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

It's another one gone and another one gone for Amgen, as the pharmaceutical giant reported the latest clinical stoppage for a bispecific T-cell engager, or BiTE, therapy. 

Amgen has stopped enrolling acute myeloid leukemia patients in a phase 1 clinical trial of its half-life extended FLT3 BiTE therapy AMG 427. News of the stoppage comes months after Amgen hit pause on a clutch of other BiTE clinical trials.

AMG 427 was moved into a phase 1 study in 2018. Amgen last week updated the listing for the therapy to “active, not recruiting” without providing an explanation for the decision to stop enrolling new patients. The biotech shared further details in an emailed statement.

"As has been seen with other bispecifics, we have encountered cytokine release syndrome in the AMG 427 Phase 1 program and are currently working on optimizing the treatment approach, especially given the anti-leukemia activity also observed in the program.  Patient with relapsed and refractory AML have a very poor prognosis, with survival often measured in weeks or a few months.  We are working hard to resume enrollment in the attempt to develop a therapy in an area where there remains significant unmet medical need," the spokesperson said. 

Amgen moved AMG 427 into the clinic despite the availability of small molecules against the antigen FLT3, such as Novartis’ Rydapt. The company believed the therapy's targeting of both mutant and wild-type forms of the receptor may lead to better outcomes. The study that will offer early insights into whether that idea holds up in the clinic is due to wrap up in 2023, but for now has stopped working towards a target enrollment of 130 participants. 

RELATED: ESMO: Early days, but Amgen's BiTE drug in prostate cancer shows encouraging activity

The pause is the latest in a series of temporary stoppages for BiTE clinical trials. In February, Amgen revealed pauses to clinical trials of BiTE molecules against BCMA, CD33 and EGFR variant III.

Companies developing BiTEs are aiming to provide better efficacy, easier administration methods and fewer side effect compared to traditional CAR-T therapies. 

Amgen disclosed the resumption of enrollment in the study of BCMA BiTE pavurutamab during the second-quarter update. Enrollment for the multiple myeloma clinical trial was paused while the company discussed “protocol modifications to optimize safety monitoring and mitigation with the FDA.” At the time, analysts at Jefferies speculated the modifications were intended to mitigate the risk of cytokine release syndrome (CRS), which is a known inflammatory response caused by immunotherapies like BiTEs that can be fatal.

The pause occurred around the time that Amgen shared clinical data on pavurutamab, also known as AMG 701. In the update, Amgen revealed more than half of patients experienced CRS, although less than 10% had a grade 3 reaction. 

Amgen is yet to restart enrollment in the paused CD33 and EGFR variant III studies. The CD33 study is paused pending the generation of “further information on the CD33 program through progression of AMG 330.” Amgen stopped the EGFR variant III study as it prioritized its portfolio. 

RELATED: Gilead-partnered Teneobio and its next-gen cancer work snapped up by Amgen for $2.5B

The news comes days after Amgen snapped up Gilead-partnered Teneobio for $2.5 billion to complement the company's existing prostate cancer portfolio, which includes the BiTE acapatamab. The therapy showed it can stand on its own two feet in early data released in September 2020.