Sean E. Harper, MD
A supplemental biologics license application (sBLA) has actually been submitted to the FDA to extend the approval of blinatumomab (Blincyto) to consist of the therapy of pediatric and adolescent patients along with Philadelphia chromosome-adverse (Ph-) relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
The sBLA is based about data from a single-arm phase 1/2 trial, referred to as study 205, in which blinatumomab induced finish remissions (CR) in a “clinically meaningful lot of pediatric patients along with relapsed/refractory ALL,” according to Amgen, the manufacturer of the anti-CD19 immunotherapy.
“Youngsters along with relapsed or refractory Every one of have actually pretty inadequate long term outcomes and currently there are restricted readily available treatments to induce remission,” said Sean E. Harper, MD, executive vice president of Study and Improvement at Amgen. “We anticipate collaborating along with regulatory authorities to make Blincyto readily available to this ultra-orphan patient population along with a higher unmet medical need.”
Study 205 is a multicenter, dose-finding, efficacy trial that accrued patients aged <18 years along with Ph- B-cell precursor Every one of that was refractory, had relapsed a minimum of twice, or relapsed after an allogeneic HSCT. Every one of patients in the trial have actually completed therapy and are being observed for long term outcomes. The data will certainly be submitted for publication, Amgen reported.
The a lot of common major side events (AEs) included pyrexia, febrile neutropenia, cytokine launch syndrome, sepsis, device-related infection, overdose, convulsion, respiratory failure, hypoxia, pneumonia, and multiorgan failure. These major AEs were comparable to those previously reported for blinatumomab.
The FDA granted blinatumomab an accelerated approval in this establishing in December 2014, based about phase II data demonstrating solid clinical task along with the agent in adult patients along with ALL.
In the pivotal phase II study, the CR fee was 32.4% (95% CI, 25.7-39.7), the CR along with partial hematological recovery (CRh) fee was 9.2% (95% CI, 5.4-14.3), and the combined CR/CRh fee was 41.6% (95% CI, 34.4-49.1). Overall, 80% of patients that accomplished a CR likewise responded by minimum residual ailment (MRD) testing. Roughly 39% of patients that accomplished a CR/CRh went about to obtain an HSCT.
The a lot of common all-grade AEs were pyrexia (62%), problem (36%), peripheral edema (25%), febrile neutropenia (25%), nausea (25%), hypokalemia (23%), rash (21%), tremor (20%), and constipation (20%). In all, 3 patients endured treatment-related grade 5 AEs: sepsis (n = 2) and candida infection (n = 1).
Neurological adverse effects ensued in Roughly 50% of patients. Additionally, 11% endured cytokine launch syndrome. To handle these adverse effects, the FDA approved blinatumomab along with a Boxed Warning and Risk Evaluation and Mitigation Technique (REMS).
In February, Amgen reported that the confirmatory phase III TOWER study was halted after an independent panel inspired that blinatumomab improved Total survival (OS) versus standard chemotherapy in patients along with Ph- relapsed/refractory B-cell precursor ALL.
The open-label phase III TOWER trial randomized patients in a 2:1 ratio to blinatumomab or investigator’s selection of 1 of 4 standard chemotherapy regimens. The primary endpoint was OS. Secondary endpoints included CR, duration of CR, patients attaining remission along with MRD, and safety. The data from TOWER will certainly be presented at an upcoming scientific meeting, Amgen reported.
Blinatumomab is a recombinant, single-chain monoclonal antibody that possesses antigen-recognition internet sites for CD3 and CD19. The CD3 complex features T cell surface glycoproteins, while CD19 is a tumor-associated antigen. The combination of these recognition internet sites in to 1 therapy is believed to promote cytotoxic T lymphocyte and helper T lymphocyte task versus CD19-expressing B lymphocytes.
