pirfenidone [Esbriet] or nintedanib [Ofev],” Robbins said.

Earlier this year, Blade was given authorization to launch a Phase 1 trial (NCT04939467) in the U.S. testing the potential pharmacological interactions between cudetaxestat and either Ofev or Esbriet in healthy volunteers. Results from this study, which is expected to launch later this year and to conclude in the first half of 2022, will be used to inform the design of a future Phase 2 trial evaluating the safety and efficacy of cudetaxestat in people with IPF.

Blade recently completed a Phase 1 trial (NCT04814472) that compared the properties of a new tablet formulation of cudetaxestat to the original oral solution version of the medication in healthy volunteers. Results showed that the two formulations were comparable in terms of their pharmacological properties and safety profile.

The company also is conducting another Phase 1 trial (NCT04814498) to assess the interactions between cudetaxestat and a combination of probe substrates for CYP450 enzymes, which are liver enzymes important for processing certain medicines. According to Blade, this study is on track to be completed later this year.

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