AbbVie, a global biopharmaceutical company, announced that the European Commission (EC) has authorised VENCLYXTO® (venetoclax) as a first-in-class, oral, once-daily medicine that selectively inhibits the function of the BCL-2 protein, restoring the body's ability to trigger cancer cell self-destruction. Venetoclax has been granted marketing authorisation as monotherapy for the treatment of chronic lymphocytic leukaemia (CLL) in adult patients in the absence of 17p deletion or TP53 mutation who have failed both chemo'''immunotherapy and a B-cell receptor (BCR) inhibitor. Venetoclax is also indicated as monotherapy for the treatment of adult CLL patients in the presence of 17p deletion or TP53 mutation who are either unsuitable for or have failed a BCR inhibitor.
Professor Peter Hillmen, Consultant Haematologist, Leeds Teaching Hospitals NHS Trust and Coordinating Investigator of the venetoclax studies in the UK said, "Venetoclax represents an important new option to offer eligible patients with CLL who have a very poor outcome with conventional therapies. Studies have shown that clinically significant numbers of patients respond to the treatment, with a number of these achieving complete responses. For clinicians, it has been meaningful to observe that some patients are achieving a deeper remission where minimal disease is not detectable on a molecular level, rarely seen in pre-treated patients. These types of clinical advances are bringing us closer than ever to successfully treating these types of cancers."
CLL is the most common form of leukaemia in adults, affecting the lives of nearly 3,500 people in the UK each year. CLL has a highly variable clinical course, with the cancer growing and progressing slowly in some people whereas in others the cancer is more aggressive and treatment is required sooner. The build-up of abnormal/immature lymphocytes compromises patients' ability to ward off infections and attacks on the immune system. Other common symptoms include swollen lymph glands, abdominal discomfort, weight loss, fever and severe fatigue which significantly impacts quality of life.
Despite treatment, the majority of people living with CLL will eventually have their disease recur. In people for whom BCR inhibitors fail, less than half will survive longer than 3 months.While for people who develop or harbor gene mutations, such as 17p deletion or TP53 mutation, treatment is particularly challenging and these are associated with poorer quality of life and a median life expectancy of less than two to three years with current standard-of-care regimens.
Nick York, from the CLL Support Association said, "We are pleased about the venetoclax marketing authorisation announcement. This may begin to address a critical unmet need in a difficult-to-treat patient population who have used all available treatment options. At the moment, there is a treatment void for those with hard to treat CLL who are not suitable for treatment with BCR inhibitors or who have relapsed from them. The evidence we have seen so far for venetoclax suggests it can help to extend lives and can potentially play a role in enabling patients, their carers and families to more fully live their lives."
"AbbVie is making significant investment in studying ways to block BCL-2 activity in cancer and with this licence we are very pleased by the opportunity to bring venetoclax to eligible UK patients who have had limited options to date. We are also continuing to investigate this treatment's first in class mode of action for application in other blood cancers where UK patients might benefit." said Alice Butler, Medical Director, AbbVie UK.
In a Phase 2, two arm study of venetoclax in 64 CLL patients who relapsed or were refractory to BCR inhibitors, the primary endpoint, overall response rate was 67 per cent. Twenty-five per cent of patients achieved minimal residual disease (MRD) negativity in the peripheral blood, including 1 in the bone marrow. MRD was an exploratory endpoint and is defined as <1 CLL cell per 104 leukocytes in the sample. At 12 months, 72% per cent of patients were yet to have their disease progress. In a separate Phase 2, single arm study in 107 relapsed/refractory CLL patients with 17p deletion, the primary endpoint, overall response rate was 79 per cent, with 7 per cent in complete remission. In an exploratory endpoint evaluated by investigator assessment, minimal residual disease (MRD) negativity in peripheral blood was achieved in 27.1 per cent (41/158) of patients, including 15 patients who were also MRD negative in the bone marrow Investigator-assessed median progression free survival was 27.2 months.
The most commonly occurring adverse reactions (≥20%) of any grade in patients receiving venetoclax in clinical trials were neutropenia/neutrophil count decreased, diarrhoea, nausea, anaemia, upper respiratory tract infection, fatigue, hyperphosphataemia, vomiting, and constipation. The most frequently reported serious adverse reactions (≥2%) were pneumonia, febrile neutropenia, and tumour lysis syndrome.
Full summary of product characteristics is available at www.medicines.org.uk/emc