Amgen Halts Patient Enrollment in Phase 1 Trial of BiTE Therapy AMG 427

Compiled and Translated | Tom Li

According to the latest news, Amgen has halted patient enrollment for the clinical trial of AMG427, a bispecific T-cell engager (BiTE) therapy.

According to data updated by Amgen last week on the ClinicalTrials.gov website, the trial status is listed as "Active, not recruiting"; however, Amgen has not provided an explanation for its decision to halt the recruitment of new patients. Currently, Amgen has stopped enrolling new patients with acute myeloid leukemia in its Phase 1 clinical trial of AMG 427, a half-life extended BiTE therapy targeting the FLT3 antigen. Previously, Amgen had already paused a series of other BiTE clinical trials.

AMG427 entered Phase I clinical trials in 2018. Although small-molecule therapies targeting the FLT3 antigen (such as Novartis's Rydapt) are already available on the market, Amgen ultimately advanced AMG427 into clinical trials. The company believes that this therapy may yield improved therapeutic outcomes against both mutant and wild-type receptors. The trial is scheduled to conclude in 2023; however, Amgen has currently halted efforts to meet its original enrollment target of 130 participants.

Notably, AMG427 is only one of a series of BiTE clinical trial suspensions. In February this year, clinical development for three BiTE therapies (AMG 701, AMG 673, and AMG 596) was suspended. AMG 701 is a BCMA/CD3-targeted BiTE candidate and a follow-on to AMG 420, featuring a longer half-life. Due to safety concerns, enrollment in its Phase 1 clinical trial has been suspended. AMG 673 is a CD33/CD3-targeted BiTE candidate intended for the treatment of acute myeloid leukemia (AML). Given the more favorable profile of a comparable agent, AMG 330, Amgen suspended the clinical trial for AMG 673. Additionally, the Phase 1 clinical trial for AMG 596, an EGFR vIII/CD3-targeted BiTE candidate developed for glioblastoma, was also halted by Amgen.

Amgen’s Bispecific T-cell Engager (BiTE) therapy has consistently been a focal point of industry attention. Currently, immunotherapies targeting the BCMA antigen are primarily categorized into three major classes: Chimeric Antigen Receptor T-cell (CAR-T) therapy, represented by Celgene, bluebird bio, and Novartis; Bispecific Antibody (BsAb) therapy, represented by Amgen; and Antibody-Drug Conjugate (ADC) therapy, represented by GlaxoSmithKline. Compared with traditional CAR-T therapy, the advantages of BiTE therapy may lie in superior efficacy, simpler administration methods, and fewer side effects.

During the second-quarter update, Amgen also disclosed that it had resumed patient enrollment for the AMG701 (pavurutamab) trial. The company had previously paused enrollment in its multiple myeloma clinical trial to discuss with the FDA "optimizing safety monitoring and modifying mitigation protocols." At the time, Jefferies analysts speculated that these modifications were aimed at reducing the risk of cytokine release syndrome (CRS) in trial participants. CRS is a common side effect of immunotherapies such as BiTEs and can be fatal. Trial data revealed that over half of the patients experienced CRS, with fewer than 10% experiencing Grade 3 reactions.

Currently, Amgen has not yet resumed enrollment for its previously paused CD33 and EGFR trials. The suspension of the CD33 study is to await clinical progress on AMG 330, thereby obtaining more information regarding the CD33 program. Amgen halted the EGFR study due to other higher-priority portfolio assets. To further enhance the development capabilities of its existing BiTE antibodies, Amgen announced in late July the acquisition of TeneoBio for $2.5 billion, aiming to integrate TeneoBio’s proprietary bispecific and multispecific antibody technologies, its fully human heavy-chain antibody platform, and other related technologies. TeneoBio’s innovative T-cell engager bispecific antibody platform will serve as a complement to Amgen’s existing BiTE platform, helping the company maintain its leadership position in the T-cell engager field.

Source: Another one BiTEs the dust as Amgen pauses enrollment for phase 1 bispecific trial