FDA lifts partial hold on Kura's Phase Ib AML program as biotech redoubles mitigation efforts
Kura Oncology is clear to resume studies for its early-stage leukemia program after the FDA lifted a clinical hold Thursday afternoon.
Regulators had placed the hold on a Phase Ib study of KO-539, an experimental oral treatment for some genetic subsets of acute myeloid leukemia last November after a patient died while taking the drug. Kura expects to begin enrolling patients again imminently, CEO Troy Wilson told Endpoints News.
“The physicians tell us they have patients waiting,” Wilson said. “And the key over the next couple of weeks will be how do we get as many sites as needed up as fast as possible.”
The death is thought to have resulted from differentiation syndrome, a condition that can often pop up during AML treatments. Wilson, attempting to calm investor nerves last November, said the syndrome is a class-wide issue for menin inhibitors such as KO-539 and can usually be managed through corticosteroid treatments.
It was not known in November whether the drug was linked to the death and the patient’s family did not consent to an autopsy, making it difficult to determine the cause, Wilson said at the time. The patient had advanced disease, having previously failed four lines of therapy, and was taking the lower dose being studied.
The cause of death is still undetermined, Wilson said Thursday, but he noted that in FDA correspondence, regulators focused less on the death itself and more on how Kura planned to mitigate future differentiation syndrome cases. Kura says KO-539 is designed to induce differentiation of leukemic cells, and such cases are evidence it’s working as planned.
Now, Kura is implementing two significant changes to its mitigation strategy, Wilson said. First, it will regularly monitor patient cell counts in the first few weeks of treatment using blood samples. And second, if the counts go above a certain threshold at any time, physicians must stop administering the drug until symptoms abate.
“Previously, we had left that up to their discretion,” Wilson said of potential treatment withdrawal. “The protocol still gives the physicians a tremendous amount of discretion in treatment, but there is a point where … if the physician sees this, and they’re having trouble controlling it, now they get to a point where they have to withdraw our drug.”
There are other minor changes to the study, but most largely deal with small language tweaks in the protocols, he added.
Such a mitigation strategy was one of three things asked for by the FDA, Wilson outlined two months ago, in addition to reviewing safety data and reaffirming why Kura selected the doses being studied. Kura’s study will be allowed to resume at the same dosing levels — 200 mg daily at the low dose and 600 mg daily at the high dose.
There’s no timeline yet for when the Phase Ib study will read out data, nor for when Kura will have selected the appropriate Phase II dose. Given the aggressive nature of relapsed and refractory AML, Wilson said he couldn’t rule out another patient death in the future. But as with many treatments in advanced cancers, Wilson argued the benefit outweighs the risk.
“These patients have weeks or possibly days to live. I don’t think we can give an ironclad guarantee that it would never happen again,” he said. “You do everything you can to try to give the patient the best chance for survival, and the best chance to put the disease in remission.”