19 November 2018 - - The US Food and Drug Administration has granted Breakthrough Therapy Designation to Adcetris (brentuximab vedotin) for previously untreated systemic anaplastic large cell lymphoma or other CD30-expressing peripheral T-cell lymphomas, including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with CHP (cyclophosphamide, doxorubicin, and prednisone), US-based Seattle Genetics, Inc. (NASDAQ: SGEN) said.

The positive topline results of the phase 3 ECHELON-2 clinical trial were announced in October 2018, followed by the submission of a supplemental Biologics License Application to the FDA in November 2018.

Additional data will be presented at the upcoming American Society of Hematology annual meeting, December 1-4, 2018 in San Diego, Calif.

Adcetris is an antibody-drug conjugate directed to CD30, which is expressed on the surface of several types of PTCL. Adcetris is currently not approved for the frontline treatment of PTCL.

The FDA's Breakthrough Therapy Designation is intended to expedite the development and review of promising drug candidates for serious or life-threatening conditions.

It is based upon clinical evidence of substantial improvement over existing therapies on one or more clinically significant endpoints.

This Breakthrough Therapy Designation was based on data from the phase 3 ECHELON-2 clinical trial evaluating the combination of Adcetris plus CHP versus the control arm, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), in previously untreated CD30-expressing PTCL.

The ECHELON-2 study met its primary endpoint demonstrating a statistically significant improvement in progression-free survival of Adcetris in combination with CHP versus CHOP as assessed by an Independent Review Facility (IRF; hazard ratio=0.71; p-value=0.0110).

The Adcetris plus CHP arm also demonstrated superior overall survival, a key secondary endpoint, compared to CHOP (hazard ratio=0.66; p-value=0.0244). All other key secondary endpoints, including PFS in patients with systemic anaplastic large cell lymphoma (sALCL), complete remission rate and objective response rate were statistically significant in favor of the Adcetris plus CHP arm.

The safety profile of Adcetris plus CHP in the ECHELON-2 trial was comparable to CHOP and consistent with the established safety profile of Adcetris in combination with chemotherapy.

The randomised, double-blind, placebo-controlled phase 3 trial is investigating Adcetris plus CHP (cyclophosphamide, doxorubicin, prednisone) versus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) as frontline therapy in patients with CD30-expressing peripheral T-cell lymphoma, also known as mature T-cell lymphoma.

The primary endpoint is progression-free survival per Independent Review Facility assessment, with events defined as progression, death, or receipt of chemotherapy for residual or progressive disease.

Secondary endpoints include PFS in patients with systemic anaplastic large cell lymphoma (sALCL), complete remission rate, overall survival and objective response rate, in addition to safety.

The multi-center trial was conducted at sites across North America, Europe and Asia and was designed to enroll 450 patients, approximately 75% of whom were to be diagnosed with sALCL.

The ECHELON-2 trial is being conducted under a Special Protocol Assessment agreement from the US Food and Drug Administration and the trial also received European Medicines Agency scientific advice.
Please see Important Safety Information, including Boxed Warning, at the end of this press release.

Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma.

There are more than 60 subtypes of non-Hodgkin lymphomas which are broadly divided into two major groups: B-cell lymphomas, which develop from abnormal B-lymphocytes, and T-cell lymphomas, which develop from abnormal T-lymphocytes.

There are many different forms of T-cell lymphomas, some of which are extremely rare. T-cell lymphomas can be aggressive (fast-growing) or indolent (slow-growing).

PTCL accounts for approximately 10 % of non-Hodgkin lymphoma cases in the US and Europe and may be as high as 24 % in parts of Asia.

Adcetris is being evaluated broadly in more than 70 clinical trials in CD30-expressing lymphomas.

These include the recently completed phase 3 ECHELON-2 trial in frontline peripheral T-cell lymphomas (also known as mature T-cell lymphoma), the completed phase 3 ECHELON-1 trial in previously untreated Hodgkin lymphoma, the completed phase 3 ALCANZA trial in cutaneous T-cell lymphoma, and the ongoing CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma.

Adcetris is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E, utilizing Seattle Genetics' proprietary technology.

The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells.

Adcetris injection for intravenous infusion has received FDA approval for five indications in adult patients with: (1) previously untreated Stage III or IV classical Hodgkin lymphoma, in combination with chemotherapy, (2) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (3) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (4) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (5) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides who have received prior systemic therapy.

Health Canada granted Adcetris approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-autologous stem cell transplantation consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.

Adcetris received conditional marketing authorization from the European Commission in October 2012.

The approved indications in Europe are: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (2) the treatment of adult patients with relapsed or refractory sALCL, (3) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, and (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma after at least one prior systemic therapy.

Adcetris has received marketing authorization by regulatory authorities in 72 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See select important safety information, including Boxed Warning, below.

Seattle Genetics and Takeda are jointly developing Adcetris.

Under the terms of the collaboration agreement, Seattle Genetics has US and Canadian commercialisation rights and Takeda has rights to commercialise Adcetris in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for Adcetris on a 50: 50 basis, except in Japan where Takeda is solely responsible for development costs.

Seattle Genetics, Inc. is an emerging multi-product, global biotechnology company that develops and commercializes transformative therapies targeting cancer to make a meaningful difference in people's lives. Adcetris (brentuximab vedotin) utilises the company's industry-leading antibody-drug conjugate technology and is currently approved for the treatment of multiple CD30-expressing lymphomas.

Beyond Adcetris, the company has established a pipeline of novel targeted therapies at various stages of clinical testing, including three in ongoing pivotal trials for solid tumors. Enfortumab vedotin for metastatic urothelial cancer and tisotumab vedotin for metastatic cervical cancer utilize our proprietary ADC technology.

Tucatinib, a small molecule tyrosine kinase inhibitor, is in a pivotal trial for HER2-positive metastatic breast cancer.

In addition, we are leveraging our expertise in empowered antibodies to build a portfolio of proprietary immuno-oncology agents in clinical trials targeting hematologic malignancies and solid tumors.

The company is headquartered in Bothell, Washington, and has a European office in Switzerland.