February 3, 2021
Both Pfizer and Amgen provided updates on its BCMA bispecific programs in Q4/FY 2020 earnings calls on February 2.
- Pfizer’s BCMAxCD3 bispecific, elranatamab (PF-06863135), received FDA Fast Track designation in late January for the treatment of multiple myeloma patients who are refractory to at least one proteasome inhibitor, one immunomodulatory drug and one CD38 antibody.
- The potential registration-enabling phase 2 trial has been initiated and the first patient is expected to be dosed this month.
- In the Q&A, when asked about differentiation of elranatamab in the competitive landscape, Pfizer emphasized the 83% response rate in a heavily pretreated population with a significant number of complete responses and a nice tolerability profile with the opportunity for best-in class.
- “So although it’s filled with several entrants, I think we have an opportunity to aim for being absolutely in the first wave here and with a really nice best-in-class profile. We’re moving with first opportunity we see for accelerated approval in triple refractory patients that either have seen no prior BCMA-based treatment or have seen prior BCMA treatments such as ADC or CAR-T. So we are planning such cohorts to start soon with a potential for registration. And we’re moving into second and third line, and other combinations that are used in order to come to first and second-line opportunity.”
- The phase 1 trial of Amgen’s BCMAxCD3, pavurutamab (AMG 701), has been paused while Amgen discusses protocol modification to optimize safety monitoring and mitigation with FDA.
- This is the first time Amgen has communicated on this hold, despite a ClinicalTrials.gov update on December 18 stating that the trial was not recruiting.
- Currently enrolled patients demonstrating benefit may continue to receive treatment and enrollment is expected to resume in H1 2021.
- When asked about safety issues in the Q&A, Amgen remains “bullish” on its BiTE program and stated that “cytokine release syndrome is clearly the single challenge that sits before the entire field.”
Spinning off of the momentum and standard set by BCMA CAR-Ts, the enthusiasm for BCMA bispecifics is high, especially with its off-the-shelf capabilities and avoidance of the manufacturing and logistical components that come with CAR-T therapy. These Pfizer and Amgen announcements are important developments in determining the major players in the field, which appears to be currently led by Janssen’s teclistamab and Bristol’s CC-93269.
Pfizer is clearly making solid progress on its program and is the only BCMA bispecific in development to hold FDA Fast Track designation, which is designed to facilitate development and expedite the review of drugs, enabling more frequent communication with FDA. Besides teclistamab, this is the only other BCMA bispecific to produce clinical data from a SC formulation.
Amgen’s program for pavurutamab, a half-life extended BiTE, was highly anticipated following encouraging data for first generation BiTE AMG 420 (held FDA Fast Track status), which was ultimately discontinued due to the inconvenience of continuous weekly infusion. The safety issues disclosed on Amgen’s earnings call are a major setback in such a highly competitive space, especially given that the pavurutamab program had already underwhelmed.