Oryzon Genomics, a clinical-phase biopharmaceutical company focused on epigenetics for the development of therapies in diseases with significant unmet medical needs, today presents new positive efficacy data from the Phase IIa clinical trial ongoing with iadademstat in acute myeloid leukemia (AML), ALICE, in the EHA-2021 Virtual Congress of the European Hematology Association, in a communication in electronic format entitled “ALICE MAINTAINS HIGH CLINICAL RESPONSE RATES SUPPORTING THE EFFICACY OF IADADEMSTAT COMBINATION WITH AZACITIDINE IN AML MANAGEMENT”.
At the cut-off date of the data included in this communication, 27 patients had been enrolled in the study, 26 of whom met the inclusion criteria; of these, 18 patients were evaluable for efficacy according to protocol and 2 more patients were still in their first cycle. The clinical efficacy evidence continues to be strong and consistent with previously reported data, with a objective response rate (ORR) 83% (15 of 18 evaluable patients); of these, 67% were complete remissions (10 CR / CRi) and 33% were partial remissions (5 PR). Among these responses, a patient with type M5b AML (a particularly aggressive subtype with a poor prognosis) and with an adverse genetic prognosis that reached an HR in 29 days stands out. The mean time to response (TTR) in the trial remains short (29 days).
With rates of historical response of 28% (19% CR / CRi and 9% PRs) in this population when treated with azacitidine alone, these results suggest a strong synergy between iadademstat and azacitidine used in combination.
The duration of the observed responses is long, with 60% of CR / CRi with durations of more than 6 months (an additional 30% are still recent CR / CRIs and in the maturing phase). The longest remission at the cut-off date of the data included in this EHA-2021 poster was 858 days in a patient who continues to be independent of transfusions and with negative residual disease. Another four patients have exceeded one year of response (three still in response). Patients with longer treatment periods also improved or exceeded their dependence on blood transfusions, with 50% of patients achieving transfusion-independent CR / IR.
The Dr. Carlos Buesa, CEO of Oryzon, has commented: “After 30 months of study and with a growing number of patients, the data from ALICE is really very positive, we are confirming a robust and high percentage of responses. In addition, they are very long responses in the time, which results in a longer survival of responders. Considering the difference in mechanisms of action between pro-apoptotic BCL2 inhibitors and the pro-differentiating agent iadademstat, we believe that combination therapies with iadademstat could increase therapeutic options first-line AML patients, as well as refractory or intolerant patients who have received first-line BCL2 inhibitors. “
The combination of iadademstat with azacitidine continues to show a good safety profile with only two serious adverse events reported as probably related to treatment. The most frequent events continue to be a decrease in the platelet and neutrophil count. Beyond the hematological impact, expected according to the pharmacological mode of action and previously reported in ASH-2020 and EHA-2020, the combination continues to appear safe and well tolerated by elderly patients with AML.
The objective of ALICE trial is to provide information that enables a wider use of iadademstat in leukemia. ALICE is designed as an open-label, single-arm intervention study with iadademstat in combination with the standard treatment azacitidine in elderly patients with newly diagnosed AML and is being carried out in eight Spanish hospitals. The study will recruit up to a maximum of 36 patients.