Novartis ended all of their gene therapy programs which were oncology related in 2016. Unfortunately, that meant an end to many programs that still had potential. This included cell therapy work by Suzanne IIdstad, which many believed had extreme promise for organ transplant patients.
Suzanne has been working on this therapy since 2002 when she first founded her company Regenerex (also known as Talaris Therapeuitcs). She is a transplant surgeon, a professor at the University of Louisville, and the Director of the Institute of Cellular Therapeutics. Her therapy is called FCR001.
Novartis first partnered with Regenerex in 2012 following positive data from Suzanne’s Phase 2 study of FCR001 in patients undergoing kidney transplants. This study was possible thanks to grants from the US Department of Defense and the NIH. The results from this investigation were published in Science Translational Medicine. Novartis licensed the technology from Regenerex in 2013.
Sadly, when Novartis ended their gene therapy program in oncology, the FCR001 program was temporarily put on hold. But thankfully, Regenerex has just received 100 million dollars in a Series A investment from Blackstone Life Sciences with which they can continue their investigation of FCR001 and finally initiate a Phase 3 clinical trial. This trial should begin by the end of this year. Researchers say they already have a list of patients ready to enroll.
Over 113,000 people are currently on the organ transplant list in the United States. 84% of these individuals are waiting for a kidney. The average wait time for a kidney from a deceased donor is 3-5 years. Patients do have the option of finding a living donor, reducing this wait time to a year. However, finding a well-matched donor is extremely difficult as there are many factors which can result in rejection.
When a patient’s body sees the new organ as a threat, it attempts to destroy it. This is called Graft versus host disease (GvHD). To combat this rejection, many organ transplant patients are forced to take immunosuppressive drugs for the remainder of their life. Unfortunately, these drugs come with their own complications. They increase the risk of infection and can cause heart problems. In fact, between the years of 1996 and 2014, heart disease was actually the leading cause of death of kidney transplant patients in the United States.
For decades researchers have attempted to find a solution to this problem. Cell therapies have indicated potential. However, not enough studies that are large enough to prove efficacy have been undertaken.
Essentially, FCR001 is a one-time cell therapy in which kidney transplant patients are given an infusion of their donor’s stem cells. These cells enter the bone marrow where the donor’s cells mix with the patient’s cells. The cells which help the donor’s cells move to the bone marrow are called facilitating cells. These cells promote immune tolerance. Once in the bone marrow, the donor’s cells start to make red and white blood cells. These new cells fool the patient’s immune system, causing them to see the new cells as their own even though they contain genes from the donor. This effectively reduces the chance that the patient’s body will reject the kidney from the donor.
Ultimately, this therapy, if proven successful, could allow patients to 1) receive a kidney from any donor and 2) not necessitate a life-long course of immunosuppressive drugs.
2019 follow-up data from Suzanne’s Phase 2 study of FCR001 showed that 26 out of 47 patients treated with the therapy were living without taking immunosuppressive drugs. Many of these individuals had not had a perfectly matched donor.
It is important to note that two cases of GvHD were documented in this trial and one individually sadly died from the diagnosis. These two individuals were found to share distinct characteristics, and donors/patients with the same characteristics will not be allowed to enroll in the Phase 3 study.
Researchers also believe that this therapy could be utilized for autoimmune diseases, some of which cause kidney failure in the first place. While the specific autoimmune diseases FCR001 is also being studied for have yet to be released, scleroderma was mentioned previously. Phase 2 investigations for these diseases could potentially start this year, so keep an ear out.
Ultimately, there’s still a lot of unknowns in this investigative therapy, however there’s also a lot of promise.
You can read more about the investigation of this therapy here.