FDA Grants Breakthrough Therapy Designation for Kura’s Treatment for NPM1-Mutant AML

Rare Daily Staff

The U.S. Food and Drug Administration granted Breakthrough Therapy designation for Kura Oncology’s ziftomenib for the treatment of patients with relapsed/refractory NPM1-mutant acute myeloid leukemia.

Acute myeloid leukemia (AML) is the most common acute leukemia in adults and begins when the bone marrow makes abnormal myeloblasts (white blood cells), red blood cells or platelets. Despite the many available treatments for AML, prognosis for patients remains poor and a high unmet need remains. The menin pathway is considered a driver for multiple genetic alterations of the disease, of which NPM1 mutations are among the most common, representing approximately 30 percent of AML cases. While patients with NPM1-m AML have high response rates to frontline therapy, relapse rates are high and survival outcomes are poor, with only 30 percent overall survival at 12 months in the relapsed/refractory (R/R) setting.

Additionally, NPM1 mutations frequently occur with co-mutations in other disease-associated genes, including FLT3, DNMT3A and IDH1/2, with prognosis heavily influenced by the occurrence of co-occurring mutations. Adult patients with NPM1-m AML and select co-mutations and/or R/R disease have a poor prognosis, with median overall survival of only approximately 7.8 months in 2nd line, 5.3 months in 3rd line and 3.5 months following the 4th line2. There are currently no FDA-approved therapies targeting NPM1-m AML.

Ziftomenib is a novel, once-daily, oral investigational drug candidate targeting the menin-KMT2A/MLL protein-protein interaction for treatment of genetically defined AML patients with high unmet need.

In the KOMET-001 Phase 1 study, ziftomenib demonstrated an encouraging safety profile and tolerability with reported events most often consistent with features and manifestations of underlying disease. Clinical activity of ziftomenib as a monotherapy was optimal at the 600 mg daily dose and a 35 percent complete remission rate was observed in 20 patients with NPM1-mutant AML treated at the recommended phase 2 dose (600 mg). Ziftomenib has received Orphan Drug designation from the FDA for the treatment of AML.

The Breakthrough Therapy designation was based on data from Kura’s ongoing KOMET-001 clinical trial in patients with R/R NPM1-mutant AML. Breakthrough therapy is granted for a drug that treats a serious or life-threatening condition and for which preliminary clinical evidence indicates the drug may demonstrate substantial improvement on a clinically significant endpoint(s) over available therapies. The designation is intended to expedite development and review of drugs, including an organizational commitment by FDA senior managers and experienced review staff as well as eligibility for rolling review and priority review.

“NPM1-mutant AML represents approximately 30 percent of new AML cases annually, and this designation reflects that NPM1-mutant AML is a disease of significant unmet need for which there is no approved targeted therapy as well as the fact that ziftomenib offers potential to demonstrate substantial improvement over available therapies,” said Troy Wilson, president and CEO of Kura Oncology.

Kura is on track to complete the registration-directed trial of ziftomenib in R/R NPM1-mutant AML by mid-2024. Ziftomenib is also being evaluated in combination with current standards of care, including venetoclax/azacitidine or cytarabine plus daunorubicin (7+3) in NPM1-mutant and KMT2A-rearranged AML and with gilteritinib, FLAG-IDA or LDAC in NPM1-mutant and KMT2A-rearranged AML.

Photo: Troy Wilson, president and CEO of Kura Oncology