Adding blood cancer treatment to AML care safe, effective in 2 early trials
Iadademstat being tested for both newly diagnosed and hard-to-treat leukemia
Written by |
Adding iadademstat, an experimental blood cancer drug, to standard of care treatment for acute myeloid leukemia (AML) appeared to be safe and effective in two early clinical trials involving AML patients, according to its developer Oryzon Genomics.
The smaller of these trials, dubbed ALICE-2 (NCT06357182), is focusing on individuals with newly diagnosed AML. Several participants have genetic mutations linked to more severe or high-risk forms of this type of blood cancer. The Phase 1b trial is still recruiting patients at its single site in Portland, Oregon.
The other study, FRIDA (NCT05546580), conducted at 13 locations, investigated the therapy candidate in people with a specific AML-causing mutation. This Phase 1 trial involves AML patients in whom the disease relapsed, or returned after initial treatment success, as well as those whose leukemia is refractory, or did not respond to therapy.
“We are encouraged by the sustained strength and consistency of the data from both the ALICE-2 and FRIDA trials,” Carlos Buesa, CEO of Oryzon, said in a company press release announcing “positive clinical data.”
“We anticipate reporting final data by year-end and advancing toward a potential registrational study in first-line AML by 2027, with a focus on adverse-risk populations,” Buesa said. Registrational studies are those designed to provide robust results that, if positive, could be used to apply for a therapy’s approval.
Updated results from both trials were presented in two posters at the European Hematology Association 2026 Annual Congress, held June 11-14 in Stockholm and virtually.
AML is the most common type of leukemia in adults. It occurs when immature blood cells grow out of control in bone marrow, the spongy tissue inside some bones. These cancerous cells eventually travel into the bloodstream, causing symptoms such as easy bleeding and bone or joint pain. Certain genetic mutations can increase the risk of AML.
Several techniques are available for treating AML, including chemotherapy, as well as more targeted medications. For some individuals, stem cell transplants can replace diseased cells in bone marrow, promoting recovery. However, this isn’t always an option, and eligibility may depend on overall health and AML severity.
Many people with AML don’t respond completely to treatment or, after an initial period of remission, in which cancer activity is reduced, later relapse. As such, there is a need for new treatments, according to the developer.
Iadademstat designed to be given alongside existing therapies
Oryzon designed iadademstat as an add-on for existing standard therapies. The medication targets LSD1, a protein that helps regulate cell growth; its dysfunction can contribute to blood cancers such as AML. Researchers believe that blocking LSD1 could help make blood cancer treatment more effective.
ALICE-2, now more than 80% enrolled, according to the developer, is evaluating the therapy in AML patients who are newly diagnosed. Participants are receiving iadademstat alongside a targeted AML treatment that combines azacytidine (sold as Vidaza, with generics available) and venetoclax (sold as Venclexta and Venclyxto, with generics available).
“Historically, with azacitidine plus venetoclax, one third of first line AML patients do not respond, and the depth of response is variable, underscoring the need for novel triplet strategies, particularly for patients without targetable mutations,” said Ana Limón, PhD, Oryzon’s senior vice president of clinical development and global medical affairs.
In a poster titled “Updated safety and efficacy results of a Phase Ib investigation of the LSD1 inhibitor iadademstat (ORY-1001) in combination with azacitidine and venetoclax in newly diagnosed AML,” researchers presented data from 18 ALICE-2 participants. Five of these individuals had genetic mutations commonly associated with higher-risk disease.
In the ALICE-2 trial, treatment with the iadademstat [in combination with two other medications] has enabled a high proportion of patients to transition to [stem cell transplants], potentially improving long-term survival.
A total of 78% of the participants, including all with high-risk mutations, had a complete response (CR), meaning the cancer went away entirely, the researchers noted. The overall response rate (ORR), which includes both complete and partial responders, was 100%. Most complete responses occurred during the first cycle of treatment, per the developer.
“In addition to the high ORR and CR rates observed to date in the ALICE-2 trial, treatment with the iadademstat-azacitidine-venetoclax triplet has enabled a high proportion of patients to transition to [stem cell transplants], potentially improving long-term survival,” Limón said. To date, nine participants have received transplants.
The treatment’s was shown to be safe, according to Oryzon. Common severe adverse events included neutropenia, or low levels of neutrophils, a type of immune cell, with or without fever.
“The favorable safety profile and strong efficacy signals of iadademstat in newly diagnosed … AML patients reinforce our confidence in this combination approach, including within genomically defined adverse-risk populations,” Buesa said.
Tw0-thirds of FRIDA patients entered complete remission
FRIDA enrolled people with relapsed or refractory AML who have mutations affecting the FLT3 protein, which can cause overproduction of immune cells.
Data from that study were presented in a poster titled “Safety and efficacy of iadademstat plus gilteritinib in the FRIDA expansion cohort of FLT3-mutated relapsed/refractory acute myeloid leukemia.”
The researchers detailed results from FRIDA’s dose-expansion phase, in which patients received an optimal dose of iadademstat plus gilteritinib, an FLT3-targeting medication approved for FLT3-related AML.
To date, 23 participants have been dosed in this phase. Data were available for 18 participants, and showed that about two-thirds entered complete remission. The most commonly reported severe adverse events were neutropenia, with or without fever, and low counts of other blood cell types.
Overall, the safety and efficacy observed across both trials support further clinical development [of iadademstat for AML].
“The maturing data from both trials continue to reinforce the strength of LSD1 [suppression] as an add-on approach in AML,” Limón said. “Overall, the safety and efficacy observed across both trials support further clinical development.”
Oryzon is also developing iadademstat for other blood cancers and blood diseases, including sickle cell disease.
