A few days ago, AbbVie (AbbVie) and Roche (Roche) co-developed blockbuster anti-cancer drug venetoclax has been granted a breakthrough therapy designation by the FDA, combined with obinutuzumab, the first-line treatment of untreated chronic lymphocytic leukemia (CLL) . This is the fifth time that venetoclax has received this certification since its listing in 2016.
In addition, the complementary new drug application (sNDA) of this combination therapy will be reviewed using the Real-Time Oncology Review (RTOR) pilot project. RTOR allows the FDA to obtain the key data of clinical trials before the formal application and start communicating with the applicant. When the application is submitted, the review team that is already familiar with the data can immediately initiate a more effective, timely and thorough review, and can make an approval decision in as little as two weeks. This means that this combination therapy is expected to be approved as a first-line therapy for CLL patients in the near future.
CLL usually occurs in the blood and bone marrow and is characterized by the gradual accumulation of excessive abnormal lymphocytes. It is one of the most common types of adult leukemia. There were approximately 20,000 new cases of CLL in the United States in 2018. Although the symptoms of CLL may disappear after treatment, cancer cells often make a comeback, making CLL patients have to undergo additional treatment for a long time. Therefore, patients need better treatments to help them prolong progression-free survival (PFS) and minimize the risk of disease recurrence.
Venetoclax is a highly selective and potent B-cell lymphoma factor-2 (BCL-2) inhibitor, and it is also the first FDA-approved therapy for BCL-2. BCL-2 plays an important role in cell apoptosis and can prevent the apoptosis of a variety of cells including lymphocytes. In certain blood cancers and other types of tumors, venetoclax, which is designed to inhibit the function of BCL-2, can restore the apoptosis process of cancer cells and realize the self-destruction of cancer cells. Obinutuzumab targets the CD20 antigen that is usually expressed on the surface of specific types of B cells. It can directly attack malignant B cells and can also exert its effects through its own immune system. Researchers believe that the combination therapy of these two blood cancer drugs has a better effect on CLL.
The sNDA submission is based on data from the Phase 3 trial CLL14. The CLL14 trial aims to evaluate the effectiveness and safety of the combination therapy of venetoclax and obinutuzumab as a first-line therapy without chemotherapy in a fixed course of 12 months compared with the combination therapy consisting of obinutuzumab and chlorambucil. According to the standard evaluation of the International Chronic Lymphocytic Leukemia Symposium (iwCLL), the combination therapy of venetoclax has reached the primary endpoint of PFS with good safety.
Dr. Mohamed Zaki, Global Head and Vice President of AbbVie Hematology Development, said: "The trial results show that the combination therapy of venetoclax and obinutuzumab, after a fixed course of administration, can prevent the deterioration of CLL and prolong the PFS of CLL patients. AbbVie I look forward to working closely with the FDA under the RTOR project to bring this combination therapy as a first-line therapy to CLL patients as soon as possible."
