- The company announced that it has aligned with collaborator Takeda Pharmaceutical Company Limited (Takeda), as well as with the U.S. Food and Drug Administration (FDA) and European Union regulators, on a protocol amendment to unblind the phase 3 AETHERA clinical trial in the second half of 2014.
- Under the collaboration with Takeda, ADCETRIS recently received marketing authorization in Australia and Singapore, and regulatory approvals are being pursued in multiple other countries globally during 2014, including Japan.
- ADCETRIS was recently added to the National Comprehensive Cancer Network (NCCN) guidelines for the treatment of relapsed CD30-positive peripheral T-cell lymphoma (PTCL).
- Seattle Genetics reviewed anticipated 2014 data presentations and program milestones from its portfolio of ADC programs, including a broad clinical development program evaluating ADCETRIS for the treatment of CD30-positive malignancies and progress with ADC candidates SGN-CD19A, SGN-CD33A and SGN-CD70A.
ADCETRIS 2014 MilestonesADCETRIS is being evaluated in more than 30 ongoing clinical trials, including four phase 3 trials, designed to establish it as the foundation of therapy for CD30-positive malignancies. The phase 3 AETHERA trial is evaluating ADCETRIS versus placebo for the treatment of patients at high risk of residual HL following autologous stem cell transplant (ASCT) to determine if ADCETRIS can extend progression-free survival in a consolidation or maintenance-type setting for these post-ASCT HL patients. Based on current estimates of progression events from pooled, blinded data from the ongoing trial, the study has been amended to enable a time point-driven progression-free survival analysis after patients have completed all required scans, which is anticipated to occur in the second half of 2014. The AETHERA trial is not being conducted under a Special Protocol Assessment (SPA) agreement from the FDA and has not been designated as a confirmatory trial to convert either accelerated approval or conditional marketing authorization to regular approval. This trial will provide drug safety data analyses that fulfill one of the company’s FDA post-approval requirements. In addition, data presentations from several ongoing ADCETRIS studies are expected at medical forums in 2014, including data from:
- a phase 1/2 study in combination with bendamustine in second-line HL;
- clinical trials in relapsed B-cell non-Hodgkin lymphoma, including DLBCL; and
- follow-up from a phase 2 trial in frontline HL patients age 60 and above.
ADC Pipeline Program 2014 MilestonesSeattle Genetics has a robust pipeline of ADC programs in ongoing clinical trials, including SGN-CD19A, SGN-CD33A, SGN-LIV1A, ASG-22ME and ASG-15ME. SGN-CD19A is an ADC targeting CD19, a protein expressed uniformly on most B-cell malignancies, which is being evaluated in phase 1 clinical trials for the treatment of ALL and non-Hodgkin lymphoma. Data presented at the 55 th American Society of Hematology (ASH) Annual Meeting in December 2013 demonstrated encouraging early antitumor activity and a generally well-tolerated safety profile among heavily pretreated patients with ALL. In addition, multiple complete remissions have been observed in a parallel phase 1 study evaluating SGN-CD19A in aggressive non-Hodgkin lymphoma. Additional data from both ongoing phase 1 clinical trials are expected to be presented in 2014. SGN-CD33A is a novel CD33-directed ADC utilizing Seattle Genetics’ next generation technology. The CD33 antibody is attached to a highly potent cytotoxic agent called a pyrrolobenzodiazepine (PBD) dimer via a proprietary site-specific conjugate technology to a monoclonal antibody with engineered cysteines (EC-mAb). SGN-CD33A is being evaluated in a phase 1 clinical trial for patients with AML. The first presentation of clinical data from SGN-CD33A is expected during 2014. Seattle Genetics is also advancing SGN-LIV1A, ASG-22ME and ASG-15ME in ongoing phase 1 clinical trials for a variety of solid tumor types. The company also plans to advance SGN-CD70A, a novel CD70-directed ADC utilizing its proprietary PBD dimer and EC-mAb technologies, into phase 1 clinical trials during 2014. SGN-CD70A will be the company’s sixth ADC pipeline program currently in clinical evaluation. About ADCs Antibody-drug conjugates (ADCs) are monoclonal antibodies that are designed to selectively deliver cytotoxic agents to tumor cells. This approach is intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy while enhancing antitumor activity. ADCETRIS is an ADC directed to CD30, a defining marker of classical HL and known to be expressed in some types of non-Hodgkin lymphoma.
About ADCETRISADCETRIS (brentuximab vedotin) is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), 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 for intravenous injection received accelerated approval from the FDA and approval with conditions from Health Canada for two indications: (1) the treatment of patients with HL after failure of ASCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates, and (2) the treatment of patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen. The indications for ADCETRIS are based on response rate. There are no data available demonstrating improvement in patient-reported outcomes or survival with ADCETRIS. ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive HL following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. ADCETRIS has received marketing authorization by regulatory authorities in more than 35 countries. See important safety information below. Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize 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 will be solely responsible for development costs. About Seattle Genetics Seattle Genetics is a biotechnology company focused on the development and commercialization of innovative antibody-based therapies for the treatment of cancer. Seattle Genetics is leading the field in developing antibody-drug conjugates (ADCs), a technology designed to harness the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. The company’s lead product, ADCETRIS ® (brentuximab vedotin) is an ADC that, in collaboration with Takeda Pharmaceutical Company Limited, has been approved for two indications in more than 35 countries, including the U.S., Canada and members of the European Union. Additionally, ADCETRIS is being evaluated broadly in more than 30 ongoing clinical trials. Seattle Genetics is also advancing a robust pipeline of clinical-stage ADC programs, including SGN-CD19A, SGN-CD33A, SGN-LIV1A, ASG-22ME and ASG-15ME. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including AbbVie, Agensys (an affiliate of Astellas), Bayer, Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com. ADCETRIS (brentuximab vedotin) U.S. Important Safety Information BOXED WARNING Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS. Contraindication: Concomitant use of ADCETRIS and bleomycin is contraindicated due to pulmonary toxicity.
Warnings and Precautions:
- Peripheral neuropathy: ADCETRIS treatment causes a peripheral neuropathy that is predominantly sensory. Cases of peripheral motor neuropathy have also been reported. ADCETRIS-induced peripheral neuropathy is cumulative. Monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness and institute dose modifications accordingly.
- Infusion reactions: Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an infusion reaction occurs, interrupt the infusion. If anaphylaxis occurs, immediately and permanently discontinue the infusion.
- Hematologic toxicities: Grade 3 or 4 anemia, thrombocytopenia and prolonged (≥1 week) severe neutropenia can occur with ADCETRIS. Febrile neutropenia has been reported with ADCETRIS. Monitor complete blood counts prior to each dose of ADCETRIS and consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. Closely monitor patients for fever. If Grade 3 or 4 neutropenia develops, manage by G-CSF support, dose delays, reductions or discontinuation.
- Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia and sepsis/septic shock (including fatal outcomes) have been reported in patients treated with ADCETRIS. Closely monitor patients during treatment for the emergence of possible bacterial, fungal or viral infections.
- Tumor lysis syndrome: Closely monitor patients with rapidly proliferating tumor and high tumor burden.
- Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death has been reported in ADCETRIS-treated patients. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider the diagnosis of PML in any patient presenting with new-onset signs and symptoms of central nervous system abnormalities. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture or brain biopsy. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
- Stevens-Johnson syndrome (SJS): SJS has been reported with ADCETRIS. If SJS occurs, discontinue ADCETRIS and administer appropriate medical therapy.
- Embryo-fetal toxicity: Fetal harm can occur. Advise pregnant women of the potential hazard to the fetus.
Drug Interactions:Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to MMAE. Use in Specific Populations: MMAE exposure is increased in patients with hepatic impairment and severe renal impairment. For additional important safety information, including Boxed WARNING, please see the full U.S. prescribing information for ADCETRIS at www.seattlegenetics.com or www.ADCETRIS.com . Certain of the statements made in this press release are forward looking, such as those, among others, relating to therapeutic potential of ADCETRIS, SGN-CD19A, SGN-CD33A, SGN-LIV1A, ASG-22ME, ASG-15ME and SGN-CD70A. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the inability to show sufficient activity in the AETHERA trial necessary for approval and the risk of adverse events as ADCETRIS, SGN-CD19A, SGN-CD33A, SGN-LIV1A, ASG-22ME, ASG-15ME and SGN-CD70A advance in clinical trials. In addition, data from our clinical trials, including our pivotal trials which were the basis for FDA accelerated approval, may not necessarily be indicative of subsequent clinical trial results. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company’s 10-Q for the quarter ended September 30, 2013 filed with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise.