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Amgen’s BCMA drug on course to challenge CAR-Ts in myeloma

BiTE will rival therapies from Bluebird, Celgene/Juno, J&J/Legend biotech

Amgen has its first data on bispecific antibody AMG 420, one of a swathe of BCMA-targeting therapies with new data at the ASH 2018 congress in multiple myeloma.

The early read-out from the phase 1 programme shows that Amgen’s anti-BCMA drug – one of its bispecific T cell engager (BiTE) immunotherapies – is holding up well in a busy field at first glance, although it remains to be seen whether it will challenge other emerging therapies, and particularly CAR-T candidates from Bluebird Bio, Celgene/Juno and Johnson & Johnson/Legend Biotech.

AMG 420 achieved an objective response in seven of 10 patients (70%) at the optimal dose tested (400µg/day),  including four complete responses with no evidence of minimal residual disease (MRD), and three complete responses with MRD, with six patients still responding up to 7.5 months. Analysts at Jefferies say the data keep Amgen “in the game” when it comes to BCMA.

A higher dose (800µg/day) proved too hard to tolerate, and one patient was unable to continue on the optimal dose because of side effects – peripheral neurotoxicity – which responded to treatment after ANG 420 was discontinued. One specialist cited by analysts at William Blair has predicted that neurotoxicity could prove to be a differentiating factor between BCMA-targeted therapies for myeloma.

There were signs of efficacy with AMG 420 even at a lower dose of 200µg/day, but the big question now is whether off-the-shelf drugs will match CAR-Ts like Bluebird’s bb2121 and bb21217 for efficacy.

Amgen drug modalities

Amgen's BiTE technology is just one of the drug modalities it is investigating Image: Amgen

In its favour is that AMG 420 is an off-the-shelf therapy, sidestepping the process of harvesting, modifying and re-infusing cells needed with CAR-T, although it’s worth mentioning that AMG 420 does require lengthy stays in the clinic to deliver the continuous infusions – four weeks out of every six-week treatment cycle. A follow-up candidate called AMG 701 has a longer half-life and could make its administration easier and is in a phase 1 trial.

Jefferies notes it is too early to call on efficacy right now, as patients enrolled onto the AMG 420 trial had an average of four prior lines of therapy, while those treated in trials of Bluebird’s CAR-Ts had seven or more, with a might higher proportion of the latter group also failing on Johnson & Johnson’s fast-growing myeloma therapy Darzalex (daratumumab).

Amgen also revealed that it has fast-track status for AMG 420 from the FDA, and intends to accelerate enrolment into an expanded study population that will include patients in earlier lines of therapy.

Amgen also reported data at ASH on another BiTE candidate called AMG 330 which targets CD33, the same target as Regeneron’s REGN1979 which posted results in lymphoma earlier during the congress.

In a 40-patient study involving patients with acute myeloid leukaemia who had undergone several prior lines of treatment, AMG 330 achieved complete responses in two patients, plus two complete responses with incomplete blood count recovery, that were however not sustained beyond one cycle of treatment.

Amgen said that the results nevertheless show evidence of anti-leukaemic activity and suggest that CD33-targeting BiTE drugs may have a role to play in heavily pre-treated AML patients. The company also has an advantage in that its technology has been proven via Blincyto, the first BiTE-based therapy, approved in 2017.

David Reese

"Building on our success with the only approved BiTE immunotherapy available for patients, Amgen is emphasising our commitment to the potential of this platform by advancing the development of approximately a dozen novel molecules across haematologic and solid tumour targets in hopes of continuing to offer meaningful advances to patients in need," said David Reese, executive vice president of Research and Development at Amgen.

"We're encouraged by the early results of investigational BiTE immunotherapies AMG 420 and AMG 330, especially when considered in the context of these heavily pre-treated patients, many of whom have run out of available options. We look forward to sharing more results from our BiTE pipeline at future medical meetings."

Article by
Phil Taylor

4th December 2018

From: Research

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