Date: 2017-08-16
Type of information: Submission of an sNDA
Product name: Adcetris®
Compound: brentuximab vedotin
Therapeutic area: Cancer - Oncology - Rare diseases
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.
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.
Company: Takeda Global Research and Development Centre (UK), subsidiary of Takeda Pharmaceutical (Japan) Seattle Genetics (USA - WA)
Disease:
- cutaneous T-cell lymphoma (CTCL)
- CD30-expressing mycosis fungoides (MF)
- primary cutaneous anaplastic large cell lymphoma (pcALCL)
Latest news:
- • On August 16, 2017, Seattle Genetics announced that the FDA has accepted for filing a supplemental Biologics License Application (BLA) based on data from the phase 3 ALCANZA trial and two phase 2 investigator-sponsored trials of Adcetris® (brentuximab vedotin) in patients with cutaneous T-cell lymphoma. The FDA granted Priority Review for the application and the Prescription Drug User Fee Act (PDUFA) target action date is December 16, 2017. Based on discussions with the FDA, additional data from two investigator-sponsored phase 2 trials have also been incorporated into the supplemental BLA to support the potential for a broader label in CTCL.
- • On June 20, 2017, Seattle Genetics announced that it has submitted a supplemental Biologics License Application (BLA) to the FDA based on data from the phase 3 ALCANZA trial and two phase 2 investigator-sponsored trials of Adcetris® (brentuximab vedotin) in patients with cutaneous T-cell lymphoma. The supplemental BLA is primarily based on positive results from the phase 3 trial called ALCANZA that were presented at the 58th American Society of Hematology (ASH) annual meeting in December 2016 and published in the Lancet in June 2017.
- • On November 10, 2016, Seattle Genetics announced that the FDA has granted Breakthrough Therapy Designation to Adcetris® (brentuximab vedotin) for the treatment of patients with CD30-expressing mycosis fungoides and primary cutaneous anaplastic large cell lymphoma who require systemic therapy and have received one prior systemic therapy. These diseases are the most common subtypes of cutaneous T-cell lymphoma, accounting for more than 75 percent of the disease.
- This Breakthrough Therapy Designation was based on data from the phase 3 ALCANZA study. This study evaluated Adcetris® in CD30-expressing CTCL and met its primary endpoint, demonstrating a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4). This randomized trial, which received a Special Protocol Assessment (SPA) agreement from the FDA and scientific advice from the European Medicines Agency, compared the use of single-agent Adcetris® to a control arm of investigator’s choice of standard therapies, methotrexate or bexarotene, in 131 patients with CD30-expressing CTCL who received prior systemic or radiation therapy. Seattle Genetics intends to submit a supplemental Biologics License Application to the FDA in the first half of 2017 for approval in this setting.
Patents:
Submission of marketing authorization application USA : 2017-06-20
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization:
UE authorization:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE: 2012-01-11 (Takeda)
Pediatric exclusivit _USA:
Pediatric exclusivity UE:
OTC status:
Other news:
Is general: Yes