FDA Lifts Hold on Cellectis’s “Off the Shelf” CAR-T, With Caveats

Xconomy New York — 

The FDA has cleared Cellectis to resume testing an experimental “off the shelf” type of cell therapy, so long as it follows a new set of measures meant to quell the safety concerns that caused the company to halt a pair of clinical trials.

Cellectis (NASDAQ: CLLS) said late Monday night that the agency will allow the company to restart the Phase 1 tests of UCART123. The treatment is a form of “CAR-T,” a type of cancer immunotherapy that just reached the market this year. The FDA has approved two CAR-T treatments from Novartis (NYSE: NVS) and Gilead Sciences (NASDAQ: GILD), each for two different types of blood cancers, since August.

But the France and New York-based firm has to add several new protective measures to its trial as part of the deal with the FDA. Among the changes: It has to lower the dose of UCART123 as well as the accompanying chemotherapy cyclophosphamide going forward, ensure that the next three patients tested are under 65, and stagger enrollment in the two studies. Cellectis said it is working to institute the changes, but didn’t say when it expects to officially restart testing.

The FDA on Sept. 4 forced Cellectis to shut down two Phase 1 trials of UCART123. A 78-year-old man with blastic plasmacytoid dendritic cell neoplasm, a type of lymphoma, died nine days following treatment after experiencing cytokine release syndrome (CRS), a common immune system reaction to CAR-T treatments, that worsened and eventually became fatal. A second patient, a 58-year-old woman with acute myeloid leukemia, also had CRS, though the condition was resolved. As a result, a data monitoring committee advised Cellectis on Aug. 28 to lower its dose of UCART123 in both studies, and the FDA suspended the studies a week later.

News of the FDA’s decision to lift the clinical hold sent Cellectis shares climbing close to 10 percent in early trading Tuesday morning, to $28.82 apiece. Shares closed at $32.18 on Sept. 1, before the FDA suspended testing.

The Cellectis studies are being closely watched because they are some of the most advanced tests of what are known as “allogeneic” CAR-T therapies, whereas the first two approved CAR-T treatments are “autologous” therapies. Autologous treatments use a patient’s own cells, meaning each procedure involves extracting those cells, shipping them off to be genetically modified, and putting them back into the patient once they’ve returned. Cellectis’s therapies are a potential threat to autologous CAR-T developers because they use T cells drawn from the blood of any donor. If they were to work, these allogeneic CAR-T treatments could be quicker and easier to develop and almost certainly cheaper than their autologous counterparts. Novartis’s therapy, tisagenlecleucel (Kymriah), costs $475,000 for a one-time treatment. Gilead’s treatment, axicabtagene ciloleucel (Yescarta), acquired through its buyout of Kite Pharma, has a list price of $373,000.

The potential problem with allogeneic treatments is the fear they may cause a catastrophic immune system reaction between the foreign cells and the patient. Cellectis hasn’t seen this happen so far, however, in humans. The safety problems in the UCART123 study were related to issues developers of autologous CAR-T have often seen in their own studies, not graft-versus-host disease.

Cellectis also has Phase 1 studies underway for UCART19 in acute lymphoblastic leukemia, though Pfizer (NYSE: PFE) and Servier own partial rights to that treatment. Cellectis wholly owns UCART123.