Amgen Announces First-In-Human Data Evaluating Investigational Novel BiTE® Immunotherapies AMG 420 And AMG 330 At ASH 2018

Phase 1 Results of Amgen's BiTE® Platform in Heavily Pre-Treated Patients With Multiple Myeloma and Acute Myeloid Leukemia

FDA Grants Fast Track Designation for AMG 420

THOUSAND OAKS, CA, USA I December 3, 2018 I Amgen (NASDAQ: AMGN) today announced the first clinical results from studies evaluating investigational novel bispecific T cell engager (BiTE®) immunotherapies AMG 420 and AMG 330. In two separate Phase 1 dose escalation studies, AMG 420, which targets B-cell maturation antigen (BCMA), and AMG 330, which targets CD33, provided early evidence of tolerability and anti-tumor activity in patients with relapsed and/or refractory multiple myeloma and relapsed or refractory acute myeloid leukemia (AML), respectively. These data were highlighted during oral presentations at the 60th American Society of Hematology (ASH) Annual Meeting & Exposition in San Diego.

BiTE® antibody construct technology, pioneered by Amgen, is an innovative treatment approach that helps the body's immune system attack cancer cells without the removal of immune cells from the patient. Amgen is studying a number of "off-the-shelf" investigational BiTE® immunotherapies, with distinct targets, across a range of hematologic and solid tumors.

"Building on our success with the only approved BiTE® immunotherapy available for patients, Amgen is emphasizing our commitment to the potential of this platform by advancing the development of approximately a dozen novel molecules across hematologic and solid tumor targets in hopes of continuing to offer meaningful advances to patients in need," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "We're encouraged by the early results of investigational BiTE® immunotherapies AMG 420 and AMG 330, especially when considered in the context of these heavily pre-treated patients, many of whom have run out of available options. We look forward to sharing more results from our BiTE® pipeline at future medical meetings."

ASH Abstract #1010: Treatment with AMG 420, an anti-B-Cell Maturation Antigen (BCMA) Bispecific T-cell Engager (BiTE®) Antibody Construct, Induces Minimal Residual Disease (MRD) Negative Complete Responses in Relapsed and/or Refractory (R/R) Multiple Myeloma (MM) Patients: Results of a First-in-Human (FIH) Phase 1 Dose Escalation Study

The data shared at ASH were the first presentation of all endpoints from this Phase 1 dose-escalation trial of AMG 420 in patients with relapsed and/or refractory multiple myeloma. The objectives of the study included assessment of safety, tolerability and anti-tumor activity of AMG 420 per International Myeloma Working Group 2006 Uniform Response Criteria for Multiple Myeloma.

In the study, 42 patients with relapsed and/or refractory multiple myeloma who had progression after at least two prior lines of treatment (including a proteasome inhibitor and an immunomodulatory imide drug) received AMG 420 at varying doses [0.2 to 800 µg/day (d)]. AMG 420 induced clinical responses in 13 patients, including complete responses (CR) in seven patients. Four patients treated at the 400 µg/d dose achieved minimal residual disease (MRD) negative complete responses, meaning that no cancer cells were detectable in the bone marrow. The objective response rate at 400 µg/d was 70 percent (seven of 10 patients), with six patients still responding up to 7.5 months. One dose-limiting toxicity was observed up to the 400 µg/d dose (peripheral polyneuropathy, which improved to baseline after intravenous immunoglobulin and corticosteroid treatment).

Of those patients with serious adverse events (AEs) (n=20, 48 percent), 17 required hospitalization and four had prolonged hospitalization. Serious AEs included infections (n=12), peripheral polyneuropathy (n=2), and one each of liver failure, cardiac failure, edema, biliary obstruction, spinal cord compression, renal failure and weight loss. Treatment-related serious AEs included polyneuropathy (n=2, both grade 3) and edema (n=1, grade 3). Cytokine release syndrome (CRS) was seen in 16 patients (grade 1, n=13; grade 2, n=2; grade 3, n=1). In this study, 800 µg/d was determined to not be tolerable, as two out of the three patients treated at this dose experienced dose-limiting toxicities.

Two patients died during the course of the study from AEs not considered treatment-related. One patient died after the first cycle of treatment from acute respiratory distress due to concurrent flu and aspergillosis. The second patient died from liver failure secondary to a viral infection during the course of treatment.

"These first-in-human data of a BCMA-targeting BiTE® immunotherapy showed encouraging evidence of AMG 420 activity, with no major toxicities up to the 400 µg/d dose in patients with relapsed and/or refractory multiple myeloma who received a median of four prior therapies," said Max S. Topp, M.D., professor, Hospital of Wuerzburg, Germany and AMG 420 clinical study investigator. "Despite recent treatment advances, multiple myeloma continues to be a disease characterized by cycles of relapse and recurrence requiring additional therapies to help control the disease."

Additionally, AMG 420 was granted Fast Track Designation by the U.S. Food and Drug Administration (FDA). Fast track is a process designed to facilitate the development, and expedite the review of drugs to treat serious conditions and fill an unmet medical need. The purpose is to get important new drugs to the patient earlier. Fast Track addresses a broad range of serious conditions.

ASH Abstract #25: A Phase 1 First-in-Human Study of AMG 330, an Anti-CD33 Bispecific T-cell Engager (BiTE®) Antibody Construct, in Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)

In a separate first-in-human Phase 1 dose escalation study, 40 patients with relapsed or refractory AML were enrolled to receive AMG 330 in 12 dose cohorts with a target dose range of 0.5 to 480 µg/d. The study objectives were to evaluate the safety, pharmacokinetics and pharmacodynamics of AMG 330 and to estimate the maximum tolerated dose. Results showed that two patients in the trial achieved a CR at the 240 µg/d dose and two patients achieved a CR with incomplete blood count recovery, one at the 240 µg/d dose and one at the 120 μg/d dose. The CRs were not sustained beyond one cycle of treatment.

Patients in the trial received a median of one (range: 1-6) cycle with AMG 330; the majority of patients discontinued treatment for disease progression.  Other reasons for study discontinuation included AEs (n=6, 2 treatment-related) and patient request (n=2).

Serious AEs were seen in 73 percent of patients (treatment-related in 17 patients). The most common serious AEs seen in more than one patient included CRS (n=11), febrile neutropenia (n=7), pneumonia (n=4), leukopenia (n=4), pyrexia (n=3), thrombocytopenia (n=3) and subdural hematoma (n=2). One patient died on study due to AML progression and one due to intracranial hemorrhage (neither treatment-related). There were dose-limiting toxicities of grade 2 CRS and grade 4 ventricular fibrillation with a target dose of 480 μg/d administered as a single-step regimen.

"The majority of adult AML patients will not be cured with standard chemotherapy, underscoring the need for innovative treatment options for those who have relapsed or are refractory to currently available treatments1," said Farhad Ravandi, M.D., Janiece and Stephen A. Lasher professor of medicine and chief of section of Developmental Therapeutics in the Department of Leukemia at the University of Texas – MD Anderson Cancer Center and AMG 330 clinical study investigator. "These early data are encouraging as they indicate AMG 330 may have anti-leukemic activity in heavily pretreated patients with relapsed or refractory AML, validating the need for continued evaluation of the BiTE® platform in targeting CD33."

About BiTE® Technology
Bispecific T cell engager (BiTE®) antibody construct is an innovative technology that can be engineered to target any tumor antigen expressed by any type of cancer. The protein molecules are designed to kill malignant cells using the patient's own immune system by bridging T cells to tumor cells. BiTE® antibody construct helps connect the T cells to the targeted cell, with the intent of causing T cells to inject toxins which trigger cancer cell death (apoptosis). Amgen is developing BiTE® antibody constructs to uniquely (or specifically) target numerous hematologic malignancies and solid tumors.

About Amgen's Commitment to Oncology
Amgen is committed to helping patients take on some of the toughest cancers, such as those that have been resistant to drugs, those that progress rapidly through the body and those where limited treatment options exist. Amgen's supportive care treatments help patients combat certain side effects of strong chemotherapy, and our targeted medicines and immunotherapies focus on more than a dozen different malignancies, ranging from blood cancers to solid tumors. With decades of experience providing therapies for cancer patients, Amgen continues to grow its portfolio of innovative and biosimilar oncology medicines.

For more information, follow us on www.twitter.com/amgenoncology.

About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.

References
1.    Bose P, Vachhani P, Cortex E. Treatment of Relapsed/Refractory Acute Myeloid Leukemia. Curr Treat Options Oncol. 2017;18(3):17.

SOURCE: Amgen

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