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With new Allogene data, same promise, questions surround 'off the shelf' CAR-T.

Allogene Therapeutics, a front-running biotech in the race to develop "off the shelf" cell therapies for cancer, on Friday disclosed updated results from 19 lymphoma patients who received its treatment in an early trial. The company gave an initial look at data from nine patients earlier this month. The new details, unveiled as part of the American Society of Clinical Oncology's virtual annual meeting, include more recently treated patients and longer follow-up.

Results are among the most substantive to date for an off-the-shelf, or allogeneic, CAR-T therapy. They show a treatment profile that a study investigator called "comparable" to what would be expected from the more complex "autologous" treatments, like Yescarta and Kymriah, that are now available.

But they don't provide much new insight as to how long patient responses will last, a key question for Allogene and others to answer as more allogeneic treatments are tested.

If successful, an allogeneic approach could make CAR-T cell therapy — which has struggled commercially and requires a multi-week manufacturing and delivery process — more accessible. Patients in Allogene's study went a median of only five days to receive treatment after enrolling.

Since mid-May, when Allogene first revealed initial results from its trial, shares in the company have jumped nearly 60%.

While early and with plenty of caveats, Allogene's data offer at least the potential that a cancer cell therapy derived from healthy donors might be a viable alternative to autologous CAR-T treatments, which are made from the cells of cancer patients.

Results are from 19 patients with either large diffuse B-cell lymphoma or follicular lymphoma, who were treated with Allogene's therapy, called ALLO-501, a median of 3.8 months ago. In May, the biotech reported data on 9 patients who had a median of 2.7 months of follow-up.

The update shows the same promise, according to the study's lead investigator, Sattva Neelapu, a professor in the Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center.

"What we're seeing so far is in the same ballpark, if not slightly better — at least in terms of safety — compared to the existing autologous CAR-T products," Neelapu said in an interview with BioPharma Dive.

Previously, Allogene had reported that seven of nine evaluable patients, or 78%, responded to ALLO-501, with three showing no trace of cancer and the other four having partial responses. Now the company says that 12 of 19, or 63%, evaluable patients responded, seven of them to the point that no cancer could be detected.

While the response rate is now lower, Allogene said that's because it recently enrolled four patients who had failed autologous CAR-T treatment or progressed within three months. Three didn't respond, and the fourth hasn't been evaluated yet.

"There is something unique about their tumors" that prevents CAR-T from working, CEO David Chang told BioPharma Dive. Allogene won't enroll any others who previously failed autologous CAR-T.

Allogene's treatment regimen also includes an antibody drug, ALLO-647, that, along with two chemotherapies, is meant to prep patients for treatment and boost the effectiveness of the cell therapy.

The new data provides more detailed information on both points, and includes results from the first eight patients to get a high dose of the antibody. Four of the eight had complete responses, versus three of the 11 on a low dose.

Neelapu said the numbers offer a "hint" that the higher dose might help, but more data are needed to draw any definitive conclusions.

Just like its initial peak, Allogene still reports that no patients developed graft-versus-host disease, a potentially deadly condition and a key worry with a treatment that puts foreign cells into the body. Six patients experienced cytokine release syndrome, an immune system overreaction often seen with CAR-T treatment, but most cases were classified as mild or moderate. All resolved within seven days.

Allogene reported a total of four severe side effects, and three of them included viral infections.

Neelapu said those infections were picked up on screening tests and were easily treatable. At least thus far, a higher dose of ALLO-647 hasn't meant an increased risk of those infections, he said.

Optimally, off the shelf treatments could expand the use of CAR-T. Autologous therapies take two to three weeks to make and deliver, by which time patients' disease might progress, and that means many who might need the therapy can't get it.

Even those that do get treated need lengthy hospital stays. Yescarta patients have to be monitored for at least a week post-treatment, and one study published last year from Vizient estimated the median stay post-treatment to be 15 days, adding a big hospital bill on top of an already pricey therapy.

Allogeneic therapies are quicker to make; it took a median of five days to treat patients in Allogene's trial. That, and more evidence of improved safety, could mean such treatments are more widely accessible.

"I definitely see an opportunity to develop this more as an outpatient" procedure, Chang said.

That's provided, however, that allogeneic treatment will last as long as autologous cell therapy. Nine of the 12 responses Allogene has seen thus far were ongoing as of the latest data cutoff, meaning no additional patients had relapsed yet.

Author:Ben Fidler

Published: May 29, 2020

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