Products

Date: 2018-07-26

Type of information: Positive opinion for the granting of a Market Authorisation in the EU

Product name: Blincyto™

Compound: blinatumomab

Therapeutic area: Cancer - Oncology

Action mechanism:

• monoclonal antibody/BiTE® antibody. Blinatumomab is an investigational BiTE® antibody designed to direct the body's cell-destroying T cells against target cells expressing CD19, a protein found on the surface of B-cell derived leukemias and lymphomas. Bispecific T cell engager (BiTE®) antibodies are a type of immunotherapy being investigated for use in fighting cancer by helping to engage the body's immune system to detect and target malignant cells. The modified antibodies are designed to engage two different targets simultaneously, thereby juxtaposing T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. BiTE antibodies help place the T cells within reach of the targeted cell, with the intent of allowing it to inject toxins and trigger the cell to die (apoptosis).

Company: Amgen (USA - CA)

Disease:

• Philadelphia -negative (Ph-) relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL)

Latest news:

• • On 26 July 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion recommending a change to the terms of the marketing authorisation for Blincyto®. The committee adopted an extension of indication as follows: Blincyto® is indicated as monotherapy for the treatment of paediatric patients aged 1 year or older with Philadelphia chromosome negative CD19 positive B-cell precursor ALL which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation.
• The full indications for Blincyto® will be as follows:
• Blincyto® is indicated as monotherapy for the treatment of adults with Philadelphia chromosome negative CD19 positive relapsed or refractory B-precursor acute lymphoblastic leukaemia (ALL).
• Blincyto® is indicated as monotherapy for the treatment of paediatric patients aged 1 year or older with Philadelphia chromosome negative CD19 positive B-cell precursor ALL which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation.
• • On November 24, 2015, Amgen announced that the European Commission (EC) has granted conditional marketing authorization for Blincyto® (blinatumomab) for the treatment of adults with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL). The conditional marketing authorization for Blincyto® is based on results of two Phase 2 studies, study '211 and '206. In the pivotal '211 trial, 42.9 percent of patients achieved complete remission (CR) or CR with partial hematological recovery (CRh*) with single-agent Blincyto®. The most serious adverse reactions that occurred during Blincyto® treatment in the pivotal '211 trial included infections, neurologic events, neutropenia/febrile neutropenia, cytokine release syndrome and tumor lysis syndrome. Study '211 evaluated Blincyto® in an open-label, multicenter, single-arm Phase 2 study. Eligible patients were at least 18 years of age with Ph- relapsed or refractory B-precursor ALL relapsed with first remission duration of less than or equal to 12 months in first salvage, or relapsed or refractory after first salvage therapy, or relapsed within 12 months of allogeneic hematopoietic stem cell transplantation (HSCT), and had at least10 percent blasts in bone marrow. The primary endpoint was the CR/CRh* rate within two cycles of Blincyto®. Of the 189 patients evaluated in the trial, 42.9 percent (81/189; 95 percent CI, 35.7 - 50.2) achieved CR or CRh* within two cycles of treatment with Blincyto® with the majority of responses (79 percent [64/81]) occurring within the first cycle of treatment. In a prespecified exploratory analysis, 82.2 percent (60/73) of minimal residual disease (MRD) evaluable patients with CR/CRh* also had an MRD response. The most common adverse reactions (greater than 20 percent) were infusion-related reactions (67.2 percent), infections (63 percent), pyrexia (59.8 percent), headache (34.4 percent), febrile neutropenia (28 percent), peripheral edema (25.9 percent), nausea (24.3 percent), hypokalemia (23.8 percent), constipation (20.6 percent) and anemia (20.1 percent). The most serious adverse reactions that occurred during BLINCYTO treatment included: infections (31.7 percent), neurologic events (16.4 percent), neutropenia/febrile neutropenia (15.3 percent), cytokine release syndrome (0.5 percent) and tumor lysis syndrome (0.5 percent). Blincyto® was granted orphan drug designation by the European Medicines Agency in 2009 for the treatment of ALL.
• • On September 24, 2015, the Committee for Medicinal Products for Human Use (CHMP) has recommended granting a conditional marketing authorisation for Blincyto® (blinatumomab) for the treatment of Philadelphia chromosome-negative acute lymphoblastic leukaemia. Conditional marketing authorisations are one of the mechanisms put in place by the Agency to facilitate market access for medicines that fulfill unmet medical needs. Blincyto® has an orphan designation.
• • On December 3, 2014, Amgen announced that the FDA has granted approval of Blincyto™ (blinatumomab) for the treatment of patients with Philadelphia chromosome-negative (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL). This indication is approved under accelerated approval. Continued approval for this indication may be contingent upon verification of clinical benefit in subsequent trials. With this approval, Blincyto™ becomes the first FDA -approved bispecific CD19-directed CD3 T-cell engager (BiTE®) antibody construct product, and the first single-agent immunotherapy to be approved for the treatment of patients with Ph- relapsed or refractory B-cell precursor ALL.
• The approval was based on the achievement of durable complete remission (CR) and response with a reduction in minimal residual disease (MRD) to less than 10-4 in a multicenter single-arm trial (Protocol MT103-211) that enrolled 185 patients with R/R ALL. Blinatumomab was administered by continuous infusion for 4 weeks of a 6-week cycle. Up to two cycles were used for induction and three cycles for consolidation. In Protocol MT103-211, 32% (95% CI, 26% - 40%) of patients with R/R ALL attained CR with 2 cycles of treatment with single-agent blinatumomab, and the response was durable (median 6.7 months; range, 0.46 - 16.5 months). Furthermore, 31% (95% CI, 25%-39%) of the patients in the study had a CR with or without complete hematological recovery but with reduction in MRD to
• Of the 185 patients evaluated in the trial, 41.6 percent (77/185; 95 percent CI: 34.4-49.1) achieved complete remission or complete remission with partial hematologic recovery (CR/CRh*) within two cycles of treatment with blinatumomab, which was the primary endpoint of the study. The majority of responses (81 percent [62/77]) occurred within the first cycle of treatment. Among patients who achieved CR/CRh*, 39 percent (30/77) went on to HSCT, and 75.3 percent (58/77 95 percent CI: 64.2-84.4) achieved minimal residual disease (MRD) response, a measure of eradication of residual disease at the molecular level.
• Safety was evaluated in 212 patients with R/R ALL treated with blinatumomab. The most common adverse reactions (greater than or equal to 20%) were pyrexia (62%), headache (36%), peripheral edema (25%), febrile neutropenia (25%), nausea (25%), hypokalemia (23%), rash (21%), tremor (20%), and constipation (20%). A neurological toxicity occurred in approximately 50% of patients and was a frequent reason for interruption of therapy.
• For patients weighing at least 45 kg, the recommended dose and schedule for blinatumomab is 9 mcg/day on days 1-7 and at 28 mcg/day on days 8-28 of the first 42-day cycle, and 28 mcg/day on days 1-28 in later cycles.
• Amgen and its subsidiary Onyx Pharmaceuticals, Inc. , which will commercialize Blincyto™ in the U.S., have announced the availability of Onyx Pharmaceuticals 360TM (Onyx 360), to patients receiving Blincyto™ in the U.S. Onyx 360 is a comprehensive patient and caregiver support and services program designed to help patients navigate the treatment journey, including reimbursement and payment support, treatment support and referrals to third-party organizations for day-to-day needs and emotional support.
• • On October 9, 2014, Amgen announced that the FDA has accepted for review the Biologics License Application (BLA) for the investigational bispecific T cell engager (BiTE®) antibody construct, blinatumomab. The BLA is for the treatment of adults with Philadelphia-negative (Ph-) relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL), a rapidly progressing cancer of the blood and bone marrow.1 As part of the acceptance, the FDA granted blinatumomab priority review with a Prescription Drug User Fee Act (PDUFA) action date of May 19, 2015. A Marketing Authorization Application (MAA) has also been submitted to the European Medicines Agency (EMA) via the centralized procedure for approval to market blinatumomab for the treatment of adults with Ph- relapsed/refractory B-precursor ALL.
• • On September 22, 2014, Amgen announced submission of a Biologics License Application (BLA) to the FDA seeking approval for its investigational bispecific T cell engager (BiTE®) antibody construct, blinatumomab. The BLA is for the treatment of adults with Philadelphia -negative (Ph-) relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). Blinatumomab, the first of the BiTE® antibody constructs, has received both orphan drug designation and breakthrough therapy designation from the FDA for the treatment of ALL. The submission includes data from a Phase 2 trial of adult patients with Ph- relapsed/refractory B-precursor ALL treated with blinatumomab, which successfully met its primary endpoint.
• • On July 1, 2014, Amgen announced that the FDA has granted Breakthrough Therapy Designation to investigational bispecific T cell engager (BiTE®) antibody blinatumomab, for adults with Philadelphia -negative (Ph-) relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL), a rapidly progressing cancer of the blood and bone marrow1. The Breakthrough Therapy Designation was based on the results of a Phase 2 trial of 189 adult patients with Ph- relapsed/refractory B-precursor ALL treated with blinatumomab. Data from the Phase 2 trial were most recently presented at the 50th Annual Meeting of the American Society of Clinical Oncology ( ASCO ) and the 19th Congress of the European Hematology Association (EHA).

Patents:

Submission of marketing authorization application USA :

Submission of marketing authorization application UE:

Withdrawal of marketing authorization application USA:

Withdrawal of marketing authorization application UE:

US authorization: 2014-12-03

UE authorization: 2015-11-23

Favourable opinion UE: 2015-09-24/2018-07-26

Favourable opinion USA:

Orphan status USA: 2008-05-16

Orphan status UE: 2009-07-24

Pediatric exclusivit _USA:

Pediatric exclusivity UE:

OTC status:

Other news:

Is general: Yes