Kura’s Komet fizzles

Kura Oncology’s chance to outdo its menin inhibitor rival Syndax has turned into a damp squib. While Kura claimed a win in its registrational Komet-001 study of ziftomenib in relapsed/refractory AML after market on Wednesday, the company declined to give detailed data, making it hard to gauge how ziftomenib might stack up against Syndax’s Revuforj.

Kura executives stressed during a conference call that the decision was aimed at preserving the results for a medical meeting in the second quarter, with ASCO the likely target. But investors clearly wanted more: the group’s stock sank 13% on Thursday morning.

The primary efficacy endpoint of Komet-001, whose registrational portion focused on NPM1-mutated patients, is complete remission plus CR with partial hematologic recovery (CRh). When pressed Kura’s chief executive, Troy Wilson, said the study had been designed to show a CR/CRh rate of 20-30%, and that it hit its endpoint.

Syndax’s drug, meanwhile, recently produced a CR/CRh rate of 23% in NPM1m relapsed/refractory AML. That readout also disappointment investors, but likely because of reports of the heart rhythm issue of QTc prolongation.

Ziftomenib, which is now partnered with Kyowa Kirin, has previously avoided this issue, but Kura also didn’t provide any safety data on Wednesday, only saying that these were consistent with previous reports. Wilson concluded: “We think the benefit/risk compares favourably with the competition.”

This will only become clear with presentation of the full results. Kura also plans a filing in the second quarter, putting ziftomenib on a similar timeline to Revuforj, which is heading to regulators in relapsed NPM1m AML in the first half. Syndax’s drug is already approved for second-line KMT2A-rerranged acute leukaemia, but Kura abandoned this setting some time ago.

First-line trials

Both companies are vying for a piece of the first-line market, and there are now more details on Kura’s plan here.

On Wednesday the group disclosed the design of two phase 3 front-line ziftomenib trials: Komet-017-NIC, studying a “non-intensive” combo with Venclexta plus azacitidine in NPM1m patients unfit to receive chemo; and Komet-017-IC, testing an “intensive” 7+3 chemo combo in both NPM1m and KMT2Ar fit patients.

Kura is focusing on NPM1m in the unfit setting because most patients with KMT2Ar disease currently receive intensive chemo followed by stem cell transplant, explained the group’s chief medical officer, Mollie Leoni. The endpoints also differ between the trials.

Notable trials of Kura’s ziftomenib

Source: company presentation & clinicaltrials.gov.

Leoni noted that in fit patients 7+3 chemo alone can produce response rates of 80-90%, and it’s “hard to show a significant improvement over that”. However, patients still often relapse, so Kura has chosen MRD negativity, which she said correlates with long-term survival.

Meanwhile, in unfit patients ven/aza produces a 40-60% CR rate so there’s room for improvement in that setting, she noted.

Kura isn’t saying yet when it hopes to file for accelerated approval, but again Syndax is on a similar track. The latter plans to start a pivotal trial of Revuforj plus ven/aza in first-line unfit patients (both NPM1m and KMT2Ar) in the first quarter; “multiple” front-line chemo combo trials will follow in 2025.

The first-line AML market is worth $7bn overall, according to Kura, meaning that any small differences between the projects could make a big difference in terms of sales.