Type of information: Acceptation for review of a sNDA
Product name: Adcetris®
Compound: brentuximab vedotin
Therapeutic area: Cancer - Oncology
- antibody drug conjugate/monoclonal antibody. 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 - WA), a wholly owned subsidiary of Takeda Pharmaceutical (Japan)
- • On September 21, 2018, Takeda Pharmaceutical announced that it has obtained an additional indication and dosage & administration for the use of Adcetris® (brentuximab vedotin) in combination with doxorubicin, vinblastine and dacarbazine as a frontline treatment option for CD30-positive Hodgkin lymphoma patients in Japan.
- The Ministry of Health, Labour and Welfare designated Adcetris® as an orphan drug for “CD30-positive Hodgkin lymphoma and anaplastic large cell lymphoma” in March 2012.
- Takeda obtained this additional indication based on the positive results of the global Phase 3 ECHELON-1
study designed to compare Adcetris® plus AVD (doxorubicin, vinblastine, dacarbazine) to ABVD
(doxorubicin, bleomycin, vinblastine, dacarbazine) as frontline therapy in adult patients with newly
diagnosed advanced Hodgkin lymphoma. The study enrolled 1,334 patients who had histologically-confirmed diagnosis of Stage III or IV Hodgkin lymphoma and had not been previously treated with systemic chemotherapy or radiotherapy. The Data was submitted to Ministry of Health, Labour and Welfare in January 2018.
- • On January 2, 2018, Seattle Genetics announced that the FDA has accepted for filing a supplemental Biologics License Application (BLA) for Adcetris® (brentuximab vedotin) in combination with chemotherapy for the frontline treatment of patients with advanced classical Hodgkin lymphoma. The FDA granted Priority Review for the application, and the Prescription Drug User Fee Act (PDUFA) target action date is May 1, 2018.
- The submission of the supplemental BLA is based on results from the ECHELON-1 trial that was designed to determine if Adcetris® in combination with chemotherapy could extend modified progression-free survival (modified PFS) in previously untreated advanced classical Hodgkin lymphoma patients. Seattle Genetics reported the primary data from this trial in the Plenary Scientific Session of the 2017 ASH Annual Meeting with simultaneous publication in the New England Journal of Medicine. The data demonstrated superior activity of the Adcetris®-containing regimen over standard of care.
- In October 2017, the FDA granted Adcetris® Breakthrough Therapy Designation based on the ECHELON-1 study results.
- The ECHELON-1 study achieved its primary endpoint with the combination of Adcetris® plus Adriamycin, bleomycin, and vinblastine resulting in a statistically significant improvement in modified PFS versus the control arm of ABVD as assessed by an Independent Review Facility (IRF) (p-value=0.035). This corresponds to a 23 percent reduction in the risk of progression, death or need for additional anticancer therapy. Per IRF assessment, the two-year modified PFS rate for patients in the ADCETRIS plus AVD arm was 82.1 percent compared to 77.2 percent in the control arm.
Submission of marketing authorization application USA :
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
Favourable opinion UE:
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: