AML Therapeutics Shift Toward Earlier Combination Regimens

Menin inhibitor use in relapsed AML is moving earlier and into combination regimens. On their third-quarter 2026 earnings calls on November 2 and November 10, Syndax Pharmaceuticals (SNDX) and Kura Oncology (KURA) said physicians are giving their menin inhibitors at earlier relapses alongside other drugs, and that patients who respond then stay on the drug as maintenance therapy [1][2].

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How combination use carries patients to transplant and maintenance

Menin inhibitors started out as late-line, single-agent salvage therapy. They are oral targeted drugs for relapsed or refractory acute myeloid leukemia (AML), a blood cancer in which blood-forming cells in the bone marrow grow out of control and few options remain after relapse. They work only in patients whose leukemia carries an NPM1 mutation or a KMT2A rearrangement. Syndax sells Revuforj (revumenib); Kura sells Komzifti (ziftomenib). Under single-agent salvage use, analysts have modeled revenue on a therapy duration of about five months [2].

What physicians have changed is when and with what the drug is given. They add it to the common venetoclax-plus-azacitidine backbone, or pair it with a FLT3 inhibitor in patients who also carry a FLT3 mutation, and they use it more often at first or second relapse [1][2]. Once patients respond earlier and more deeply, there are two routes to keep them on the drug. Some go on to a stem-cell transplant and resume the drug afterward. Others reach MRD negativity, meaning highly sensitive tests no longer find residual leukemia cells, and simply stay on the drug as maintenance. The two companies sell different drugs and draw on different data sources, yet they report the same direction.

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Combination use reaches 40-50%, and NPM1 patients move to post-transplant maintenance

Syndax said the share of NPM1 patients who reach transplant has risen to about 40%, against about 11% in clinical trials. About 75% of use is now at first or second relapse, and about 40% is combination treatment. Half of transplanted patients resume the drug after transplant, and the post-transplant group is already averaging at least nine months of therapy [1]. One quarter earlier, management said most NPM1 patients do not go to transplant [3]. Syndax estimates its NPM1 business accounted for more than 35% of the $61 million in Revuforj net revenue this quarter [1].

Kura described a different maintenance route. Its claims data show that nearly half of Komzifti patients receive it in combination, mainly with venetoclax plus azacitidine or with FLT3 inhibitors, up from about 40% in the first quarter [2][4]. Kura's chief medical officer said most patients who reach MRD negativity can avoid the added risk of transplant, and that patients on combination regimens drop the backbone therapy and continue on Komzifti alone as post-consolidation maintenance [2]. One route runs through transplant and the other mostly avoids it, but both point to the same result: responding patients stay on therapy longer than under single-agent salvage use.

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Why therapy duration now matters as much as new patient starts

Revenue for these drugs is roughly the number of new patients multiplied by how long each patient stays on therapy, and earlier combination use and maintenance raise the second factor. Syndax's CEO said transplant patients typically go to transplant within about three months of starting the drug, pause for two to five months, then resume, so 2027 is when the largest effect should show [1]. Kura's CEO said the company wants menin inhibitors used in every conceivable combination in every line of therapy [2]. If that is where the market goes, whether later entrants can be combined with standard regimens may decide how much share they win.

This view has clear limits. Kura's CEO said NPM1 patients are older and more fragile and much less likely to reach transplant, which contradicts Syndax's account. A TD Cowen analyst said a five-month-duration model produces more prescriptions and higher revenue than Kura has reported, so longer duration is not yet visible in Kura's revenue [2]. Syndax's chief commercial officer also said the effect may be specific to Revuforj rather than true of the whole class [1]. Metrics to track are each company's combination share, the share of patients resuming after transplant and average therapy duration.

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Companies exposed to this change

• Kyowa Kirin (4151.T): It shares US profits and losses on Komzifti 50/50 with Kura, so any increase in duration per patient would flow to its share in the same proportion [5].
• Sumitomo Pharma (4506.T): Its enzomenib is a menin inhibitor in a registrational study that includes combination cohorts with venetoclax plus azacitidine and with gilteritinib, so it is entering a market where combinability and duration have started to set share [6].
• Astellas Pharma (4503.T): It owns the FLT3 inhibitor gilteritinib, one of the combination partners Kura names. More combination use at earlier relapses could add gilteritinib starts, partly offset when patients drop the backbone in maintenance [4].

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Sources

[1] Drillr · Syndax Pharmaceuticals (SNDX) · 2026-11-02 · Q3 2026 earnings call

[2] Drillr · Kura Oncology (KURA) · 2026-11-10 · Q3 2026 earnings call

But what I am sure of is that monotherapy is no longer the story. And we've moved on to combination.

[3] Drillr · Syndax Pharmaceuticals (SNDX) · 2026-08-04 · Q2 2026 earnings call

[4] Drillr · Kura Oncology (KURA) · 2026-05-12 · Q1 2026 earnings call

[5] Drillr · Kura Oncology (KURA) · 2026-05-12 · Form 10-Q for fiscal Q1 2026 (note on the Kyowa Kirin collaboration and license agreement)

[6] OncLive · FDA grants breakthrough therapy designation to enzomenib in R/R KMT2A-rearranged acute leukemia · 2026-10-26 · Industry news · https://www.onclive.com/view/fda-grants-breakthrough-therapy-designation-to-enzomenib-in-r-r-kmt2a-rearranged-acute-leukemia

This article only highlights industry changes and companies that may be overlooked. It is not a stock recommendation.