J&J, Legend's Carvykti delivers encouraging early growth ahead of key myeloma readout

In hot pursuit of Bristol Myers Squibb and 2seventy bio’s first-to-market Abecma, Johnson & Johnson and Legend Biotech’s CAR-T therapy Caryvkti has shown an encouraging sign of growth.

Caryvkti pulled in $55 million in sales in the third quarter, Legend said in a securities filing (PDF) Tuesday, citing J&J’s data. That was up from $24 million in the three months ended in June, the first full quarter the multiple myeloma drug was on the market. J&J has projected Carvykti could reach $5 billion in global sales.

Caryvkti is in closely watched competition with BMS’ Abecma. Both BCMA-targeted CAR-Ts are now relegated to myeloma patients who’ve failed at least four prior lines of treatment. In the third quarter last year, which was Abecma’s second quarter on the market, the BMS drug generated $71 million sales.

Unlike BMS, J&J and Legend are taking a phased approach to Carvykti’s launch, gradually scaling up availability and the number of treatment centers based on constrained manufacturing capacity. The Carvykti developers hope to avoid the supply confusion Abecma has experienced.

That’s not to say Carvykti can meet all demand at the centers it has already activated. To increase supply, J&J and Legend are doubling their investment in a Raritan, New Jersey, cell therapy manufacturing facility to a total of $500 million, Legend CEO Ying Huang, Ph.D., said at a recent investor event.

The new commitment comes as the pair expects a potential spike in demand if Carvykti moves to earlier treatment settings. The anticipated expansion depends on a readout from the CARTITUDE-4 trial, which is evaluating Cavykti in patients who had taken one to three prior lines of therapy. The trial is expected to report data by yearend, Jennifer Taubert, J&J’s pharma chief, said during the company’s third-quarter earnings call Tuesday.

Also eyeing earlier treatment, BMS has already announced positive outcome from Abecma’s KarMMa-3 trial, which is one treatment line behind CARTITUDE-4.

One “extremely important” difference between the two trials is that CARTITUDE-4 doesn’t require prior treatment with J&J’s Darzalex, Steve Gavel, Legend’s vice president of global cell and gene therapy commercial development, said during the company’s investor event. Despite Darzalex’s FDA approvals in newly diagnosed multiple myeloma a couple years ago, about 80% of second-line patients still haven’t been treated with the CD38 antibody, Gavel noted.

A second-line indication would cover about 36,000 U.S. patients, potentially tripling Carvykti’s eligible patient pool, Gavel said. Anticipating that “major inflection point,” and backed by the manufacturing expansion, J&J and Legend also plan to increase Carvykti’s treatment sites to about 80 from the current 40.

Meanwhile, hospitals are increasingly looking to administer CAR-Ts in the outpatient setting because of limited resources such as bed space thanks to an influx of commercial and clinical CAR-T and gene-editing therapies. In that setting, Carvykti holds an advantage, Steve Gavel, Legend’s vice president of global cell and gene therapy commercial development, said during a recent investor event. 

The main reason to keep a patient hospitalized is to monitor for a potentially dangerous immune side effect known as cytokine release syndrome (CRS). Carvykti has been linked to a relatively late onset of CRS compared with Abecma, allowing doctors to manage patients in an outpatient setting, Gavel explained.

Shifting to outpatient treatment could open a CAR-T therapy such as Carvykti to more patients by reducing constraints on the drug administration side.