Kura death deals novel leukaemia mechanism a blow

Kura dealt the nascent menin inhibition space a blow today with news of a patient death in the phase 1b Komet-001 trial of KO-539. The study has now been paused. The cause of the death was probably differentiation syndrome, a potentially life-threatening complication seen with so-called differentiation agents used to treat various leukaemias. Differentiation syndrome is “absolutely a class effect” of menin inhibitors, Kura’s chief executive, Troy Wilson told analysts on a call today, describing it as “part and parcel of this mechanism of action”. Other cases of DS seen with menin inhibitors have been mild and manageable, he said, adding that the patient had very extensive disease, having failed four prior treatments. But the fact that mitigation strategies for DS were already in place, yet the death still happened, is concerning; that the patient was being treated at the lower of two doses is another worry. Kura remains committed to menin inhibition, executives insisted, but at the very least this means a delay for KO-539, and Kura's stock fell 17% this morning. Others working in this space will be looking on nervously, particularly Syndax, which has had its own problems with the menin contender SNDX-5613. 

Trials of the menin inhibitors: a nascent pipeline
Project Company Trial details 
Early clinical 
KO-539 Kura Oncology Ph1/2; 90 pts, AML, on clinical hold (NCT04067336)
SNDX-5613 Syndax  Ph1/2; 186 pts, AML, primary completion Jul 2022 (NCT04065399)
DS-1594 Daiichi Sankyo Ph1/2; 122 pts, AML & ALL, primary completion Nov 2022 (NCT04752163)
JNJ-75276617 Johnson & Johnson Ph1; 110 pts, AML & ALL, primary completion Dec 2023 (NCT04811560)
Preclinical
BMF-219 Biomea Fusion IND approved Sep 2021
Source: Evaluate Pharma & clinicaltrials.gov.

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