Patient death mars latest cut of data from Allogene's off-the-shelf CAR-T
Allogene has been riding high since ASCO in May, when early data showed their off-the-shelf CAR-T worked in a handful of patients and that no one rejected their foreign cells. It was a key moment in a field that could remake cell therapy and treatment for certain cancers.
On Wednesday, though, the Arie Belldegrun-founded biotech released results for their multiple myeloma CAR-T and, although the responses were there, so was a red flag: Four patients contracted a serious infection, and one of them died.
Allogene $ALLO shares immediately fell from $33.79 to $28.78 Wednesday morning, although they would rebound to $31.06 by the time markets close.
The news is tragic on its own and a setback for an approach that Allogene is trying to prove can compete with or even outperform traditional multiple myeloma CAR-Ts from J&J and Legend and from Bristol Myers Squibb and bluebird. Although Allogene and startups such as Poseidon have pointed to the potential for off-the-shelf approaches to be more scalable and allow for repeat dosing, J&J and bluebird have already shown strong efficacy in human trials, setting the bar high.
Still, analysts were divided on how large a role Allogene’s treatment played in the patient’s death, or how concerned they should be if they are. The volunteers in the Allogene trial were very sick, with many on their fifth-line of therapy for a deadly cancer, and patients have died throughout the last decade of CAR-T trials, including in the bluebird studies.
Cowen’s Marc Frahm said it was “unsurprising” news. “We would note that several other CAR T cell trials [saw] infections including fatal events,” he wrote in a note to investors.
The patient was diagnosed with severe pneumonia eight days after receiving the therapy, and investigators attributed it to the intense chemotherapy patients undergo directly before receiving the therapy. They added that, as of the data cutoff for the abstract, they had not seen other major adverse events, including graft versus host diseases — one common and damaging side effect from other form of cell transplants.
Jefferies’ Biren Amin noted that, more broadly, “high infection rate is a key factor for mortality in myeloma patients.”
Analysts, meanwhile, were largely satisfied with the efficacy results. Although it’s still early in Phase I, they argued it showed the potential to eventually compete with the J&J and bluebird CAR-Ts.
In the high-dose arm of the dose-finding study, three out of five patients responded. One of the three had a stringent complete response and another had a very good partial response.
That’s a pretty small sample size to draw percentages from, but Frahm argued it looked “similar” to the roughly 65% VGPR/CR response bluebird saw in early studies and the 88% VGPR response J&J saw.
Amin said it showed high doses are needed for the therapy to work. He said longer term, they’ll be looking for Allogene to match bluebird’s Phase I results. In that study, he noted, patients across dose cohorts who had high BCMA expression had an 89% response rate and a 22% complete response rate.