Date: 2017-07-25
Type of information: Granting of a Market Authorisation in Canada
Product name: Adcetris®
Compound: brentuximab vedotin
Therapeutic area: Cancer - Oncology
Action mechanism:
- antibody drug conjugate. Adcetris® (brentuximab vedotin) is an antibody-drug conjugate (ADC) comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE). The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalisation into CD30-expressing tumor cells. The CD30 antibody part of the product acts as a carrier for the cytotoxic substance. When the antibody attached by the linker to the cytotoxin attaches to the CTCL cells, it is taken up by the cells. Once inside the cancer cells, the linker is cut and the cytotoxic molecule, monomethyl auristatin E, gets released and stops cell division. The cancer cells are then expected to undergo programmed cell death. The anti-tumour activity of brentuximab-vedotin has been established in the HL and sALCL study populations as well as in the relapsed or refractory HL patients ineligible for ASCT/multidrug chemotherapy. The different clinical endpoints demonstrated clinical benefit in terms of disease control, resolution of B-symptoms and in terms of enabling further potentially curative treatment options.
Company: Seattle Genetics (USA - MA)
Disease:
- consolidation therapy immediately following an autologous stem cell transplant (ASCT) in CD30+ Hodgkin lymphoma (HL) patients at high risk of relapse
Latest news:
- • On July 25, 2017, Seattle Genetics announced that Health Canada has issued a non-conditional marketing authorization for use of Adcetris® as post-autologous stem cell transplant (ASCT) consolidation treatment of patients with Hodgkin lymphoma (HL) at increased risk of relapse or progression. The indication was based on positive results from the phase 3 AETHERA clinical trial.
- • On July 6, 2016, Takeda Pharmaceutical announced that the European Commission (EC) has extended the current conditional marketing authorization of Adcetris® and approved Adcetris® for the treatment of adult patients with CD30+ Hodgkin lymphoma at increased risk of relapse or progression following autologous stem cell transplant (ASCT). The decision follows a positive opinion from the Committee for Medicinal Products for Human Use on May 26, 2016. The AETHERA trial is the first completed randomized study that has explored consolidation treatment immediately following ASCT as a way of extending the effect of transplant for prevention of relapse among people with Hodgkin lymphoma. The AETHERA trial demonstrated that patients with Hodgkin lymphoma who received Adcetris® (plus best supportive care) as consolidation therapy immediately following ASCT lived significantly longer without disease progression compared to patients who received placebo (plus best supportive care) as assessed by an independent review committee (hazard ratio=0.57; p-value=0.001), which equates to a 75 percent improvement in PFS. PFS was assessed after a minimum of two years post initiation of treatment for all study patients. An updated analysis conducted after three years of follow up showed sustained PFS improvement (per independent review committee; HR=0.58; 95%CI (0.41,0.81). A pre-specified interim analysis of overall survival showed no statistically significant difference between the treatment arms.
- • On April 20, 2015, Seattle Genetics announced that the FDA has accepted for filing a supplemental Biologics License Application (BLA) for Adcetris® (brentuximab vedotin) in the AETHERA setting for the post-transplant consolidation treatment of Hodgkin lymphoma (HL) patients at high risk of relapse or progression. The FDA granted Priority Review for the application and the Prescription Drug User Fee Act (PDUFA) target action date is August 18, 2015. The submission of the supplemental BLA is based on positive results from AETHERA trial that was designed to determine if 16 cycles of Adcetris® as consolidation therapy immediately following an autologous stem cell transplant (ASCT) could extend progression-free survival (PFS) in HL patients at high risk of relapse or progression. Results from the phase 3 AETHERA trial were published in The Lancet in March 2015. Results from the AETHERA trial in 329 HL patients at high risk of relapse following ASCT included: The trial achieved its primary endpoint and demonstrated a significant increase in PFS per independent review facility, with a hazard ratio of 0.57 and a p-value of 0.001. Median PFS was 43 months for patients who received Adcetris® versus 24 months for patients who received placebo. The two-year PFS rate was 63 percent in the Adcetris® arm compared to 51 percent in the placebo arm. The PFS benefit was consistent across all pre-specified subgroups, including primary refractory patients, patients who relapsed within twelve months of frontline therapy and patients who relapsed after twelve months with extranodal disease.
- • On February 18, 2015, Seattle Genetics announced that it has submitted a supplemental Biologics License Application (BLA) to the FDA based on data from the phase 3 AETHERA trial of Adcetris® (brentuximab vedotin) as consolidation therapy immediately following an autologous stem cell transplant (ASCT) in Hodgkin lymphoma (HL) patients at high risk of relapse.
Patents:
Submission of marketing authorization application USA : 2015-02-18
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization:
UE authorization: 2016-07-06
Favourable opinion UE: 2016-05-26
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
- Seattle Genetics and Millennium are jointly developing Adcetris®. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and the Takeda Group has rights to commercialize Adcetris® in the rest of the world. Seattle Genetics and the Takeda Group are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where the Takeda Group will be solely responsible for development costs. In April 2012, Seattle Genetics and Millennium, a wholly owned subsidiary of Takeda Pharmaceutical Company have formed a collaboration with Ventana Medical Systems. Under the collaboration agreement, Ventana will seek to develop, manufacture and commercialize a molecular companion diagnostic test with the goal of identifying patients who might respond to treatment with Adcetris® based on CD30 expression levels in their tissue specimens.
Is general: Yes
