There is a noteworthy update this afternoon in the long-running effort to turn cells from healthy donors into effective cancer treatments — data suggesting an experimental therapy from Allogene Therapeutics may help very sick patients with non-Hodgkin lymphoma.
The data, though, are a preliminary snapshot from nine patients in an early-stage trial. Released in an abstract ahead of the American Society of Clinical Oncology's annual meeting later this month, they're meant to show a regimen that includes Allogene's cell therapy ALLO-501 and its antibody drug ALLO-647 is safe, and to determine the best dose to take forward.
Much more testing is needed to establish the worth of the therapies, and the company will give updated details at the ASCO meeting this month. Nonetheless, the results represent one of the more substantive looks to date at allogeneic, or "off the shelf," cell therapy, in which cells from healthy donors are genetically modified to seek out tumors.
Companies developing these treatments are aiming to show they're as effective and safe as "autologous" therapies — which use cells taken directly from the cancer patients they're attempting to treat — while also being less challenging to produce.
"The ease of making the products is amazing," said Stephan Grupp, the director of the cancer immunotherapy program at the Children's Hospital of Philadelphia, who isn't involved with Allogene.
That ease, in part, is why large companies like Pfizer, Johnson & Johnson and Bayer have each made notable investments in the field. Allogene is among them, having been formed in 2018 with $300 million and a portfolio of treatments that originated within French firms Cellectis and Servier.
But there's much to prove. Two autologous treatments, known as CAR-T therapies, from Gilead and Novartis are on the market, while no allogeneic therapy has made it through to even a late-stage trial. It's also unclear whether their effects will last as long as their autologous counterparts, or trigger dangerous immune responses, a significant possible pitfall since allogeneic treatments use foreign cells.
Should allogeneic therapies eventually come to market, their developers would be under pressure to succeed commercially where autologous treatments have faltered. Both Gilead and Novartis struggled to ramp up sales for their cell therapies after gaining initial U.S. approvals in 2017.
The results announced Wednesday come from a study of patients with either follicular lymphoma or large B-cell lymphoma — two forms of NHL — and had failed at least two prior treatments. The patients received two chemotherapies commonly used in CAR-T conditioning regimens, fludarabine and cyclophosphomide, and ALLO-647, an antibody drug meant to prep patients for treatment and boost the cell therapy's effectiveness.
They then received treatment with the CAR-T therapy itself, ALLO-501, which is engineered to seek out a protein commonly expressed on malignant B cells.
As of a January cutoff, seven of nine patients, or 78%, responded to treatment. Three of the responders had no trace of cancer, while the other four had partial responses after a median 2.7 months of follow-up. Three of those patients saw their disease progress after two, four and six months respectively. Allogene has yet to disclose which doses of ALLO-501 these patients got. They all received low doses of ALLO-647.
"We feel good and reassured by the kind of results we're seeing," said CEO David Chang, in an interview.
Importantly, Allogene reported that no patients developed graft-versus-host disease, a potentially deadly condition when the new cells attack the body. Two patients had mild or medium cases of cytokine release syndrome, a common immune system reaction to CAR-T treatment. One had a low-grade neurological side effect that resolved without treatment.
But one patient also had multiple minor viral infections, which Grupp flagged as something to watch as Allogene prepares to report more detailed results at ASCO.
There's "clear proof of concept," Grupp said in an interview, "but still some concerns about what infectious toxicities might come along with [ALLO-647]." Grupp reviewed the data at BioPharma Dive's request on condition he not share any information.
Chang pointed out that these were "uneventful," manageable infections, but acknowledged that their frequency is "something that we would be very interested in" as the study numbers increase.
So will the staying power of responses to ALLO-501. Gilead's CAR-T therapy Yescarta — which Chang helped develop when he was an executive at Yescarta's original developer, Kite Pharma — was approved for NHL based on 73 out of 101 patients responding to treatment, with the effects lasting a median of 9.2 months. Chang said Allogene is shooting for responses that "go on for more than a year."
Grupp said he would like to see responses lasting at least six to 12 months. Then "you can make the argument for a persistent clinical effect," Grupp said.
Still, it's unclear whether an allogeneic therapy would have to match an autologous CAR-T given the convenience advantage. Chang noted, for instance, that cancer patients can have their cells collected for autologous CAR-T therapy but never actually get the treatment because of complications or disease progression that might occur while they wait for it to be made.
Novartis and Gilead currently need between two to three weeks to deliver a completed CAR-T therapy, measuring from when cells are extracted from a patient, to when the engineered versions are infused back in.
An allogeneic therapy, meanwhile, would "be able to treat all of those patients rather than lose them," Chang said. Any decision on which type of treatment to use, though, would ultimately be made by physicians, and opinions vary on what allogeneic CAR-T would need to show in order to be convincing.
Allogene is starting a Phase 1 study of a similar, next-gen product, ALLO-501a, within weeks, according to Chang. The difference between the drugs is that ALLO-501 has a "safety switch" built in, through which the drug Rituxan can shut down the engineered cells. ALLO-501a doesn't, which would make it more viable as a treatment for NHL, for which Rituxan is a common therapy.
The Phase 1 study in ALLO-501 was meant to answer key questions that should apply to ALLO-501a, Chang said. A Phase 2 trial should start next year.