Plant maintenance poses supply blips as BCMA CAR-T rivalry heats up

Legend Biotech says it will take a “smart approach” to Carvykti’s routine manufacturing maintenance after rival Bristol Myers Squibb warned of sales disruption for its BCMA CAR-T, Abecma.

For its second quarter 2023, Bristol Myers Squibb reported worldwide sales for its B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy Abecma (ide-cel) of $132 million, up 48% year-on-year.

However, during its financial call, the company warned stakeholders the upwards trajectory of the therapy seen since its approval for the treatment of multiple myeloma in March 2021 is likely to be interrupted in Q3 due to a maintenance-related shutdown at its plant in Summit, New Jersey.

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According to management, the manufacturing maintenance took place in June in anticipation of the outcome of the firm’s KarMMa-3 trial, which would approve Abecma as an earlier line of treatment for multiple myeloma. Currently Abecma is approved as a fifth line treatment.

Due to the planned manufacturing maintenance, “we expect third quarter revenues to be lower than second quarter revenues,” said CFO David Elkins, though Bristol Myers expects “a significant increase in volume in the fourth quarter.”

The firm has a second commercial CAR-T, Breyanzi (liso-cel), but chief commercialization officer Adam Lenkowsky said this therapy was not affected as the shutdown took place at the S12 building, dedicated to Abecma.

“All of our shutdowns are planned [and] accounted for in our capacity plans,” he said. “This is routine shutdown to execute maintenance at our site for approximately one month. “The ramp[-up] for Abecma is really tied to overall supply plans with KarMMa-3 being one important aspect of that ramp[-up]. And that’s important because we now have over 90% manufacturing success rates and multiple ramp[-ups] since launch. So, this routine manufacturing maintenance process is really important for us to continue our strong success rate and build our readiness for increase capacity in advance of the KarMMa-3 launch.”

Legend Biotech, which brought its own BCMA CAR-T Carvykti to market in March 2022, told its stakeholders that both itself and partner Janssen (part of J&J) are subject to similar, and regular, maintenance demands within its manufacturing network.

“For any aseptic GMP manufacture every year you are required by FDA to do this kind of maintenance,” CEO Ying Huang said last week. “However, our operation from the Janssen and Legend teams in New Jersey, we have decided to take a very smart approach which is, we’re not going to shutdown facility at all. Instead, we’ll do a rotation from all the different suites.

“So, yes, every six months, we will have to do the so-called aseptic simulation run. But it really wouldn’t affect the revenues so much that you’re going to see a quarter-over-quarter decrease here. So we are planning for this margin and we will obviously conduct all the required aseptic processes for the rest of the year. But suffice to say, we’re not planning a shutdown of the facility.”

Huang also alluded to recent efforts to ramp up supply, especially with its ongoing CARTITUDE trial that hopes – like KarMMa-3 – to bring approval for the therapy as an earlier line of treatment. This includes the three-year contract signed with Novartis to manufacture additional clinical doses of Carvykti in April, and 35 treatment centers added this quarter.

For the three months ending June 30, Legend saw collaboration revenues for Carvykti of $58 million, up 26% year-on-year.