publication date: Dec. 9, 2016
Drugs and Targets
Avastin Plus Chemo Gets FDA Approval for a Type of Ovarian Cancer
AVASTIN (bevacizumab) received FDA approval to be used either in combination with carboplatin and paclitaxel or in combination with carboplatin and gemcitabine chemotherapy, followed by Avastin alone, for the treatment of patients with platinum-sensitive recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer.
Women are said to have a ‘platinum-sensitive’ form of the disease if a relapse occurs six months or longer following the last treatment with a platinum-based chemotherapy.
“With today’s approval of Avastin plus chemotherapy, women in the U.S. with recurrent, platinum-sensitive ovarian cancer now have a treatment option that showed a survival difference of more than five months compared to chemotherapy alone in a clinical trial,” said Sandra Horning, chief medical officer and head of Global Product Development. “This approval was based in part on a Gynecologic Oncology Group cooperative clinical trial and reinforces the importance of partnerships with study groups to identify new treatment options for people in need.”
Avastin in combination with chemotherapy for platinum-sensitive recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer was granted priority review, and today’s approval is based on results from two randomized, controlled phase III studies, GOG-0213 and OCEANS.
The GOG-0213 study demonstrated that adding Avastin to chemotherapy showed an overall survival difference of five months compared to chemotherapy alone (median OS: 42.6 months vs. 37.3 months; Hazard Ratio (HR)=0.84, 95% CI: 0.69-1.01 and HR=0.82, 95% CI: 0.68-0.996, depending on stratification factor). Both the GOG-0213 and OCEANS studies demonstrated a significant improvement in the time women lived without their disease getting worse (progression-free survival, PFS).
The GOG-0213 study showed that women lived a median of 3.4 months longer without disease progression with the addition of Avastin to chemotherapy compared to chemotherapy alone (median PFS: 13.8 months vs. 10.4 months; HR=0.61, 95% CI: 0.51-0.72). The OCEANS study showed that Avastin in combination with chemotherapy significantly improved PFS compared to placebo plus chemotherapy (median PFS: 12.4 months vs. 8.4 months; HR=0.46, 95% CI: 0.37-0.58; p<0.0001).
Overall survival, one of the secondary endpoints in the OCEANS study, was not significantly improved with the addition of Avastin to chemotherapy (HR=0.95, 95% CI: 0.77-1.17). Adverse events in both studies were consistent with those seen in previous trials of Avastin across tumor types for approved indications, but also included fatigue, low white blood cell count with fever, low sodium level in the blood, pain in extremity, low platelet count, too much protein in the urine, high blood pressure and headache.
In November 2014, Avastin received an FDA approval for the treatment of women with platinum-resistant recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer in combination with paclitaxel, pegylated liposomal doxorubicin or topotecan chemotherapy. Women are considered to have a ‘platinum-resistant’ form of the disease if a relapse occurs less than six months after the last treatment with a platinum-based chemotherapy.
ABBVIE said the European Commission granted conditional marketing authorization for Venclyxto (venetoclax) monotherapy for the treatment of chronic lymphocytic leukaemia in the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor; and for the treatment of CLL in the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.
The EC approved Venclyxto as a first-in-class, oral, once-daily medicine that selectively inhibits the function of the BCL-2 protein. BCL-2 prevents the natural death of cells, including CLL cells.
Venclyxto is being developed by AbbVie and Genentech, a member of the Roche Group. It is jointly commercialized by the companies in the U.S. and by AbbVie outside of the U.S.
The 17p deletion, a genomic alteration in which a part of chromosome 17 is absent, is found in 3 to 10 percent of previously untreated CLL cases and up to 30 to 50 percent of relapsed or refractory CLL cases. A TP53 mutation occurs in 8 to 15 percent of patients at first-line treatment and up to 35 to 50 percent of cases in refractory CLL. Those with the 17p deletion or TP53 mutations often have a particularly poor prognosis and a median life expectancy of less than two to three years with current standard-of-care regimens.
Conditional marketing authorization is granted to medicines that address an unmet medical need, where the benefit of its immediate availability to patients outweighs the risk of limited data availability, and where comprehensive data will be provided.
In April 2016, FDA granted accelerated approval of Venclexta (venetoclax) tablets for the treatment of patients with CLL with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy.
The FDA approved this indication under accelerated approval based on overall response rate, and continued approval may be contingent upon verification and description of clinical benefit in a confirmatory trial.
AMGEN and Allergan plc submitted a Marketing Authorization Application to the European Medicines Agency for ABP 215, a biosimilar candidate to Avastin (bevacizumab).
The companies said they this submission is the first bevacizumab biosimilar application submitted to the EMA.
ABP 215 is a biosimilar candidate to bevacizumab, a recombinant immunoglobulin G1 monoclonal antibody that binds to vascular endothelial growth factor and inhibits the interaction of VEGF with its receptors, VEGF receptor-1 and VEGF receptor-2, thus inhibiting establishment of new blood vessels necessary for the maintenance and growth of solid tumors.
The MAA submission includes analytical, pharmacokinetic and clinical data, as well as pharmacology and toxicology data. The phase III comparative efficacy, safety and immunogenicity study was conducted in adult patients with non-squamous non-small cell lung cancer. The phase III study confirmed no clinically meaningful difference to bevacizumab in terms of efficacy, safety and immunogenicity.
In December 2011, Amgen and Allergan plc. (then Watson Pharmaceuticals, Inc.) formed a collaboration to develop and commercialize, on a worldwide basis, four oncology antibody biosimilar medicines. Under the terms of the agreement, Amgen will assume primary responsibility for developing, manufacturing and initially commercializing the oncology antibody products.
NOVOGENE, a commercial provider of genomic services, AITbiotech Pte Ltd, a Singapore biotechnology company, and the Genome Institute of Singapore announced that NovogeneAIT Genomics Singapore–a new joint venture between Novogene and AITbiotech–will establish a joint whole genome sequencing center at Biopolis, Singapore.
The new center will provide Illumina HiSeq X based whole genome sequencing and bioinformatics analysis of human, plant and animal samples for biomedical and agricultural researchers. The center will devote a major portion of its sequencing capability to support public research projects and empower super scale sequencing initiatives in Singapore and the region.
In addition, NovogeneAIT will collaborate with GIS to develop new applications of next-generation sequencing, such as WGS solutions for cancer diagnosis and stratified cancer treatment.