AML's new drug development accelerates! BMS Aza cytosine was approved to break the deadlock in intensive immunotherapy admission.

AML, one of the siestring blood tumors in drug development compared to other tumors, has finally reached a new breakthrough this year when Onureg was approved by the FDA on September 1, 2020, becoming the first and only maintenance therapy currently available for patients with remission AML, while the development of new AML drugs is accelerating.
AML major gene mutation type and approved targeted drug AML is a genetic heterogeneity malignant tumor originating from cloned hematopoietic stem cells, relatively rare but very deadly tumor, the United States each year 20,000 new patients, about 10,000 patients died, five-year survival rate as low as 28.7%.
the pathogenesis of AML is not known, with the development of molecular credit type, it is currently believed that molecular mutations can contribute to leukemia through two mechanisms.
One is a molecular change that activates the signal transductor path, which affects the survival, proliferation and differentiation of hematopoies, which includes members of the type III. type-lime Tyrosine kinase FLT3 or RAS family; Ingredients, which are regulated by the observational genetics, lead to damage to hematocyte differentiation, which includes the CCAAT/enhancer binding protein α gene (CEBPA), the nuclear phosphorus protein gene (NPM1), and isocit acid dehydrogenase (IDH), which is involved in a variety of metabolic and oscemic genetic cell processes.
AML main molecular mutation type and proportion AML patients usually first "induced chemotherapy", commonly used 7 plus 3 standard chemotherapy (agasin 7 days plus 3 days of cyclocyclyc antibiotics), followed by intensive reinforcement chemotherapy or hematopoietic stem cell transplantation treatment.
only a few AML patients were able to successfully perform a bone marrow transplant, and most were not only likely to be unresponsive to chemotherapy but would gradually progress into relapsed or resoicative AML, with a very low five-year survival rate.
has been approved for the market of targeted drug AML new drug clinical development trend from the last 5 years AML new drug approved in the United States, we can also see that AML new drug clinical development trend is mainly three categories.
is used in combination with standard therapies to get into first-line treatment.
According to the clinical classification of patients - suitable for intense chemotherapy and not suitable for intense chemotherapy groups, for people suitable for intense chemotherapy, the choice of 7-3 standard chemotherapy as the first-line treatment of induced chemotherapy is difficult to shake, midostaurin and gemtuzumab ozogamicin used a combination of "7-3" therapy strategy.
similar, glasdegib and venetoclax are also used in combination with low-intensity chemotherapy, such as agasin, for people who are not suitable for intensive chemotherapy.
and standard chemotherapy as a first-line treatment of the new drug two is to challenge the relapse difficult to treat the population, this population because the traditional treatment CR rate is not high, so the new treatment in the one-arm trial CR rate has improved, there is a chance to be approved, so that more new target drugs, immunotherapy into the field of AML drug treatment development.
IDH1/2, FLT3 inhibitor targeted therapy will be limited in clinical use of special gene mutation population, but because the target efficacy has been confirmed, many companies are currently developing the next generation of targeted drugs, such as IDH1/2 inhibitor vorasidenib, third generation FLT3 inhibitor FF-10101 and so on.
3 is post-remission maintenance therapy, a treatment strategy derived from some AML patients after receiving intensive induction chemotherapy to achieve remission, but the response time is not continuous, resulting in a recurrence of the total survival period is short, so the post-available maintenance treatment may improve the survival of patients.
This treatment strategy has not been proven for decades, until BMS Onureg (Azadesin 300mg tablet) became the first therapy approved for first-line maintenance therapy to significantly improve total lifetime (OS, primary endpoint) compared to placebos .24.7 months vs 14.8 months.
immune therapy to the market Although immunosuppressants are not as effective in AML, many companies are still actively exploring the future of immunotherapy in AML, including Forty Seven's single-anti-magrolimab target CD47 OrR reached 64% in phase IB trials with azacitidine for primary treatment of AML patients, especially in AML patients with TP53 mutations, and 78% in patients with ORR, which has been eligible for FDA fast track.
because AML cell high expression CD123 is associated with primary treatment failure and poor prognostication, ImmunoGen's CD123-ADC IMGN632, MacroGenics' CD123×CD3 dual anti-Fltuzumab and Mustang Bio's CD123 CAR T cell therapy are all being explored for the relapse-resistant AML population.
TIM-3 is an inhibitory subject expressed on the surface of immune cells and myeloid leukemia cells.
its expression levels were associated with the severity of acute myeloid leukemia (AML) and MDS.
's TIM-3 monoantigen MBG453 is also conducting phase II clinical trials with AML patients who are not suitable for chemotherapy in combination with azacitidine and venetoclax.
Nature predicts that the market for AML's main therapeutic drugs will expand rapidly with the approval of multiple targeted drugs and increase treatment options for multiple AML populations, resulting in a decrease in the market share of low-methylated chemotherapy such as agalycosides.
At the same time, regulators have become relatively open to the highly unsecured AML treatment market, and while total survival OS is still the gold standard for primary AML treatment, there are trials that use event-free survival (EFS), ORR rates as the primary endpoint indicators, and at an earlier stage initiate randomized controlled trials with large sample sizes to obtain more adequate efficacy and safety data to obtain faster review and approval of new drugs.
, there will be a place for immunotherapy in the AML drug market.
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