BOTHELL, Wash. & NORTHBROOK, Ill. – Oct. 7, 2016 – Seattle Genetics, Inc. (NASDAQ: SGEN) and Agensys, an affiliate of Astellas, today presented updated clinical data for enfortumab vedotin (ASG-22ME) and ASG-15ME at the European Society for Medical Oncology (ESMO) Congress being held Oct. 7-11, 2016 in Copenhagen, Denmark. Enfortumab vedotin and ASG-15ME are investigational antibody-drug conjugates (ADCs) that target the cell surface proteins Nectin-4 and SLITRK6, respectively. The clinical data for both agents continue to demonstrate overall response rates in patients with previously treated metastatic urothelial cancer, including those treated with prior checkpoint inhibitors. Safety and recommended phase 2 doses were also presented for both programs. While both phase 1 studies will continue to enroll patients, the companies plan to advance enfortumab vedotin and discuss next steps with regulatory agencies. Evaluation of next developmental steps for ASG-15ME is ongoing.
"We are pleased to advance the enfortumab vedotin development program for patients with metastatic urothelial cancer. These patients are in dire need of new treatment options as their prognosis is grim, with a five-year survival rate of about 15 percent," said Jonathan Drachman, M.D., chief medical officer and executive vice president, Research and Development at Seattle Genetics. "The antitumor activity and safety profile of enfortumab vedotin in heavily pretreated metastatic patients is encouraging, particularly in those patients who have failed both platinum-based chemotherapy and checkpoint inhibitors. We look forward to discussions with regulatory agencies."
"Both enfortumab vedotin and ASG-15ME hold potential promise for metastatic urothelial cancer patients," said Steven Benner, M.D., senior vice president, therapeutic area head for oncology development, Astellas. "As we consider our next steps in these two development programs, we also pause to thank the patients, caregivers and clinical investigators who participate in these clinical trials for the important role they play in advancing the science of cancer care."
Interim data from two phase 1 dose-escalation studies of enfortumab vedotin and ASG-15ME monotherapy in patients with metastatic urothelial cancer will be presented at the ESMO Congress during poster sessions on Sunday, Oct. 9, 2016.
The respective clinical trial data showed that each agent had antitumor activity in patients previously treated with platinum-based chemotherapy, checkpoint inhibitors, taxanes and those with liver metastases. Enfortumab vedotin and ASG-15ME were generally well-tolerated, and phase 1 enrollment is ongoing with both agents, with an increased focus on checkpoint-inhibitor treated patients to further understand safety and activity in this population. Detailed findings are summarized below:
Interim Analysis of a Phase 1 Dose Escalation Trial of ASG-22CE (ASG-22ME; enfortumab vedotin), an Antibody-Drug Conjugate (ADC) in Patients (Pts) with Metastatic Urothelial Cancer (mUC) (Abstract #788P, poster presentation on Sunday, October 9, 2016)
Data were reported from 58 patients with metastatic urothelial cancer having a median age of 67 years. Of these patients, 56 patients (97 percent) had undergone treatment with a platinum-based chemotherapy regimen and 20 patients (35 percent) had progressed on or after treatment with checkpoint inhibitors. Thirty-six patients (62 percent) had received two or more prior systemic therapies. The primary endpoints of the ongoing clinical trial are to evaluate pharmacokinetics and safety of enfortumab vedotin as a monotherapy at escalating doses of 0.5 to 1.25 milligrams per kilogram (mg/kg) weekly for three of every four week cycles. In addition, the trial is evaluating antitumor activity, objective response rate and disease control rate. Key findings include:
- Of the 49 patients evaluable for response, 18 patients (37 percent) had an objective response, including one patient (two percent) who achieved a complete response and 17 patients (35 percent) who achieved a partial response. The preliminary estimate of median progression-free survival is 16.6 weeks.
- The recommended phase 2 dose is 1.25 mg/kg. In 17 patients treated at the 1.25 mg/kg dose level, 10 patients (59 percent) had a partial response. Disease control was achieved for 14 patients (82 percent), defined as achieving complete response, partial response or stable disease.
- In the 16 patients across dose levels who had previously been treated with checkpoint inhibitors, six patients (38 percent) achieved a partial response. At the recommended phase 2 dose, four out of seven patients (57 percent) previously treated with checkpoint inhibitors achieved a partial response.
- In the 12 patients whose cancer had metastasized to the liver, five patients (42 percent) achieved an objective response. Of 20 patients previously treated with taxanes, eight (40 percent) achieved an objective response.
- The most common treatment related adverse events of any grade occurring in 20 percent or more of patients were pruritis (31 percent), fatigue (30 percent), diarrhea (29 percent), nausea (28 percent), rash (26 percent) and alopecia (21 percent).
- Eight of 19 patients (42 percent) experienced a rash at the recommended phase 2 dose and none of these patients required dose modification or discontinued therapy as a result.
- Enrollment is ongoing at 1.25 mg/kg and the study has been amended to include a checkpoint inhibitor-treated cohort to further understand safety and activity in this population.
Interim Analysis of a Phase 1 Dose Escalation Trial of the Antibody-Drug Conjugate (ADC) AGS15E (ASG-15ME) in Patients (Pts) with Metastatic Urothelial Cancer (mUC) (Abstract #780PD, poster presentation with discussion on Sunday, October 9, 2016)
Data were reported from 54 patients with metastatic urothelial cancer having a median age of 64 years. Of these patients, 52 patients (96 percent) had previously undergone treatment with a platinum-based chemotherapy regimen and 17 patients (32 percent) had progressed on or after treatment with checkpoint inhibitors. Thirty patients (56 percent) had received two or more prior systemic therapies. The primary endpoints of the ongoing clinical trial are to evaluate the pharmacokinetics and safety of ASG-15ME as a monotherapy at escalating doses of 0.1 to 1.25 mg/kg weekly for three of every four week cycles. In addition, the trial is evaluating antitumor activity, objective response rate and disease control rate. Key findings include:
- Of the 48 patients evaluable for response, 18 patients (38 percent) had an objective response, including one patient (two percent) who achieved a complete response and 17 patients (35 percent) who achieved a partial response. The preliminary estimate of median progression-free survival is 16.1 weeks.
- The recommended phase 2 dose is 1.0 mg/kg. In 20 patients treated at the 1.0 mg/kg dose level, 10 patients (50 percent) had an objective response, including one patient (five percent) who achieved a complete response and nine patients (45 percent) who achieved a partial response. Disease control was achieved for 14 patients (70 percent), defined as achieving complete response, partial response or stable disease.
- Of the 14 patients across dose levels who had previously been treated with checkpoint inhibitors, six patients (43 percent) achieved a partial response. At the recommended phase 2 dose, three out of seven patients (43 percent) previously treated with checkpoint inhibitors achieved a partial response.
- In the 13 patients whose cancer had metastasized to the liver, six patients (46 percent) achieved an objective response. Of 22 patients previously treated with taxanes, nine (41 percent) achieved an objective response.
- The most common treatment related adverse events of any grade occurring in 20 percent or more of patients were fatigue (44 percent), nausea (22 percent) and decreased appetite (20 percent).
- Fourteen patients (26 percent) experienced ocular adverse events and six patients (11 percent) developed ocular symptoms with corneal abnormalities at the recommended phase 2 dose. All events resolved with appropriate management.
- Enrollment is ongoing at 1.0 mg/kg and the study has been amended to include a checkpoint inhibitor-treated cohort to further understand safety and activity in this population.
More information about these clinical trials, including enrolling centers, is available by visiting www.clinicaltrials.gov.
About Urothelial Cancer
Urothelial cancers include carcinomas of the bladder, ureter, and renal pelvis, which occur at a ratio of 50:3:1, respectively. Most bladder cancers start in the innermost lining of the bladder, which is called the urothelium or transitional epithelium. Urothelial cancer begins when urothelial cells in the urinary bladder, ureter, or renal pelvis start to grow uncontrollably.
While patients with early stage urothelial cancer are treated with curative intent, outcomes are poor for patients diagnosed with locally advanced or metastatic disease. For the approximately 10 percent of patients with urothelial cancer whose initial diagnoses occur when they have metastatic disease, the average five-year survival is approximately 15 percent. According to the American Cancer Society, in 2016 approximately 77,000 people will be diagnosed and more than 16,000 will die from urothelial bladder cancer.
About Enfortumab Vedotin and ASG-15ME
Enfortumab vedotin is an investigational ADC composed of an anti-Nectin-4 monoclonal antibody attached to a microtubule-disrupting agent, MMAE, using Seattle Genetics proprietary, industry-leading linker technology. Enfortumab vedotin is the first and only agent to target Nectin-4, a cell adhesion molecule identified as an ADC target by Agensys (now Astellas), which is expressed on many solid tumors. Preclinical data demonstrate that enfortumab vedotin effectively binds to target cells, internalizes and induces cell-killing activity.
ASG-15ME is an investigational antibody-drug conjugate (ADC) composed of an anti-SLITRK6 monoclonal antibody attached to a microtubule-disrupting agent, monomethyl auristatin E (MMAE), using Seattle Genetics proprietary, industry-leading linker technology. ASG-15ME is the first and only agent to target SLITRK6, a transmembrane protein identified as an ADC target by Agensys, which is expressed on many solid tumors. Preclinical data demonstrate that ASG-15ME effectively binds to target cells, internalizes and induces cell-killing activity.
Nectin-4 and SLITRK6 are highly expressed in urothelial cancers, particularly bladder cancer. Enfortumab vedotin and ASG-15ME consist of monoclonal antibodies which selectively target and kill tumor cells with microtubule-disrupting agents. This approach is intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy while enhancing antitumor activity.
About Seattle Genetics
Seattle Genetics is an innovative biotechnology company that develops and commercializes novel antibody-based therapies for the treatment of cancer. The company’s industry-leading antibody-drug conjugate (ADC) technology harnesses the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. ADCETRIS® (brentuximab vedotin), the company’s lead product, in collaboration with Takeda Pharmaceutical Company Limited, is the first in a new class of ADCs commercially available globally in 65 countries for relapsed classical Hodgkin lymphoma (HL) and relapsed systemic anaplastic large cell lymphoma (sALCL). Seattle Genetics is also advancing vadastuximab talirine (SGN-CD33A; 33A), an ADC in a phase 3 trial for acute myeloid leukemia. Headquartered in Bothell, Washington, Seattle Genetics is also advancing a robust pipeline of innovative therapies for blood-related cancers and solid tumors designed to address significant unmet medical needs and improve treatment outcomes for patients. The company has collaborations for its proprietary ADC technology with a number of companies including AbbVie, Astellas, Bayer, Celldex, Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com
Astellas Pharma Inc., based in Tokyo, Japan, is a company dedicated to improving the health of people around the world through the provision of innovative and reliable pharmaceutical products. We focus on Urology, Oncology, Immunology, Nephrology and Neuroscience as prioritized therapeutic areas while advancing new therapeutic areas and discovery research leveraging new technologies/modalities. We are also creating new value by combining internal capabilities and external expertise in the medical/healthcare business. Astellas is on the forefront of healthcare change to turn innovative science into value for patients. For more information, please visit our website at www.astellas.com/en.
About the Astellas and Seattle Genetics Collaboration
Agensys (an affiliate of Astellas) and Seattle Genetics entered into the ADC collaboration in January 2007 and expanded it in November 2009. Under the collaboration, the companies are co-developing and have options to globally co-commercialize ASG-15ME and enfortumab vedotin.
Forward Looking Statements for Seattle Genetics
Certain of the statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of enfortumab vedotin and ASG-15ME their possible safety and efficacy and anticipated development activities including future clinical trials. 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 clinical trials and risk of adverse events as enfortumab vedotin and ASG-15ME advance in clinical trials even after promising results in earlier clinical trials. In addition, as our drug candidates or those of our collaborators advance in clinical trials, adverse events and/or regulatory actions may occur which affect the future development of those drug candidates and possibly other compounds using similar technology. More information about the risks and uncertainties faced by Seattle Genetics is contained under the caption “Risk Factors” included in the company’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2016 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.
Astellas Forward-Looking Statement
In this press release, statements made with respect to current plans, estimates, strategies and beliefs and other statements that are not historical facts are forward-looking statements about the future performance of Astellas. These statements are based on management’s current assumptions and beliefs in light of the information currently available to it and involve known and unknown risks and uncertainties. A number of factors could cause actual results to differ materially from those discussed in the forward-looking statements. Such factors include, but are not limited to: (i) changes in general economic conditions and in laws and regulations, relating to pharmaceutical markets, (ii) currency exchange rate fluctuations, (iii) delays in new product launches, (iv) the inability of Astellas to market existing and new products effectively, (v) the inability of Astellas to continue to effectively research and develop products accepted by customers in highly competitive markets, and (vi) infringements of Astellas’ intellectual property rights by third parties.
Information about pharmaceutical products (including products currently in development) which is included in this press release is not intended to constitute an advertisement or medical advice.
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