Takeda’s CD30-Targeted ADC Adcetris Approved by EU as First-Line Therapy for Systemic Anaplastic Large Cell Lymphoma

May 15, 2020 /BioValleyBIOON/ -- Takeda Pharmaceutical Company Limited (Takeda Pharma) recently announced that the European Commission (EC) has approved an expansion of the conditional marketing authorization for Adcetris (brentuximab vedotin), to include: first-line treatment in combination with the CHP chemotherapy regimen (cyclophosphamide + doxorubicin + prednisone).TumorAdult patients with systemic anaplastic large cell lymphoma (sALCL) expressing CD30 (CD30-positive). This approval applies to all EU member states, Norway, Liechtenstein, and Iceland.

Notably, Adcetris is the first and only targeted therapy approved for the first-line treatment of systemic anaplastic large cell lymphoma (sALCL) in decades. Adcetris is a CD30-directed antibody-drug conjugate (ADC); CD30 is expressed on the surface of cells in various peripheral T-cell lymphomas (PTCL), including sALCL, a subtype of PTCL.

For a long time, the clinical outcomes of patients with sALCL have been poor, and many patients have not achieved the standard of care for long-term survival or remission. Clinical data show that compared to the standard treatment CHOP group, patients in the Adcetris+CHP regimen group achieved impressive clinical results while maintaining comparable safety. For previously untreated sALCL patients, the Adcetris+CHP regimen will provide a much-needed first-line treatment option.

This approval is based on data from the Phase III ECHELON-2 study. This is the largest randomized, double-blind Phase III study conducted to date in patients with peripheral T-cell lymphoma (PTCL), enrolling previously untreated CD30-positive PTCL patients (with a target proportion of systemic anaplastic large cell lymphoma [sALCL] of 75% ± 5%). The study evaluated the efficacy and safety of Adcetris in combination with the CHP chemotherapy regimen (cyclophosphamide, doxorubicin, and prednisone) as first-line treatment, compared with CHOP (cyclophosphamide, doxorubicin [an anthracycline], vincristine, and prednisone), the currently accepted standard of care for first-line treatment of PTCL. The primary endpoint was progression-free survival (PFS) as assessed by an independent review facility (IRF).

The results showed that the study met its primary endpoint: in the intent-to-treat (ITT) population, as assessed by the Independent Review Facility (IRF), the Adcetris+CHP regimen demonstrated a statistically significant improvement in progression-free survival (PFS) compared with the CHOP regimen (median PFS: 48.2 months [95% CI: 35.2–NE] vs. 20.8 months [95% CI: 12.7–47.6]; IRF-assessed hazard ratio [HR]=0.71 [95% CI: 0.54–0.93], p=0.0110).

Furthermore, compared with the CHOP regimen, the Adcetris+CHP regimen demonstrated a statistically significant improvement in the key secondary endpoint of overall survival (OS) (HR=0.66, p=0.0244), with the median OS not yet reached in either group. The Adcetris+CHP regimen also showed statistically significant advantages in other key secondary endpoints, including progression-free survival (PFS) in patients with systemic anaplastic large cell lymphoma (sALCL), complete response rate (CRR: 68% vs. 56%, p=0.007), and objective response rate (ORR: 83% vs. 72%, p=0.003).

In this study, the Adcetris+CHP regimen demonstrated comparable safety to the CHOP regimen and was consistent with the established safety profile of Adcetris in combination with chemotherapy.

Takeda Pharmaceutical GlobalTumorTeresa Bitetti, President of the Business Unit, stated, “The European Commission’s approval of Adcetris for first-line treatment of sALCL represents a significant milestone for patients diagnosed with this devastating disease. Adcetris is the first and only targeted therapy approved in decades for the first-line treatment of sALCL. Takeda remains steadfastly committed to providing life-changing treatments for cancer patients worldwide, and we are pleased to have the opportunity to bring this new option to the lymphoma community in Europe.”

Adcetris is an antibody-drug conjugate (ADC) composed of a monoclonal antibody targeting the CD30 protein and a microtubule-disrupting agent (monomethyl auristatin E, MMAE), linked via a protease-sensitive linker. This conjugation technology was developed by SeattleHereditythe company’s proprietary technology. CD30 protein is a well-established biomarker for classical Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL), while Auristatin E impedes cell division by inhibiting tubulin polymerization. Adcetris remains stable in the bloodstream and, upon binding to CD30-positiveTumorFollowing cellular internalization, MMAE is released.

Adcetris by SeattleHeredityDeveloped by Seattle Genetics, Takeda entered into a licensing agreement in 2009 to secure commercialization rights for the drug in all countries worldwide except the United States and Canada. To date, Adcetris has been approved in more than 70 countries globally for the treatment of relapsed or refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (sALCL). In the United States and the European Union, Adcetris has been approved for six adult indications.

Currently, Takeda and SeattleHeredityTakeda is actively advancing a large-scale Phase III clinical development program aimed at establishing Adcetris as a cornerstone therapy for CD30-positive lymphomas and redefining first-line clinical treatment for lymphoma. (Bioon.com)

Original source: European Commissionapproves ADCETRIS® (brentuximab vedotin) for Treatment of Adult Patients with Previously Untreated Systemic Anaplastic Large Cell Lymphoma