- The Food and Drug Administration has halted testing for a group of cancer cell therapies from Allogene Therapeutics after a "chromosomal abnormality" was observed in a single patient who received one of the treatments, the biotech said in an announcement Thursday afternoon.
- According to Allogene, a patient who received ALLO-501a, the biotech's most advanced, experimental lymphoma treatment, experienced progressive pancytopenia, or lower-than-normal blood counts. A bone marrow biopsy subsequently detected the abnormality in the engineered cells that had been infused into the patient, leading the FDA to stop testing of ALLO-501a as well as Allogene's other cell therapies.
- Allogene will provide updates in the coming weeks as it investigates the potential cause and impact of the finding, as well as determine the next steps for the program. But the news nonetheless raises new questions about the safety of donor-derived cellular treatments, which are meant to be more convenient alternatives to the CAR-T therapies now approved for several blood cancers.
Allogene has been at the forefront of developing off-the-shelf, or allogeneic, cell therapies for cancer. So far, evidence to date has suggested they could be viable alternatives to more logistically complex cell treatments like Novartis' Kymriah and Gilead's Yescarta, which use a patient's own cells.
Allogene's earlier lymphoma treatment ALLO-501, for instance, produced response rates and a side effect profile in line with its CAR-T counterparts. There were no signs of graft-versus-host disease, a potentially deadly immune reaction and a key worry with off-the-shelf treatments using genetically engineered donors cells. The biggest question, up until Thursday, was how long the effects would last.
That has changed, however, with the discovery of a worrisome new safety finding with ALLO-501a, a souped-up version of the previous treatment and the one Allogene hand-picked for pivotal testing.
Allogene's treatment consists of donor cells that are engineered to seek out and kill cancerous cells expressing a certain protein flag. The company also uses a gene editing technology called TALEN to make changes aimed at reducing the risk of graft-versus-host disease.
In a statement, Allogene said some of the biopsied cells in a patient treated with ALLO-501a had a "chromosomal abnormality," which was detected after the trial participant experienced a series of side effects. Allogene will investigate the abnormality to see whether it has any clinical significance or is related to the gene editing involved in preparing its treatment.
"Our team is working diligently to address these questions, and we are committed to communicating updates in a timely fashion," said CEO David Chang on a conference call Thursday.
Allogene shares fell 40% in post-market trading Thursday as investors digested the news. But Chang defended the company's technology, noting that the finding is a "single case report" out of more than 100 who have been treated with Allogene's experimental therapies in clinical trials, and was seen on a "fraction" of the cells that were examined.
"It was a bit of a surprise that [the FDA] placed a clinical hold on all of our trials," Chang said.
Nonetheless, Allogene is now locked in place pending the results of the investigation, as testing of experimental treatments for multiple myeloma, leukemia and other cancers will need clearance from regulators to resume.
The length of that delay is unclear. It could drag on, for instance, if Allogene's manufacturing process is the culprit and the FDA demands modifications. Chang did reveal that the abnormality was seen on a specific chromosome that Allogene's gene editing technology targets. And that "would suggest gene editing could be at least a contributing factor," wrote RBC Capital Markets analyst Luca Issi.
But there are also multiple "confounding factors," Issi added. The patient didn't respond to several other drugs, for example, and couldn't get a standard CAR-T treatment because of a manufacturing issue.
If Allogene's technology is deemed the cause of the abnormality, an "imperfect product" may still be acceptable for cancer patients who have run out of other options, Stifel analyst Benjamin Burnett added. But an association with "genetic abnormalities with unknown consequences" would make it far less likely that the treatments could fulfill their potential in earlier treatment lines, a much larger market opportunity.
For his part, Chang said Allogene will lean on the experience he and other company executives gained at Kite Pharma, which successfully developed one of the first CAR-T treatments to market a few years ago.
"Some of us encountered, and addressed challenges with bringing one of the first CAR-Ts to market," he said. "We feel confident that we will do the same here at Allogene" with off-the-shelf treatments, he added.
Note: This story has been updated with additional detail throughout.