BOTHELL, Wash.--(BUSINESS WIRE)--Seattle Genetics, Inc. (NASDAQ:SGEN) today announced several ADCETRIS (brentuximab vedotin) data presentations at the 13th International Conference on Malignant Lymphoma (ICML) being held June 17 to 19, 2015, in Lugano, Switzerland. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed in classical Hodgkin lymphoma (HL), systemic anaplastic large cell lymphoma (sALCL) and several other types of non-Hodgkin lymphoma (NHL). Seven oral presentations and one poster at ICML demonstrate the breadth of the clinical development program for ADCETRIS. Data include an additional analysis of the phase 3 AETHERA clinical trial showing that up to 16 cycles (approximately one year) of ADCETRIS consolidation therapy following autologous stem cell transplant (ASCT) significantly extended progression-free survival (PFS) versus placebo for those patients with primary-refractory HL. In addition, data from several corporate and investigator-sponsored trials with ADCETRIS showed activity in a variety of HL and NHL treatment settings. ADCETRIS is currently approved by the U.S. Food and Drug Administration (FDA) for relapsed HL and sALCL and was granted conditional marketing authorization by the European Commission for relapsed or refractory HL and sALCL.
“Since the initial FDA approval of ADCETRIS in 2011 for the treatment of relapsed HL and sALCL, it has been approved in more than 55 countries, and our clinical development program has expanded to include more than 30 corporate and investigator-sponsored clinical trials in CD30-expressing malignancies,” said Clay B. Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “The ADCETRIS data presented at ICML support our broad development plans for ADCETRIS. In the near-term, we anticipate an FDA decision on its use in the AETHERA setting as a post-transplant consolidation therapy, and, ultimately, our goal is to move even earlier into the treatment paradigm and redefine frontline treatment of HL with the addition of ADCETRIS.”
Analysis of primary-refractory Hodgkin lymphoma patients in a randomized, placebo-controlled study of brentuximab vedotin consolidation after autologous stem cell transplant (Seattle Genetics and Takeda; Abstract #120, oral presentation Friday, June 19, 2015, at 11:50 a.m. CEST)
Data were reported from an additional analysis of the phase 3 AETHERA clinical trial evaluating PFS by investigator in patients who were refractory to frontline treatment. Previously published data suggest primary-refractory HL patients have poor outcomes following ASCT, as demonstrated by the historical two-year PFS and three-year overall survival rates of less than 40 percent and 50 percent, respectively. Of the 329 patients enrolled in the AETHERA trial, 60 percent (196 patients) were primary-refractory to frontline treatment.
Results of the analysis demonstrated:
- Two-year PFS rates per investigator among primary-refractory patients on the ADCETRIS and placebo arms were 60 percent and 42 percent, respectively, consistent with the primary analysis in the full intent-to-treat population.
- Subgroup analyses of patients by disease characteristics as well as number of risk factors showed that PFS was improved broadly across subgroups, including patients with B-symptoms, extranodal involvement and those who received more than two systemic anticancer treatments pre-ASCT.
- Adverse events in primary-refractory patients who received ADCETRIS were consistent with the known safety profile.
Additional AETHERA data were included in a poster presentation reporting the frequency of healthcare resource utilization (HRU) among patients on the two treatment arms of the trial. Preliminary reports suggest a trend toward lower HRU in patients treated with ADCETRIS compared with placebo.
ADCETRIS is currently not approved for use in the AETHERA treatment setting. Based on the positive results from the AETHERA trial, a supplemental Biologics License Application (BLA) for ADCETRIS in the post-ASCT consolidation treatment of HL patients at high risk of relapse or progression was accepted for filing by the FDA. The FDA granted Priority Review for the application and the Prescription Drug User Fee Act (PDUFA) target action date is August 18, 2015.
Additional ADCETRIS corporate and investigator presentations are included below and full abstracts can be found in the ICML Educational and Abstract Book accessed on the ICML website at www.lymphcon.ch.
Wednesday, June 17, 2015
- Healthcare utilization in the AETHERA trial: phase 3 study of brentuximab vedotin in patients at increased risk of residual Hodgkin lymphoma post ASCT (Seattle Genetics and Takeda; Abstract #177, poster presentation)
Thursday, June 18, 2015
- Brentuximab vedotin plus AVD for non-bulky limited stage classical Hodgkin lymphoma: A phase 2 trial (Investigator-sponsored; Abstract #087, oral presentation at 5:15 p.m. CEST)
- Preliminary efficacy and safety of brentuximab vedotin and AVD chemotherapy followed by involved-site radiotherapy in early stage, unfavorable risk Hodgkin lymphoma (Investigator-sponsored; Abstract #088, oral presentation at 5:25 p.m. CEST)
- Sequential brentuximab vedotin and AVD for older Hodgkin lymphoma patients: Initial results from a phase 2 multicenter study (Investigator-sponsored; Abstract #089, oral presentation at 5:35 p.m. CEST)
- A phase 1 study of brentuximab vedotin (Bv) and bendamustine (B) in patients with relapsed or refractory Hodgkin lymphoma (HL) and anaplastic large T-Cell lymphoma (ALCL) (Investigator-sponsored; Abstract #090, oral presentation at 5:45 p.m. CEST)
- Brentuximab vedotin demonstrates antitumor activity in CD30+ DLBCL (Seattle Genetics; Abstract #091, oral presentation at 5:55 p.m. CEST)
- Updated results of a phase 2 trial of brentuximab vedotin combined with RCHOP in frontline treatment of pts with high-intermediate/high-risk DLBCL (Seattle Genetics; Abstract #092, oral presentation at 6:05 p.m. CEST)
ADCETRIS is not currently approved for use in frontline HL, in combination with bendamustine for relapsed or refractory HL and sALCL, or in DLBCL.
ADCETRIS is being evaluated broadly in more than 30 ongoing clinical trials, including four phase 3 studies, in earlier lines of its approved HL and sALCL indications as well as in many additional types of CD30-positive malignancies, including cutaneous T-cell lymphoma, B-cell lymphomas and mature T-cell lymphomas.
ADCETRIS (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 approved under accelerated approval based on overall response rate. An improvement in patient-reported outcomes or survival has not been established. Continued approval for these indications may be contingent upon verification and description of clinical benefit in confirmatory trials.
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 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 55 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 a CD30-targeted ADC that, in collaboration with Takeda Pharmaceutical Company Limited, is commercially available for two indications in more than 55 countries, including the U.S., Canada, Japan and members of the European Union. Additionally, ADCETRIS is being evaluated broadly in more than 30 ongoing clinical trials in CD30-expressing malignancies. Seattle Genetics is also advancing a robust pipeline of clinical-stage programs, including SGN-CD19A, SGN-CD33A, SGN-LIV1A, SGN-CD70A, ASG-22ME, ASG-15ME and SEA-CD40. 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
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS.
ADCETRIS is contraindicated with concomitant bleomycin due to pulmonary toxicity (e.g., interstitial infiltration and/or inflammation).
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.
- Anaphylaxis and infusion reactions: Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an infusion-related reaction occurs, interrupt the infusion and institute appropriate medical management. If anaphylaxis occurs, immediately and permanently discontinue the infusion and administer appropriate medical therapy.
- Hematologic toxicities: Prolonged (≥1 week) severe neutropenia and Grade 3 or 4 thrombocytopenia or anemia 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. Monitor patients for fever. If Grade 3 or 4 neutropenia develops, consider dose delays, reductions, discontinuation, or G-CSF prophylaxis with subsequent doses.
- Serious infections and opportunistic infections: Infections such as pneumonia, bacteremia and sepsis or 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.
- Increased toxicity in the presence of severe renal impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with severe renal impairment compared to patients with normal renal function. Avoid the use of ADCETRIS in patients with severe renal impairment.
- Increased toxicity in the presence of moderate or severe hepatic impairment: The frequency of ≥Grade 3 adverse reactions and deaths was greater in patients with moderate or severe hepatic impairment compared to patients with normal hepatic function. Avoid the use of ADCETRIS in patients with moderate or severe hepatic impairment.
- Hepatotoxicity: Serious cases of hepatotoxicity, including fatal outcomes, have occurred with ADCETRIS. Cases were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, and occurred after the first dose of ADCETRIS or rechallenge. Preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may also increase the risk. Monitor liver enzymes and bilirubin. Patients experiencing new, worsening, or recurrent hepatotoxicity may require a delay, change in dose, or discontinuation of ADCETRIS.
- 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. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
- Pulmonary Toxicity: Pulmonary toxicity has been reported with ADCETRIS. A causal association with single-agent ADCETRIS has not been established. In the event of new or worsening pulmonary symptoms (e.g., cough, dyspnea), perform a prompt diagnostic evaluation and institute appropriate medical therapy.
- Serious dermatologic reactions: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), including fatal outcomes, have been reported with ADCETRIS. If SJS or TEN 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.
ADCETRIS was studied as monotherapy in 160 patients in two phase 2 trials. Across both trials, the most common adverse reactions (≥20%), regardless of causality, were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.
Concomitant use of strong CYP3A4 inhibitors or inducers, or P-gp inhibitors, has the potential to affect the exposure to monomethyl auristatin E (MMAE).
Use in Specific Populations:
MMAE exposure and adverse reactions are increased in patients with moderate or severe hepatic impairment or severe renal impairment. Avoid use.
For additional Important Safety Information, including Boxed WARNING, please see the full Prescribing Information for ADCETRIS at www.seattlegenetics.com.
Certain of the statements made in this press release are forward looking, such as those, among others, relating to the potential approval by the FDA of ADCETRIS for post-ASCT consolidation treatment of HL patients at high risk of relapse or progression, future development activities including clinical trials, and the data from such trials and the therapeutic potential of ADCETRIS. 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 risk of adverse events as ADCETRIS advances in clinical trials, unexpected clinical trial results and regulatory action. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company’s 10-Q for the quarter ended March 31, 2015, 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.