The trial follows the recent approval of an investigational new drug application for FCR001 by the U.S. Food and Drug Administration (FDA), and will be conducted across multiple sites in the U.S., including at Duke University and the University of Michigan.
“Individuals with diffuse cutaneous systemic sclerosis, a subset of scleroderma with high morbidity and mortality, are in great need of safe and effective, disease-modifying, treatment options,” Scott Requadt, CEO of Talaris, said in a press release. “We believe FCR001 could represent an important new approach to treating this serious condition.”
Increasing evidence supports the use of blood stem cell transplants for treating people with dcSSc — a treatment that appears to lessen organ damage and induce clinical remission in patients. But both patient-derived (autologous) and donor-derived (allogeneic) stem cell transplants pose some risk to patients.
When a transplant uses a patient’s own stem cells, patients must first receive high-dose chemotherapy and whole body irradiation to wipe out their immune system, in an attempt to decrease the risk of disease recurrence. This is a toxic treatment with detrimental side effects, such as organ damage and increased cancer risk.
“The diffuse cutaneous systemic sclerosis subset I see in my practice have very limited treatment options,” said Dinesh Khanna, MD, director of the Scleroderma Program and professor at the University of Michigan Medical School. “Autologous stem cell transplant has demonstrated the potential to induce durable remissions in randomized clinical trials, but involves significant risks to the patients.”
Alternatively, patients can receive transplants using stem cells from matched donors, but there is a risk that the donor’s immune cells see the patient’s organs and tissues as threats — a potentially life-threatening side effect called graft-versus-host disease (GvHD).
FCR001 is an investigational, allogeneic cell therapy designed to promote immune tolerance and minimize the risk of GvHD. This is achieved with a kind of nurse cells, called facilitating cells, collected from the donor that help create an immune environment that is unresponsive, or tolerant, to the recipient’s tissues. These cells also help the donor stem cells reach the bone marrow and produce immune cells.
The approach also eliminates the need to wipe out the recipient’s entire immune system, and patients require a less intensive round of chemo, called non-myeloablative conditioning, to create some room for the donor stem cells — which has fewer side effects.
“A safe, allogeneic stem cell transplant treatment using nonmyeloablative conditioning could offer important additional benefits over current autologous HSCT [hematopoietic stem cell transplantation] as a treatment for this severe form of systemic sclerosis,” said Keith Michael Sullivan, MD, professor of medicine at Duke University Medical School. “We’re very eager to study the tolerogenic potential of FCR001 for patients with severe autoimmune disease.”
Khanna added: “I am excited to participate in this clinical trial of FCR001, and hopeful that it could result in a safer and more durably effective treatment for these patients.”
The FDA’s decision to approve the testing of FCR001 for diffuse cutaneous SSc is based on the positive results from a Phase 2 trial in patients receiving a kidney transplant.
Result from this trial showed that FCR001 induced a durable immune tolerance in 70% of patients, allowing them to stop the immunosuppressive medications needed to prevent organ rejection post-transplant. Some of these patients had kidney failure due to autoimmune disease, and the treatment created such an immune tolerance that, after a median follow-up of more than five years, none of them has experienced disease recurrence.
FCR001 has been given the FDA’s orphan drug designation and regenerative medicine advanced therapy status for inducing immune tolerance in people undergoing kidney transplantation.
An ongoing Phase 3 trial, called FREEDOM (NCT03995901), is now evaluating FCR001 versus standard-of-care immunosuppression in patients receiving their first kidney transplant from a living donor. Preclinical studies assessing the feasibility of FCR001 in patients receiving kidney transplants from deceased donors are also ongoing.
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