FDA Grants Precedence Overview to BLA of Elranatamab for R_R A number of Myeloma

The FDA has granted precedence assessment for the biologics license utility for elranatamab, an investigational B-cell maturation antigen (BCMA) CD3-targeted bispecific antibody, for sufferers with relapsed/refractory a number of myeloma (RRMM).

The BLA was based mostly on encouraging outcomes from cohort A (n = 123) of the MagnetisMM-3 trial (NCT04649359) which confirmed that therapy with elranatamab with a median observe up of 10.4 months led to an goal response charge (ORR) by blinded unbiased central assessment (BICR) of 61.0% (95% CI, 51.8%-69.6%) for sufferers with penta- or triple-class refractory a number of myeloma and who acquired elranatamab as their first BCMA-targeted remedy.2

A complete of 55.3% of sufferers handled with elranatamab had an excellent partial response or higher and 27.6% of sufferers achieved a whole remission or higher. Amongst sufferers who achieved a whole remission (n = 22), 90.9% achieved minimal residual illness (MRD)-negativity at a threshold of 10-5, and the median time to response was 1.2 months.

Though the median progression-free surivval (PFS) and total survival (OS) was not achieved, PFS charges at 6- and 12-months have been 65.2% and 58.8% with the agent, respectively. Moreover, the OS charge with elranatamab at 6 months was 76.1% and at 12 months was 63.6%.1

Moreover, these findings recommend that elranatamab has a manageable security profile because the 2-step-up priming dose routine of 12/32 mg helped mitigate the speed and severity of cytokine launch syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) amongst sufferers in cohort A handled with this priming routine.

Instances of CRS have been solely grade 1 or 2 and most circumstances have been noticed after the primary (43%) or second (24%) dose. Solely 6% of sufferers reported CRS after dose 3 and fewer than 1% skilled CRS after dose 4. Then, 3% of sufferers reported having ICANS that was grade 1/2 solely, and no deadly neurotoxicity occasions have been seen.

“At the moment, a number of myeloma is a deadly hematologic malignancy, with a median survival of simply over 5 years. As an off-the-shelf therapy, BCMA bispecific antibodies are heralding a brand new therapy paradigm that may tremendously influence the lives of individuals with this illness.” mentioned Chris Boshoff, MD, PhD, chief growth officer, Oncology and Uncommon Illness, Pfizer World Product Growth, within the press launch. “We consider that elranatamab, if authorised, has the potential to develop into the subsequent commonplace of look after a number of myeloma given its favorable scientific outcomes and handy subcutaneous route of administration. We look ahead to working with the FDA and EMA to carry this new modern medication to sufferers globally.”

MagnetisMM-3 is an ongoing, open-label, multicenter, single-arm, section 2 examine the place investigators are assessing the protection and efficacy of elranatamab alone in sufferers with RRMM. Sufferers eligible for enrollment symbolize a closely pretreated inhabitants and have had beforehand acquired at the very least 3 lessons of therapies, together with a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.2

In cohort A of the MagnetisMM-3 examine, 123 sufferers with a number of myeloma who have been refractory to at the very least 1 proteasome inhibitor, 1 immunomodulatory drug, and 1 anti-CD38 antibody have been evaluated. These enrolled had acquired a median of 5.0 prior therapies (vary, 2-22). A majority of sufferers have been triple-class refractory (96.7%) and almost half have been penta-class refractory (42.3%).1

Sufferers acquired elranatamab step-up subcutaneous dosing which consisted of elranatamab at 12 mg on day 1 adopted by 32 mg on day 4 within the first week of therapy to mitigate antagonistic occasions. After the primary week, sufferers have been administered elranatamab subcutaneously as soon as per week at 76 mg. The step-up dosing started later within the examine and included 119 of the 123 sufferers.

Amongst these enrolled, the median age was 68 years (vary, 36-89), ECOG efficiency scores of 0 have been seen in 36.6% of sufferers, 1 in 57.7%, and a couple of in 5.7%. Most sufferers have been male (55.3%) and White (58.5%). 1 / 4 of sufferers had high-risk cytogenetics (25.2%) and virtually one-third had extramedullary illness (31.7%). Additional, 15.4% of sufferers had stage III illness per the revised A number of Myeloma Worldwide Staging System, whereas the remaining had stage I (22.8%), II (55.3%), or unknown (6.5%).

Beforehand in November 2022, the FDA granted elranatamab a breakthrough remedy designation. A choice from the FDA on the applying is anticipated in 2023. Moreover, the European Medicines Company additionally accepted elranatamab’s advertising and marketing authorization utility.


Pfizer’s elranatamab receives FDA and EMA submitting acceptance. Information launch. Pfizer Inc. February 22, 2023. Accessed February 22, 2023.

Bahlis NJ, Tomasson MH, Mohty M, et al. Efficacy and security of elranatamab in sufferers with relapsed/refractory a number of myeloma naïve to B-cell maturation antigen (BCMA)-directed therapies: Outcomes fromcohort A of the magnetismm-3 Research. Blood. 2022;140(suppl 1):391-393. doi:10.1182/blood-2022-162440