Australia phát minh thành công thuốc làm tan chảy tế bào ung thư
Australia phát minh thành công thuốc làm tan chảy tế bào ung thư
Một loại thuốc có thể làm “tan chảy” tế bào đã được chứng nhận điều trị trên người ở Australia, Thông tấn ABC đưa tin hôm 10-1.
Được phát triển ở Melbourne, thuốc Venetoclax sẽ được bán trên thị trường với tên gọi Venclexta đã được Cục Quản lý Dược phẩm Australia (TGA) chứng nhận điều trị cho bệnh nhân mắc bệnh bạch cầu lymphocytic mãn tính.
Thuốc cũng được chứng nhận sử dụng ở Mỹ, sẽ giúp bệnh nhân không cần điều trị tiêu chuẩn hoặc bất kỳ liệu pháp nào khác.
Tiến sĩ David Huang, tác giả công trình nghiên cứu Venetoclax (Ảnh: ABC)
Venetoclax hoạt động bằng cách ngăn chặn hoạt động của protein BCL-2 cho phép tế bào ung thư sống sót, một giải pháp mà các nhà nghiên cứu trên toàn thế giới đã dày công nghiên cứu trong hơn 30 năm qua.
Doug Hilton, giám đốc Viện Nghiên cứu Y học Walter và Eliza Hall cho biết chứng nhận rất quan trọng đối với bệnh nhân có ít lựa chọn điều trị.
“Như một mũi tên độc, Venetoclax bay thẳng đến trung tâm BCL-2”, ông Hilton cho Thông tấn ABC biết.
“Thực tế người dân Australia mắc bệnh bạch cầu lymphocytic mãn tính bây giờ có thể hưởng lợi từ một loại thuốc như Venetoclax”, ông cho biết thêm.
Andrew Roberts, một giáo sư huyết học công tác tại bệnh viện Hoàng gia Melbourn cho biết thuốc cũng kết với một số phương pháp điều trị được chứng nhận để điều trị các loại bệnh ung thư máu khác.
“Nghiên cứu đang được tiến hành chỉ ra rằng thuốc này rất thích hợp để chống lại các loại bệnh ung thư khác, vì vậy, sự khởi đầu này là một bước ngoặt lớn”, ông Robert chia sẻ với ABC.
Tiến sĩ David Huang, nhà khoa học phát triển thuốc từ Viện Nghiên cứu Y học Walter và Eliza Hall đã giành giải thưởng Khoa học Eureka dành cho Phát minh Y học năm 2016.
Phạm Trúc
AbbVie’s venetoclax granted FDA Breakthrough Therapy Designation for CLL patients with 17p deletion
AbbVie (NYSE: ABBV) today announced its investigational medicine venetoclax, an inhibitor of the B-cell lymphoma-2 (BCL-2) protein that is being developed in partnership with Genentech and Roche, has been granted Breakthrough Therapy Designation by the FDA for the treatment of chronic lymphocytic leukemia (CLL) in previously treated (relapsed/refractory) patients with the 17p deletion genetic mutation.
CLL is a slow-progressing cancer of the bone marrow and blood in which the bone marrow makes too many lymphocytes, a type of white blood cell. CLL accounts for approximately one quarter of the new cases of leukemia diagnosed in the United States. Approximately 3-10 percent of CLL patients have 17p deletion at diagnosis, and it occurs in 30-50 percent of patients with relapsed/refractory CLL. The 17p deletion mutation is a genomic alteration in which a part of chromosome 17 is absent. The median life expectancy for CLL patients with 17p deletion is less than 2-3 years.
“The Breakthrough Therapy Designation of venetoclax supports the continued development of this investigational medicine in CLL patients with 17p deletion,” said Michael Severino, M.D., executive vice president of research and development and chief scientific officer, AbbVie. “The continuing advancement of the venetoclax development program is one example of AbbVie’s focus on delivering innovative medicines that address unmet clinical needs.”
According to the FDA, Breakthrough Therapy Designation is intended to expedite the development and review of drugs for serious or life-threatening conditions. The criteria for Breakthrough Therapy Designation includes preliminary clinical evidence demonstrating a drug may have substantial improvement on at least one clinically significant endpoint compared to available therapy. A Breakthrough Therapy Designation conveys all of the fast track program features, as well as more intensive FDA guidance on an efficient drug development program.
Venetoclax Gaining Ground in Two Types of Leukemia
Marina Konopleva, MD, PhD
The results of this trial of venetoclax are encouraging and warrant additional study in patients with AML.
—Marina Konopleva, MD, PhD
Venetoclax, formerly known as ABT-199, is moving forward into phase III development in acute myelogenous leukemia (AML) and chronic lymphocytic leukemia (CLL), based on encouraging data from separate phase Ib and II trials presented at the 56th Annual Meeting and Exposition of the American Society of Hematology (ASH). Venetoclax is being studied in combination with other drugs used to treat AML and CLL. It is also being studied in non-Hodgkin lymphoma.
Venetoclax is an inhibitor of the B-cell lymphoma–2 (BCL-2) protein, which interferes with cell death and is expressed in cancers of the lymph nodes, spleen, and other organs of the immune system. Venetoclax “cuts off” BCL-2, thereby restoring apoptosis of cancer cells.
Acute Myelogenous Leukemia
Encouraging results were reported from a phase II trial evaluating single-agent venetoclax in patients with relapsed/refractory AML and as front-line therapy in AML patients unfit for intensive chemotherapy.1
“AML is an aggressive cancer with low survival rates, and there is a high need for new, effective treatment options. The results of this trial of venetoclax are encouraging and warrant additional study in patients with AML,” said Marina Konopleva, MD, PhD, of The University of Texas MD Anderson Cancer Center, Houston.
The study included 32 patients. Venetoclax achieved an overall response rate of 19%; two patients had a complete response, and four patients had a complete response with incomplete platelet recovery.
Isocitrate dehydrogenase (IDH) mutations are currently of interest in AML and are thought to be a potential target in this malignancy. Three of the patients who had complete responses and incomplete platelet recovery had IDH mutations; two of the IDH-positive patients achieved minimal residual disease negativity, with complete abolishing of leukemic cells.
Venetoclax was successful in reducing the bone marrow blast count. In evaluable patients who received venetoclax, the median blast count was reduced by 36%; six patients (19%) had at least a 50% reduction in blasts.
Adverse events occurring in up to 25% of patients included nausea, diarrhea, fatigue, neutropenia, and vomiting. Grade 3 and 4 adverse events occurring in up to three patients were febrile neutropenia, anemia, and pneumonia.
Chronic Lymphocytic Leukemia
A phase Ib study of the combination of venetoclax plus rituximab (Rituxan) demonstrated encouraging safety and excellent activity in patients with CLL.2Venetoclax will move on to a phase III study, which will compare it in combination with rituximab vs bendamustine (Treanda) and rituximab in previously treated CLL.
“Venetoclax plus rituximab is highly active in relapsed/refractory CLL, achieving an overall response rate of 88% and a complete response rate of 31%. The results suggest that rituximab adds to the efficacy of venetoclax,” said lead author Andrew Roberts, MD, of Royal Melbourne Hospital, Parkville, Australia. “Seventeen patients became minimal residual disease–negative on treatment, which is impressive bone marrow clearance,” he noted.
Venetoclax as a single agent induced rapid responses in about 80% of patients with relapsed/refractory CLL. Preclinical models showed synergy between venetoclax and rituximab, one of the backbones of treatment of CLL. The phase Ib study was undertaken to determine whether the addition of rituximab would improve the efficacy of venetoclax.
The phase Ib study was designed to identify a maximal tolerated dose of venetoclax as well as the optimal schedule of giving the drug with rituximab. The study enrolled 49 patients with relapsed/refractory CLL, with a maximum of three previous myelosuppressive regimens and no previous transplant.
Treatment discontinuation was reported in 10 patients, one after the occurrence of tumor lysis syndrome. This adverse reaction led to modifications of the initial dosing regimen for venetoclax, starting at 20 mg daily and increasing in increments weekly to the recommended dose. Rituximab was given every 4 weeks for six doses. “The new schedule overcomes tumor lysis syndrome,” Dr. Roberts said.
Venetoclax was generally well tolerated, with mild gastrointestinal toxicity and grade 3 or 4 myelosuppression: neutropenia, 47%; thrombocytopenia, 16%; and anemia, 14%.
The overall response rate was 88%; 31% had a complete response or a complete response with incomplete platelet recovery; 45% had a partial response; and 12% had an unconfirmed partial response. Similar rates of responses were also seen in the subset of patients with 17p deletion.
Nine of the 15 complete responders tested negative for minimal residual disease on flow cytometry, and an additional responder tested negative for minimal residual disease at 14 months. Eight of the partial responders tested negative for minimal residual disease. None of the five complete responders who discontinued therapy had disease progression up to 26 weeks.
The study failed to identify a maximum tolerated dose; 400 mg is the currently recommended phase II dose based on toxicity and efficacy data. Higher doses were associated with slightly more neutropenia, gastrointestinal toxicity, and dose reductions. ■
Disclosure: Drs. Konopleva and Roberts have received research funding from AbbVie and Genentech. Dr. Roberts is employed by the Walter and Eliza Hall Institute of Medical Research, which receives milestone payments for the development of ABT-199.
References
1. Konopleva M, Pollyea DA, Potluri J, et al: A phase 2 study of ABT-199 in patients with acute myelogenous leukemia. 2014 ASH Annual Meeting. Abstract 118. Presented December 7, 2014.
2. Roberts AW, Ma S, Brander DM, et al: Determination of the recommended phase 2 dose of ABT-199 combined with rituximab in patients with relapsed/refractory chronic lymphocytic leukemia. 2014 ASH Annual Meeting. Abstract 325. Presented December 8, 2014.
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