Micromet, Inc. outlined a clinical development plan intended to support US registration of its lead product candidate blinatumomab in patients with B-precursor relapsed/refractory (r/r) acute lymphoblastic leukaemia (ALL). The plan incorporates advice received from the US Food and Drug Administration (US FDA) within the context of a Type C meeting.
“Recent feedback received from the US FDA provides a roadmap to blinatumomab registration in a patient population with limited therapeutic options,” said Christian Itin, PhD, Micromet's president and chief executive officer. “We look forward to initiating later this quarter the first of two planned clinical trials collectively intended to support a biologics license application for full approval.”
Later this quarter, the Company plans to initiate a single-arm phase II clinical study that will enroll approximately 65 adult patients with B-precursor r/r ALL. Patients will receive blinatumomab for up to five treatment cycles. Each cycle will consist of 28 days of treatment followed by two weeks off therapy. The primary endpoint of the study is complete remission (CR) and complete remission with only partial recovery of blood counts (CRh). Secondary endpoints include duration of CR and CRh* and overall survival. The study will be conducted at leading cancer centers in the US and EU.
“In the event that initial results generated from the global phase II trial are compelling, we plan to discuss with the US FDA potential avenues to accelerate blinatumomab's path to market.” said Jan Fagerberg, MD, PhD, Micromet's senior vice president and chief medical officer.
The Company also reviewed with the US FDA the preliminary design of a planned randomized, controlled, phase III clinical study intended to evaluate the efficacy and safety of blinatumomab in comparison to chemotherapy in adult patients with r/r B-precursor ALL. Efficacy will be assessed based on blinatumomab's effect on a time dependent endpoint. The study will be conducted at leading cancer centres in the US and in Europe. Data from this trial, if positive, are intended to support full approval of blinatumomab in this patient population.
The Company recently received clearance from the US FDA to conduct a phase I/II clinical study in paediatric and adolescent patients with r/r ALL. This will be an open label two-part study, conducted in collaboration with the Children's Oncology Group and International BFM study group. The first part is designed to determine the appropriate dose and schedule of blinatumomab according to patient age group. Once the recommended dose and schedule is determined, additional patients will be enrolled in the second part of the study to further assess the safety and antitumor activity of blinatumomab. The Company expects to enroll approximately 80 patients at leading investigative sites in the US, Canada and EU. Data from this trial will inform the Company's registration strategy in this patient population.
Interim results from a phase II trial presented at the 2011 Meeting of the European Haematology Association show that blinatumomab produced a high CR rate in adult patients with ALL who had relapsed following treatment with standard therapy. 75% of patients (9 of 12) achieved a CR or CRh following treatment with blinatumomab1. All nine responding patients achieved a complete molecular response, or had no evidence of leukemic cells in their bone marrow, a key prognostic factor for patient survival. Notably, four patients with genetic abnormalities typically associated with poorer outcomes all achieved a CR or CRh. The most common clinical adverse events were fever, peripheral edema and fatigue. Treatment of two of the twelve patients was interrupted due to fully reversible and manageable central nervous system (CNS) events.
Blinatumomab (MT103) is a next-generation monoclonal antibody designed to direct the body's cell destroying T-cells against CD19, a protein expressed on the surface of B-cell derived ALL and non Hodgkin's lymphomas (NHL).
Micromet has received orphan drug designation from the European Medicines Agency for blinatumomab for the treatment of ALL, mantle cell lymphoma and chronic lymphatic leukaemia (CLL) and from the US FDA for the treatment of ALL, CLL and indolent B cell lymphoma.
ALL is an aggressive cancer of the blood and bone marrow that afflicts 5,330 patients in the US annually. Patients with ALL have abnormal white blood cells (lymphocytes) that crowd out healthy white and red blood cells and platelets, leading to infection, anaemia (fatigue), easy bleeding and other serious effects. Current treatment for Philadelphia negative R/R ALL consists of combinations of toxic chemotherapy drugs that in the majority of cases fail to drive the disease into remission. In more than 30 years, no new drug has been approved for use in this setting, leaving physicians with few options to improve long-term patient outcomes other than variations in the dose and schedule of old drugs with limited efficacy. With current approaches, complete remission rates typically range from 20 – 30 %. Standard chemotherapy is associated with a mortality rate of up to 23 %. The average five-year survival rate for adult ALL patients after first relapse is 7%.
Micromet is a biopharmaceutical company focused on the discovery, development and commercialization of innovative antibody-based therapies for the treatment of cancer.