Drug Name (Brand / Generic)
Adcetris® (brentuximab vedotin)
Adcetris® (brentuximab vedotin) is a treatment for relapsed or refractory (r/r) Hodgkin’s lymphoma (HL) and anaplastic large cell lymphoma (ALCL) that was developed by Seattle Genetics and Millennium Pharmaceuticals, a wholly owned subsidiary of Takeda Pharmaceutical.
A biologics licence application (BLA) for the drug was filed by Seattle Genetics in February 2011, which was accepted by the US Food and Drug Administration (FDA) in May 2011.
A six month priority review was also granted for the two indications, and the drug was approved in August 2011 for the treatment of HL and systemic anaplastic large cell lymphoma (sALCL).
Takeda and Millennium submitted a marketing authorisation application (MAA) for the drug to the European Medicines Agency (EMA), which included Phase II trial data. It was accepted in June 2011.
The EMA gave Adcetris positive opinion for conditional approval in July 2012 for the treatment of adult patients with r/r CD30 positive HL, and r/r sALCL.
The drug also obtained orphan drug designation for both r/r HL and ALCL indications in Europe.
In addition, Adcetris® was approved in Japan by the Japanese Ministry of Health, Labour and Welfare (MHLW) for the treatment of ALCL patients in January 2014, as well as granted US FDA approval for the treatment of classical HL patients at high risk of relapse or progression after autologous stem cell transplant (ASCT) in August 2015. The FDA’s approval was based on positive Phase III clinical trial Aethera.
In January 2016, the European Commission (EC) granted approval to Adcetris® to re-treat adult patients with r/r HL or sALCL that previously received and responded to Adcetris and later relapsed. Later, in June of the same year, the drug received EC approval to treat CD30-positive HL in patients at high risk of relapse or progression after ASCT.
Adcetris® received approval in Japan to treat CD30-positive frontline HL patients in combination with doxorubicin, vinblastine and dacarbazine (AVD) in September 2018. The approval was based on the positive results of Phase III trial ECHELON-1.
Adcetris® combined with CHP chemotherapy received the FDA’s approval to treat patients previously untreated with sALCL or other CD30-expressing peripheral T-cell lymphomas (PTCL) in November 2018 based on Phase III clinical trial ECHELON-2.
Lymphoma is a type of blood cancer occurring in the white blood cells. HL and Non-HL are the two types of the disease.
White blood cells are made up of T-lymphocytes (T-cells) and B-lymphocytes (B-cells), which provide immunity against bacterial infections and viruses respectively. Increased and abnormal growth in the number of lymphocytes results in lymphoma.
HL is usually observed in young people aged 15 to 35 or adults aged above 50.
Hodgkin Reed-Sternberg cells are present in the white blood cells of HL patients. These cells express a protein called CD30.
Adcetris® is an antibody-drug conjugate (ADC) consisting of the drug monomethyl auristatin E (MMAE) linked to a monoclonal antibody (mAb) anti-CD30. The ADC binds to the CD30 of Reed-Sternberg cells and forms an ADC-CD30 complex.
This complex moves towards lysosome where the MMAE is released, which causes breakdown of the microtubules resulting in the G2/M cell cycle arrest and cell death (apoptosis).
Phase I trials to evaluate the safety and efficacy of the drug on the cardiac system in patients with CD30 positive cancer were initiated in January 2010.
Phase I trials, to evaluate the safety and efficacy of the drug when used in combination with chemotherapy for treating newly diagnosed HL patients, were initiated in February 2010.
A total of 70 patients were enrolled and administered brentuximab in combination with chemotherapy with doxorubicin, bleomycin, vinblastine, dacarbazine in combination (ABVD) or brentuximab in combination with AVD. The study was completed by November 2012.
A Phase II trial was conducted to evaluate the safety and efficacy of brentuximab as a single agent in patients with r/r HL. The study was initiated in February 2009 with a primary completion achieved in August 2010.
Phase III trial called Aethera was conducted to evaluate the safety and efficacy of the drug in comparison with placebo. The randomised, double-blind, and placebo-controlled study enrolled 329 post-ASCT patients.
The patient group had high risk of residual HL following a stem cell transplant and were administered either brentuximab or placebo intravenously every 21 days during the trial.
The study was initiated in April 2010, was completed by June 2013.
Phase I trials to evaluate the safety of the brentuximab in combination with chemotherapy in ALCL patients were initiated in February 2011. The trial enrolled 52 patients and was completed by December 2012.
Another Phase II trial to evaluate the safety and efficacy of the drug as single agent in patients with ALCL enrolled 58 patients. The trial was initiated in February 2009 and had a primary completion date of August 2010. The patients were administered 1.8mg/kg of brentuximab every 21 days.
Another Phase II trial to assess the effect of brentuximab in controlling the ALCL, lymphomatoid papulosis (LyP) or mycosis fungoides (MF) was initiated in June 2011 and enrolled 35 patients, who were administered 1.8mg/kg of brentuximab a day intravenously.
Adcetris® in combination with chemotherapy was studied in a global, randomised, double-blind, multi-centre trial Phase III ECHELON-2 in previously untreated patients with CD30-expressing PTCL. Significant improvement was noticed in progression-free survival of patients receiving Adcetris® compared to those on standard of care therapy.
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