▎ WuXi AppTec content team editor
Recently, an IDH1 inhibitor, Avonib Tablets (trade name: Toskovo), was approved for marketing by the State Drug Administration of China (NMPA) for the treatment of adult patients with recurrent or refractory acute myeloid leukemia (R/R AML) in adults with IDH1 susceptible mutations.
Screenshot source: NMPA official website
Public information shows that the approval of avonib tablets for marketing will provide new precision treatment options for patients with acute myeloid leukemia.
About leukemia
Leukemia is a common hematologic malignancy, which can be divided into acute leukemia (AL) and chronic leukemia (CL) according to the degree of differentiation maturity of leukemia cells, the natural course of the disease, and the main cell series involved:
Acute leukemia (AL), which develops rapidly and has a natural course of only a few months, can be divided into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML);
Chronic leukemia (CL), which develops slowly and has a natural course of several years, can be divided into chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), and rarely, leukemia.
In China, there are more patients with acute leukemia than chronic leukemia (about 5.5:1), of which acute myeloid leukemia is the most, with an incidence of 1.62/100,000, followed by acute lymphoblastic leukemia, with an incidence of 0.69/100,000.
In recent years, with the aging of the population, the incidence of acute myeloid leukemia in China has shown an increasing trend year by year. According to data released by the International Agency for Research on Cancer (IARC), 85,000 new leukemia patients were added to China in 2020, resulting in 62,000 deaths. About 60% of new leukemia patients are acute myeloid leukemia, and in these patients, about 6% to 10% carry IDH1 mutations.
Historically, existing treatments for patients with acute myeloid leukemia with IDH1 mutations have been limited, with a low 5-year survival rate and poor quality of life.
Image credit: 123RF
About relapsed or refractory acute myeloid leukemia
The Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Malignant Hematological Diseases 2020 point out that any of the following is relapsed or refractory acute myeloid leukemia:
Treatment of initial patients with 2 ineffective courses of treatment after a standard regimen;
Patients who, after complete remission (CR), after consolidation intensification therapy, relapse within 12 months;
Patients who relapse after 12 months, but do not respond to conventional chemotherapy;
Patients with 2 or more relapses;
Patients with persistent extramedullary leukemia.
About Avonib
Avonib, an orally targeted inhibitor of the IDH1 mutant enzyme, was approved for marketing in China based on a Chinese-registered bridging study, CS3010-101. This study aimed to evaluate the pharmacokinetic profile, pharmacodynamic profile, safety profile, and clinical efficacy of avonib oral therapy in Chinese patients with IDH1 susceptible mutations, relapsed or refractory acute myeloid leukemia in adults.
The results of the study showed that avonib showed excellent clinical efficacy and good tolerance in the treatment of adults with recurrent or refractory acute myeloid leukemia in China with susceptible IDH1 mutations:
Among the 30 assessable patients, the primary efficacy endpoint, complete response and complete response with partial haematological recovery (CR+CRh), was 36.7% (11/30, 11 patients achieved complete remission), the median time to CR+CRh was 3.68 months, and the sustained response rate at 12 months cr+CRh was 90.9%.
Two patients underwent hematopoietic stem cell transplantation (HSCT) after achieving a complete remission or a complete remission with partial hematologic recovery.
The median event-free survival (EFS) was 5.52 months and the median overall survival (OS) was 9.10 months.
Avonib is well tolerated and controllable in safety. The incidence of adverse events (TEAE) above level 3 was 86.7%, and the incidence of TEAE leading to permanent discontinuation was 10% ; no new safety signals were found, and adverse events of special concern could be effectively monitored and controlled through protocol guidance and clinical routine management.
In the UNITED STATES, Avonib has been approved for treatment for a number of indications, including adults with recurrent or refractory AML with IDH1 mutations, newly diagnosed adults with IDH1 susceptible mutations who are ≥ 75 years of age or who are unable to use intensive chemotherapy because of other comorbidities, and adults with locally advanced or metastatic cholangiocarcinoma with IDH1 mutations.
We expect that with the approval of avonib in China, it will bring new treatment options and hope to more patients with acute myeloid leukemia, helping them improve their quality of life and prolong their lives."