Date: 2016-11-10
Type of information: Clinical research agreement
Compound: Kyprolis® (carfilzomib) and Darzalex® (daratumumab)
Company: Amgen (USA - CA) Janssen Biotech, a J&J company (USA - NJ)
Therapeutic area: Cancer - Oncology
Type agreement: clinical research
Action mechanism: proteasome inhibitor/monoclonal antibody. Carfilzomib belongs to the class of proteasome inhibitors. Proteasome inhibitors block the proteasome, a system in cells that breaks down proteins when they are no longer needed. When proteins in the cancer cells are not broken down by the proteasome, the cells eventually die, slowing down the growth of the cancer. Carfilzomib is the first irreversible, highly-selective, proteasome inhibitor for multiple myeloma. The irreversible binding to the targeted proteasome leads to a more sustained inhibition with minimal inhibition of other non-targeted enzymes. Daratumumab is a human CD38 monoclonal antibody with broad-spectrum killing activity. Daratumumab is in clinical development for multiple myeloma. It targets the CD38 molecule which is highly expressed on the surface of multiple myeloma cells and may also have potential in other cancers on which CD38 is expressed, including diffuse large B-cell lymphoma, chronic lymphocytic leukemia, acute lymphoblastic leukemia, plasma cell leukemia, acute myeloid leukemia, follicular lymphoma and mantle cell lymphoma. In May, 2013, daratumumab has been granted Breakthrough Therapy Designation from the FDA for the treatment of patients with multiple myeloma who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or who are double refractory to a PI and an IMiD. In August 2012, Genmab granted Janssen Biotech, an exclusive worldwide license to develop, manufacture and commercialize daratumumab.
Disease: multiple myeloma
Details: * On November 10, 2016, Amgen announced a collaboration with Janssen Biotech, Inc. to evaluate the combination of Amgen's Kyprolis® (carfilzomib) and Janssen's Darzalex® (daratumumab) in multiple clinical studies in patients with multiple myeloma. Under the terms of the agreement, the companies may elect to supply drug only or supply drug and share development costs on a study-by-study basis. The proposed study design is a Phase 3, open-label, randomized study in multiple myeloma patients with one, two or three prior lines of therapy. Patients will be treated to progression. In the first arm, patients will receive Kyprolis® twice weekly at 56 mg/m2 and dexamethasone in combination with v (KdD). In the second arm (control), patients will receive Kyprolis® twice weekly at 56 mg/m2 and dexamethasone (Kd). The primary endpoint is progression-free survival (PFS) and the key secondary endpoints are overall response rate, minimal residual disease and overall survival.
The first study initiated as part of this agreement is a Phase 3 registrational trial evaluating Kyprolis® in combination with Darzalex® and dexamethasone compared to Kyprolis® and dexamethasone alone in patients with multiple myeloma who have had one, two or three prior lines of therapy. The rationale for combining these agents is that they have demonstrated substantial activity in multiple myeloma, with distinct and complementary mechanisms of action. The study is anticipated to start enrolling patients in April 2017 .
As part of an earlier and separate agreement, Amgen is also supplying Kyprolis® for Janssen's open-label Phase 1b study. The combination of Darzalex® and Kyprolis® is being investigated in this Phase 1b study in two cohorts. One cohort includes Darzalex® in combination with v and dexamethasone in patients who previously received one to three prior lines of therapy. The second cohort includes Darzalex® in combination with Kyprolis®, Revlimid® (lenalidomide) and dexamethasone in subjects with newly diagnosed multiple myeloma, regardless of transplantation eligibility. Both Phase 1 cohorts are fully enrolled.
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