ORLANDO — The future of treating the most advanced patients with the blood cancer multiple myeloma lies in a single protein on tumor cells.
Called B-cell maturation antigen, this protein is more common on diseased cells, making it an appealing target for drug developers looking to wipe out the cancer without affecting healthy tissue.
This hypothesis has drawn biopharma companies into the fray, with three different strategies in play: Weaponizing the body's own immune cells to identify and kill diseased cells; using another protein that binds with the antigen to deliver a killer dose of chemotherapy; or using a dual-acting protein that will pull cancer-fighting immune cells into cancerous cells.
All three of these approaches were on display at the American Society of Hematology's annual meeting, held in Orlando this past weekend. The strategy of turning immune T cells into precision tumor-fighting tools is closest to reaching patients broadly, as Bristol-Myers Squibb and Johnson & Johnson expect to have their candidates before regulators next year. But the race is on to get other BCMA-targeted treatments on the market.
CAR-T treatments are already approved for patients with certain types of lymphomas and a type of pediatric leukemia.
The drawback of this style of treatment is that it requires patient T cells be removed from the body and then re-engineered in a process that can take a few weeks. After which, the newly modified cells are re-injected as chimeric antigen receptor T cell therapies, or CAR-T.
This takes place at specialized centers to which many patients may not be able to travel. Even if they can, the process may be too burdensome, said Joseph Mikhael, a professor at Translational Genomics Research Institute in Arizona and chief medical officer of the International Myeloma Foundation.
"I can't easily see a world where even 51% of myeloma patients could even have access to CAR-T. It can't be the solution," Mikhael said in an interview. "Whereas, for these off-the-shelf-like drugs, it's a bit more convenient: They go into the clinic, they get it, they leave."
Nonetheless, the data presented on CAR-T look compelling, with Johnson & Johnson's JNJ-4528 having cleared out cancer cells in all 29 patients dosed, with 20 achieving remission, in an early-stage study.
"When we've looked at the ability to deliver a very deep, early responses and having them be durable, we see that profile is more commonly achieved with our BCMA" than with alternative treatment strategies, said Craig Tendler, J&J's vice president for late stage development of hematology, oncology and supportive care, in an interview.
The day before ASH kicked off, Bristol-Myers Squibb and biotech partner Bluebird bio announced data from a pivotal trial of the CAR-T they call idecabtagene vicleucel, or ide-cel, which showed the therapy spurred tumor responses in 73% of patients across three dosage groups.
Patients went nearly nine months before their disease progressed, about three months less than in an early update on the trial in 2018. That reduction in progression free survival was expected, wrote Piper Jaffray analyst Tyler Van Buren in a note to clients on Dec. 8. He said the data presented by the two partners suggest that ide-cel is good enough to win approval from the Food and Drug Administration.
Other companies are betting that the share of patients who choose the off-the-shelf therapies will be large enough to justify spending money on their research and development. Among those are Regeneron Pharmaceuticals, Amgen, GlaxoSmithKline and Pfizer.
"When we looked at CAR-Ts, we said, 'Gee we don't think it has to be this complicated,'" said Israel Lowy, head of translation science and oncology at Regeneron, in an interview.
Regeneron featured early data from its "bispecific" antibody REGN 5458, which binds to BCMA and a protein called CD3 that is expressed on infection-fighting T cells. This aids in activating the immune system to fight the disease.
The data is only in seven patients from a dose-finding trial. Four of them saw their disease subside and two patients in the highest dose group were judged to have "minimal residual disease," or no detectable level of diseased cells.
Lowy said the results seen so far have encouraged Regeneron to begin planning a larger study intended to be used for FDA submission.
The third approach, called "antibody drug conjugates" for their combination of a targeting protein with a chemotherapy, is best exemplified by GlaxoSmithKline's belantamab mafadotin.
The British big pharma didn't have any major updates at ASH to the data it's collected so far, but has said it plans on submitting the agent to the FDA by the end of 2019. An impressive 60% response rate reported earlier is tempered by eye pain suffered by patients receiving the treatment in clinical study.
The companies backing CAR-T have decided it's not the only arrow in their quivers. Both J&J and Bristol-Myers Squibb, thanks to its Celgene acquisition, have bispecific antibodies in the guise of JNJ-7957 and CC-96239, respectively.
"I think there's a role for both and it's going to be very patient-specific," J&J's Tendler said. "There are those patients that maybe can't wait for a CAR-T that takes three or four weeks to manufacture and maybe they need bispecifics to bridge them to the CAR-T."
Bristol-Myers also has an early antibody-drug conjugate from Sutro Biopharma, giving it a complete or — less generously, redundant — portfolio of BCMA-targeting therapies in testing.
"We think BCMA is a terrific target," said Stanley Frankel, head of cell therapy development at Bristol-Myers Squibb, in an interview.
"I think there is going to be room either for the individual patient, or for groups of patients, to get one or more of these. It's going to take a few years to figure out who gets what and when."
Ned Pagliarulo contributed reporting.