Bristol Myers Squibb Receives Positive CHMP Opinion for Onureg® (Azacitidine Tablets) as First Oral Maintenance Therapy for AML Patients in First Remission

Apr 24, 2021 02:38 CST Updated 02:38

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Committee for Medicinal Products for Human Use

Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.

European Commission

The European Commission, abbreviated as the EU Commission, is a supranational body under the European Union. Within the EU political system, the European Commission primarily undertakes executive tasks, thus being roughly equivalent to the government in a national system. However, the European Commission has other functions as well. In particular, except for the few circumstances specified in the treaties, the European Commission is the only institution with legislative power in the EU legislative process.

April 23, 2021 News /BioValleyBIOON/ -- Bristol-Myers Squibb (BMS) recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending the approval of Onureg (azacitidine 300 mg tablets, CC-486) as a first-line oral maintenance therapy for the treatment of patients who have achieved complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) following induction therapy (with or without consolidation therapy), and who are not eligible for or have chosen not to undergo hematopoietic Stem CellsAcute Myeloid Leukemia (ASCT)Leukemia(AML) adult patients. The CHMP opinion will now be submitted to the European Commission (EC) for review, which typically renders a final decision within two months.

If approved,Onureg will become the first and only once-daily oral first-line maintenance therapy available in Europe for patients with a broad subset of AML in first remission.Following its market launch, Onureg will address the urgent unmet medical need for new maintenance therapy regimens in patients with acute myeloid leukemia (AML). Data from the pivotal QUAZAR AML-001 study demonstrated that, in patients with AML in first remission, Onureg as first-line maintenance therapy yielded significant benefits in overall survival (OS) and relapse-free survival (RFS) compared with placebo. Subgroup analyses showed consistent OS benefits among patients achieving complete remission (CR) or complete remission with incomplete hematologic recovery (CRi).

In the United States, Onureg was approved in September 2020FDAApproved for continued treatment of adult patients with acute myeloid leukemia (AML) in first remission, specifically: for continued treatment of adult AML patients who have achieved first complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) following intensive induction chemotherapy and are unable to complete intensive curative therapy (such as allogeneic stem cell transplantation [ASCT]). AML is one of the most common types of acute leukemia in adults.

It is worth mentioning that,Onureg isFDAThe first and only approved continuation therapy for AML patients in remission.Onureg was approved via the Priority Review pathway. Regarding dosing, Onureg may be continued until disease progression or unacceptable toxicity occurs. Due to significant variability in pharmacokinetic parameters, Onureg should not replace intravenous or subcutaneous azacitidine.

The active pharmaceutical ingredient of Onureg is CC-486 (azacitidine), an oral hypomethylating agent that incorporates into DNA and RNA, allowing for sustained epigeneticGeneticsRegulation. Currently, this drug is being developed as aEpigeneticsModifiers, for Various Blood TypesTumortreatment. The primary mechanisms of action of this drug are considered to be DNA hypomethylation and direct cytotoxicity against abnormal hematopoietic cells in the bone marrow. Hypomethylation may restore the normal function of genes critical for differentiation and proliferation.

Onureg - Chemical Structural Formula of Azacitidine

Acute myeloid leukemia (AML) is the most common type of acute leukemia. AML originates in the bone marrow but rapidly enters the bloodstream. Unlike normal blood cell development, in AML, the rapid accumulation of abnormal white blood cells in the bone marrow can interfere with the production of normal blood cells, leading to reduced levels of healthy white blood cells, red blood cells, and platelets. AML is a complex and heterogeneous disease associated with various genetic mutations, and if left untreated, the condition typically deteriorates rapidly.

NewDiagnosisAdult patients with AML typically achieve complete remission through induction chemotherapy, but many experience relapse and poor outcomes. Patients in remission urgently need a treatment regimen that can reduce the risk of relapse and prolong overall survival.

The CHMP’s positive opinion is based on the efficacy and safety results from the pivotal Phase III QUAZAR AML-001 study. This study evaluated the efficacy and safety of Onureg as first-line maintenance therapy in patients with newly diagnosed acute myeloid leukemia (AML) who achieved their first complete remission (CR or CRi) following intensive induction chemotherapy and were deemed ineligible for autologous stem cell transplantation (ASCT) at screening. The results demonstrated that, as first-line maintenance therapy, Onureg significantly improved overall survival (OS, the primary endpoint) by nearly 10 months compared with placebo (median OS: 24.7 months vs. 14.8 months; p=0.0009) and more than doubled relapse-free survival (RFS, the key secondary endpoint; median PFS: 10.2 months vs. 4.8 months; p=0.0001), representing improvements that are both statistically and clinically significant.

Noah Berkowitz, M.D., Senior Vice President of Hematology Development at Bristol-Myers Squibb, stated: “There is an urgent need in Europe for maintenance therapies that extend overall survival in patients with acute myeloid leukemia (AML), particularly oral regimens that can be administered at home. Although many patients with AML achieve remission through induction therapy, the duration of response may be short, and the risk of relapse remains high, especially for those who are not eligible for Stem Cellstransplant patients. We look forward to the European Commission’s decision and, building on our commitment to providing innovative therapies that improve long-term patient outcomes, to making Onureg available to eligible patients.”

QUAZAR AML-001 Clinical Data (Click the image to view a larger version)

QUAZAR AML-001 is an international, randomized, double-blind, placebo-controlled Phase III study enrolling patients aged ≥55 years with newly diagnosed (de novo) or secondary acute myeloid leukemia (AML) and intermediate- or high-risk cytogenetics.Heredityachieved first complete remission (CR) or complete remission with incomplete hematologic recovery (CRi) after intensive induction chemotherapy. According to the investigator’s choice, patients received intensive induction chemotherapy, with or without consolidation chemotherapy, and were considered not to be hematopoietic Stem CellsCandidates for hematopoietic stem cell transplantation (HSCT).

Following intensive induction chemotherapy, 81% of patients achieved complete remission (CR), and 19% achieved complete remission with incomplete hematologic recovery (CRi). Eighty percent of patients had received at least one cycle of consolidation therapy prior to study enrollment. Subsequently, 472 patients were randomized in a 1:1 ratio to receive either Onureg 300 mg (n=238) or placebo (n=234), administered once daily for 14 days per 28-day cycle. Patients continued treatment until unacceptable toxicity or disease progression occurred.

With a median follow-up of 41.2 months, the Onureg treatment group demonstrated significant improvement in the primary endpoint of overall survival (OS) compared with the placebo group. The median OS from randomization was 24.7 months in the Onureg group versus 14.8 months in the placebo group (p=0.0009; HR=0.69 [95% CI: 0.55, 0.86]). For the key secondary endpoint of relapse-free survival (RFS), the median RFS was 10.2 months in the Onureg group compared with 4.8 months in the placebo group (p=0.0001; HR=0.65 [95% CI: 0.52, 0.81]). Regardless of cellHeredityRegardless of risk category, prior consolidation status, or CR/CRi status at enrollment, the Onureg treatment group demonstrated improvements in both OS and RFS compared with the placebo group. Compared with the placebo group, health-related quality of life (HRQoL) in the Onureg treatment group remained unchanged from baseline.

The median treatment duration with Onureg was 12 cycles (range, 1–80), compared with 6 cycles (range, 1–73) for placebo. The most common all-grade adverse events (AEs) with Onureg and placebo were nausea (65% vs 24%), vomiting (60% vs 10%), and diarrhea (50% vs 22%). The most common grade 3–4 adverse events with CC-486 and placebo were neutropenia (41% vs 24%) and thrombocytopenia (23% vs 22%), andAnemia(14% vs 13%). Serious adverse events occurred in 34% of patients in the Onureg treatment group and 25% of patients in the placebo group, primarily infections, which were reported in 17% and 8% of patients in the two groups, respectively. Treatment discontinuation due to adverse events (AEs) occurred in 13% of patients in the Onureg treatment group and 4% of patients in the placebo group. (Bioon.com)

Original Source: Bristol Myers Squibb Receives Positive CHMP Opinion for Onureg® (azacitidine tablets; CC-486) as Frontline Oral Maintenance Therapy for Adults with Acute Myeloid Leukemia in First Remission