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FDA suspends trials of Kura’s Leukemia drug KO-539 due to one death.
After a patient died due to a serious adverse event related to the mechanism of action of oral drugs, the U.S. FDA suspended an early cancer trial by Kura Oncology.
This means that no more patients will be enrolled in the trial before the FDA approves it.
Kura management said in a conference call on Wednesday morning that the regulator’s request for information was “not complicated” and the suspension should be “relatively short”.
According to the announcement issued by Kura, the FDA has suspended the phase 1b trial of KOMET-001, which evaluates KO-539 for the treatment of patients with relapsed or refractory acute myeloid leukemia (AML).
The company recently reported to the FDA a grade 5 serious adverse event (patient death) that may be related to differentiation syndrome (DS), and the FDA made the above decision.
KO-539 is a potent and selective menin inhibitor that is currently being developed for the treatment of AML, including AML patients with NPM1 mutations or KMT2A rearrangements.
KO-539 can block the interaction between menin and KMT2A/MLL, which together are essential for the survival, growth and proliferation of certain leukemia cells.
Preclinical data supports the conjecture that KO-539 targets epigenetic disorders and eliminates certain barriers to cell differentiation, thereby driving anti-tumor activity.
KO-539 has the potential to solve about 35% of AML, including NPM1 mutant AML and KMT2A rearranged AML.
At present, patients who have been enrolled in the above-mentioned KOMET-001 phase 1b study can continue to receive KO-539 treatment, but they cannot be enrolled in other patients until part of the clinical suspension is lifted.
Kura is working closely with the FDA and field investigators to resolve this issue as quickly as possible.
DS is a known targeting effect associated with differentiation-inducing therapeutic drugs (differentiation inducers) in the treatment of AML.
Among patients treated with such drugs, up to a quarter of patients will experience this adverse event.
DS is characterized by unexplained fever, acute kidney injury, hypotension, weight gain, and other harmful effects.
DS adverse events have been included in the black box warning of Tibsovo, an approved AML drug by Agios Pharmaceuticals, which was approved in July 2018.
In addition, DS Xospata, Astellas’ AML drug, also has a 1% incidence.
Kura’s management described the syndrome as “part of the drug’s mechanism of action,” and its leadership stated in a conference call discussing the news that the occurrence of the syndrome “should not surprise anyone.” The company and its on-site investigation The staff has developed a mitigation strategy for the syndrome, and the number of other patients experiencing the syndrome is “relatively small”, and these cases are “controllable and resolved with steroids.”
Kura disclosed that the patient who died had previously experienced 4-line treatment failure and started to take a 200mg dose of the drug in the trial.
Kura management stated that the FDA requires “three key pieces of information”, including a safety database review, a description of the fatal syndrome mitigation plan, and reasons for the choice of 200mg and 600mg doses.
Dr. Troy Wilson, President and CEO of Kura, said in a statement: “Based on all preclinical and clinical data, we still believe that KO-539 has the potential to address significant unmet medical needs in AML patients, including NPM1 mutations and KMT2A rearranges patients.”
1.FDA halts phase 1b Kura Oncology trial in acute myeloid leukemia following patient death
2.Kura Oncology Provides Update on Phase 1b Study of KO-539 in Acute Myeloid Leukemia | Kura Oncology, Inc.
FDA suspends trials of Kura’s Leukemia drug KO-539 due to one death
(source:internet, reference only)