ASH 2024 – Arcellx is happy to share in Car-T

Arcellx and Gilead’s BCMA-targeting Car-T anitocabtagene autoleucel (anito-cel) could soon be challenging Johnson & Johnson and Legend’s Carvykti, and one big question at ASH has been how the two assets compare. Arcellx contends that anito-cel is similar in efficacy and could be differentiated on safety – something supported by data from the registrational Immagine-1 trial presented on Monday.

However, the company also believes that the Car-T market will expand, making room for another contender. “We’ve said from the beginning, we don’t even think we need to compete directly with Carvykti, because there are so many patients who need Car-T,” Arcellx’s chief medical officer, Chris Heery, told ApexOnco during the meeting.

J&J, for its part, is also against the comparisons. “Any attempt to compare the efficacy and safety of Carvykti with anito-cel is flawed given the stark differences in sample size, populations and follow-ups,” a spokesperson said via an emailed statement.

Cross-trial conundrum

But compare people will, and investors have been unimpressed with Arcellx’s efforts at ASH so far, with its stock sinking 2% on Monday, perhaps on fears that the market might not be big enough to go around.

The presented Immagine-1 dataset, in late-line multiple myeloma, looks similar to the ASH abstract, but includes more patients.

Evolving data from Immagine-1 trial of anito-cel in 4th-line multiple myeloma

Note: *“related and unrelated”: retroperitoneal haemorrhage, CRS & fungal infection. Source: ASH 2024.

Most encouragingly, there have still been no cases of delayed neurotoxicity, either in Immagine-1 or in a phase 1 trial with longer follow-up. This could be down to anito-cel’s synthetic binding domain, said Dr Ciara Freeman of the Moffitt Cancer Center, when presenting the data. However, she added that it was hard to know for sure, given that it’s still not understood why other Car-Ts can cause this side effect.

That’s not to say that anito-cel was without issues. Grade 3/4 neutropenia was seen in 54% of patients, and there were also three deaths. These were described in the presentation as “related or unrelated”; Heery noted that one, from fungal infection, was attributed to the lymphodepleting regimen, but added that this could still be considered a risk given the patient received anito-cel too.

It’s harder to exclude a role for anito-cel in the other two fatalities but there were complicating factors, he added.

One death, from retroperitoneal haemorrhage, came in a patient who developed plasma cell leukaemia before infusion, and “shouldn’t have been treated by the definitions in the protocol”. That patient also developed grade 4 haemophagocytic lymphohistiocytosis, and underwent a biopsy to investigate this, which punctured a vein and caused the haemorrhage.

The final fatality was caused by cytokine release syndrome, in a patient with comorbidities who had rapid progression from screening to baseline, and didn’t receive bridging therapy. That case led to a change in protocol to allow bridging options, Heery said.

2026 launch goal

He wouldn’t disclose when anito-cel might be filed with regulators, but stuck to Arcellx's previous estimate of launch in 2026.

If anito-cel does reach the market, Heery reckons that manufacturing could be another potential differentiator. The Car-T is being produced by Gilead, via its Kite subsidiary, and “when we launch, it’s very likely that anito-cel will be available in more centres than even Carvykti, because Kite already has relationships with 300-plus centres around the world". 

"We think we’ll not have some of the difficulties you’ve seen with other Car-T launches, because of [Kite's] ability to manufacture at scale already."

While Carvykti and Bristol Myers Squibb/2seventy bio’s rival BCMA-targeting Car-T Abecma are set to make over $1bn between them this year, Heery reckons the second-line-plus Car-T multiple myeloma market could eventually be worth $12bn – and could become even larger if Car-T ever goes first line.

“Most people ask us is: isn’t it going to be so difficult, going against J&J and Legend?” Heery concluded. “But even J&J has said it’s probably only going to address about half of the market with its manufacturing capability. That’s why we always felt there needed to be another player.” Next up will be convincing regulators, and doctors.