The market for allogeneic stem-cell transplants continues to grow. “We’re seeing an increased interest in allogeneic approaches and being able to have something readily available off the shelf,” said Joy Aho, senior product manager at Be The Match BioTherapies.
The momentum of this growth is likely to continue for allogeneic therapies into 2022 as researchers continue work on allogeneic chimeric antigen receptor (CAR)-T cells, CAR-NK (natural killer) cells and other therapies.
By contrast, the supply chain for autologous therapies is more complicated. “You’re also harvesting material from very sick patients, which is not ideal from a manufacturing standpoint,” Aho said.
If there is an autologous manufacturing failure, it becomes necessary to collect blood stem cells from the patient. In some cases, a patient may be too sick for another blood draw.
Such factors could put the brakes on the growth of autologous therapies, which still
“There’s a lot of those issues in autologous even with all of the upside,” Aho said.
Consistent growth likely for cell and gene therapy, too
The cell and gene therapy market has grown steadily, even during the pandemic. “In general, you saw continued development — you saw continued trials being initiated,” Aho said.
“We saw pauses and slowdowns in some of the existing trials,” Aho said. Such slowdowns were partly the result of drops in patient accrual resulting from the pandemic. Early trials tended to face more of a slowdown than Phase 3 studies. “For the bulk of these therapies, [sponsors] are treating patients with a final line of therapy.”
Expect continued regulatory scrutiny for allogeneic therapy
There have been a couple of examples of potential safety signals in allogeneic therapy. In October, Allogene Therapeutics announced that FDA had placed a hold on its AlloCAR T clinical trials after identifying a chromosomal abnormality in a patient enrolled in its ALPHA2 study. FDA is aiming to ensure there is a clear “characterization of those cells and understanding the potential risks going into that therapy,” Aho said.
Recently, Nature Medicine described the case report of a multiple myeloma patient who developed Parkinsonism symptoms three months after receiving a form of CAR T-cell therapy. The study used autologous T lymphocytes transduced with LCAR-B38M, a lentiviral vector used to express a CAR targeting the human B cell maturation antigen.
“When it’s autologous therapy, it’s your own cells. So there’s a lot of areas where there’s much less risk,” Aho said. “When you get to allogeneic therapies, then, there are a lot more considerations there in making sure that that starter material is properly characterized and everything happening, and that bar goes even higher.”
The risk is also potentially higher in therapies like induced pluripotent stem cells (iPSC) and regenerative medicine therapies when researchers aim to place a cell in the body that permanently resides there. “You could be doing something regenerative with diabetes treatment or something like that, then that bar has to be really high — those cells can’t go off the rails versus a lot of the therapies today,” Aho said. “When you think of T cells and NK cells, they’re not designed to stay there forever. They’re in there to do a job, and then they go away.”
Induced pluripotent stem cells remain a promising, if early, experimental therapy
Induced pluripotent stem (iPS) cell-based therapy offers significant potential for various diseases. For diabetes, for instance, researchers have explored differentiating the primitive stem cell-like cells into islet-like cells for diabetes patients. “It would be a cell replacement therapy,” Aho said.
BlueRock Therapeutics has a regenerative program for Parkinson’s disease. “They generated neurons in a dish. They’re frozen down, and then they’re put back into the brains of Parkinsonian patients.”
BlueRock got the Fast Track designation from the FDA for DA01, a pluripotent stem cell-derived dopaminergic neuron therapy. Blue Rock is also raised $225 million to develop potential stem cell therapies for heart damage.
Similarly, Fate Therapeutics (NSDQ:FATE) is developing NK cell therapies from iPS. Sana Biotechnology also has made a significant investment in developing similar therapies.
While such potential therapies offer considerable promise, there likely will be few tangible breakthroughs in the near term. “It’s not like going to be in the next couple of years,” Aho said. When you’re putting something in the body that’s meant to stay, you know, for the rest of your life, then that bar has got to be really high in terms of how you’re characterizing the cells,” she added. “It will be interesting to see what the FDA is going to require from that perspective.”
Filed Under: clinical trials, Drug Discovery