6:15 PM
Dec 15, 2017
 |  BioCentury  |  Product Development

Assessing the BCMA scene

Why it’s too soon to call bluebird’s bb2121 the winning BCMA CAR at ASH 2017

Differences in patient populations and a dearth of clinical outcome data mean it’s too soon to declare bluebird bio Inc.’s anti-BCMA chimeric antigen receptor therapy the leader of the pack of CARs that presented clinical data in multiple myeloma at the American Society of Hematology meeting.

While the CAR data do hint at unprecedented benefits for targeting BCMA, they don’t shut antibody-drug conjugates (ADCs) and other anti-BCMA modalities out of the fold; these will likely still have a place in the arsenal for MM patients unable to access or tolerate CAR T regimens.

BCMA (TNF receptor superfamily member 17; TNFRSF17; CD269) has emerged as the next hot target in CAR T therapies. At least 10 BCMA-targeted CAR T cell therapies are in the clinic to treat multiple myeloma. Of those, six reported clinical data at ASH, which ran Dec. 9-12 in Atlanta (see “New Targets for CAR Ts”).

If approved for MM, BCMA-targeted CARs would address a more prevalent cancer than the indications of currently approved CAR therapies, acute lymphoblastic leukemia (ALL) and diffuse large B cell lymphoma (DLBCL). The National Cancer Institute estimates 30,280 new cases of myeloma will have been diagnosed in the U.S. in 2017, compared to 5,970 cases of acute lymphoblastic leukemia (ALL). NCI estimates 72,240 new non-Hodgkin’s lymphoma (NHL) cases will be diagnosed, of which 31% (about 22,000) tend to be DLBCL.

BCMA promotes plasma cell survival and plays a role in growth and survival of myeloma cells. Its expression is limited to B cells in later stages of development and it is almost universally present on myeloma cells.

Going into ASH, expectations for anti-BCMA therapies were high in part because of a June presentation at the American Society of Clinical Oncology meeting where Nanjing Legend Biotech Co. Ltd. reported that all 19 evaluable patients (100%) responded in the first phase of the Phase I/II LEGEND-2 study of LCAR-B38M to treat relapsed or refractory MM.

Nanjing Legend is a subsidiary of Genscript Biotech Corp.

“There are some innate differences in these studies that make that comparison unfair at this moment.”

Anita D’Souza, Medical College of Wisconsin

At ASH, multiple analysts were quick to declare bluebird’s bb2121 the best of the bunch, and the biotech’s stock gained $30.65 (18%) to $201.80 on Monday, adding over $1.4 billion in market cap, after reporting near universal responses among active dose cohorts in the escalation portion of the CRB-401 Phase I trial (see “ASH Movers”).

Though the expansion phase of CRB-401 is ongoing, bluebird and partner Celgene Corp. have started enrolling patients in the single arm, open-label Phase II KarMMa study, intended to support regulatory submissions in an undisclosed time frame.

Three doctors who spoke to BioCentury agreed the BCMA data sets presented at ASH show the therapies are indisputably active in MM and would have a place in the treatment arsenal. But they weren’t ready to declare a winning program.

“There are some innate differences in these studies that make that comparison unfair at this moment,” said Anita D’Souza, an assistant professor of medicine in the Medical College of Wisconsin’s Division of Hematology and Oncology.

Figure: New targets for CAR Ts

This year’s American Society of Hematology meeting in Atlanta saw a wave of data for chimeric antigen receptor T cell products targeting proteins beyond CD19. The most clinically advanced of these were also the most common, with CAR T therapies targeting BCMA (TNF receptor superfamily member 17; TNFRSF17; CD269) topping the list.

At least seven abstracts contained clinical data for anti-BCMA CAR T therapies to treat multiple myeloma (MM), while 10 more reported preclinical data for CAR Ts against the target. Anti-CD22 CAR T programs were the subject of at least six abstracts containing clinical data in acute lymphoblastic leukemia (ALL), the indication for which anti-CD19 therapy Kymriah tisagenlecleucel from Novartis AG (NYSE:NVS; SIX:NOVN) is approved. The preclinical abstracts describing CAR T cells against CD22 also include two preclinical abstracts on bi- and trispecific CAR T therapies that target CD22 along with CD19 and/or CD20.

Abstracts were identified by searching for the words “chimeric antigen receptor” or “CAR,”...

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