Development status for IdeS

The clinical development program is currently focused on treatment prior to kidney transplantation. The long-term vision for Hansa Medical is to establish IdeS as a therapy for fast and efficient elimination of pathogenic IgG in several transplant-related indications and acute autoimmune diseases.

IdeS has been evaluated in a Phase I study in healthy subjects and in two finalized Phase II studies in sensitized patients awaiting kidney transplantation. The results from these studies demonstrate that IdeS is highly effective in reducing anti-HLA antibodies to levels acceptable for transplantation and is well tolerated.

The efficacy and safety of IdeS is currently being investigated in two ongoing Phase II studies in highly sensitized kidney transplantation patients. Patient recruitment was completed in early January 2018 to these two Phase II studies and the patients will be monitored for six months with respect to safety, kidney function and levels of donor-specific antibodies (DSA). Results from these two studies are expected by third quarter 2018.

An investigator-initiated Phase II study with IdeS in the rare and acute autoimmune kidney disease anti-GBM antibody disease is ongoing in collaboration with several European nephrology clinics. Additional Phase II studies with IdeS are being planned within acute antibody-mediated rejection (AMR) and treatment of the acute autoimmune neurological disease Guillain-Barré syndrome (GBS).

Dr Tomas Lorant

Interview with Dr Tomas Lorant, Consultant Transplant Surgeon at Uppsala University Hospital, Uppsala, Sweden

What are the most significant challenges for people waiting for a new kidney?

One of the biggest challenges for many patients waiting for a new kidney is the strenuous long waiting time until a suitable transplant has been identified. This long uncertain wait is difficult for a lot of patients. Further, many of the patients on the transplant waiting lists have so-called donor-specific antibodies in the blood. The patients are not born with these antibodies but antibodies can develop through pregnancies, an earlier transplant or if the patient has received a blood transfusion. For these patients, the time on the transplant waitlist is even longer than for others, and some will not get transplanted before they have to be removed from the transplant waitlist because they become too sick to undergo surgery.

It is also challenging to stay healthy while waiting for transplantation. Renal disease patients have an increased risk of suffering from a number of co-morbidities including heart failure, infections, type 2 diabetes and other metabolic disorders.

How many Swedish patients are on dialysis today waiting for a new kidney and how does it look globally?

By the end of last year, nearly 700 kidney disease patients in Sweden were waiting for kidney transplantation, and the majority of these patients are currently undergoing dialysis. In Europe, about 50,000 patients are currently waiting for a kidney transplant. Waiting times can range from a few months to several years. In some cases patients never get transplanted because of the presence of donor-specific antibodies, or because they are too sick.

What makes it more difficult for some patients to find a suitable kidney?

When a kidney becomes available for transplant, the organ coordinator needs to look for a suitable recipient based on, for example waiting time and blood group. In addition, a so-called cross match test must be performed. In these in vitro tests (in the laboratory), you can see if the intended recipient has donor-specific antibodies. In order for the transplantation to take place, the patient should not have antibodies with the ability to bind to the transplanted kidney and cause irreversible damage. This means that the waiting time cannot strictly be used as a selection criterion, but it is also essential to map the recipient’s immune system so that the kidney has the best chance of being healthy and well-functioning for a long time.

Dr Stanley Jordan

Dr Stanley Jordan
Interview with Dr Stanley Jordan, Director, Nephrology & Transplant Immunology, Medical Director, Kidney Transplant Program at Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles and Professor of Pediatrics & Medicine, David Geffen School of Medicine at UCLA.

In the US, how many patients on dialysis are on the waiting list for a kidney transplant?

There are just over 114,000 patients on the transplant waiting-list right now. Of these, some 95,000 to 98,000 are waiting for a kidney.

In what way could fast depletion of IgG-antibodies improve the situation for patients waiting for a new kidney?

It would mean a breakthrough in transplantation of highly sensitized patients. These patients often have to wait a long period of time – about one third of the patients on the waitlist are moderately or highly sensitized. Many of them never get transplanted and these patients die while waiting for an organ.

How has the new Kidney Allocation System (KAS) implemented in 2014 improved the possibilities for transplantation for the highly sensitized patients?

It has definitely helped, we use the allocation system and it is a valuable complement.

However, the allocation system is great, but it does not solve the problem with matching for the highly sensitized patients. For those patients, desensitization still is the needed therapy.

Why is desensitization so important for kidney transplantation?

It is in fact a growing problem. Back when I started, and for many years – it was the general belief that the problem of sensitization would diminish over time.

It has not. For women, pregnancies are the major reason why they become sensitized. Another general reason is actually previous kidney transplantation. We lose about 5,000 kidneys a year – usually due to antibody-mediated rejection. Some 70% of these patients will be highly sensitized when they return to the waiting list. Patients also become highly sensitized due to other reasons such as following blood transfusions.

For me and my colleagues, antibodies are the problem “de jour”. The attention has definitely moved from the T-cells back to the antibodies. Fast IgG removal has the potential to enable more transplantations.

A short introduction to transplantation

Organ transplantation is a life-saving treatment where a failed organ is replaced with a donated organ from a living or deceased donor. In 2015, approximately 280,000 patients were on the transplant waitlists with around 200,000 waiting for a kidney. In 2015, approximately 44,000 kidney transplantations were performed in the US and Europe. Around 70 percent of the kidney transplantations were performed with kidneys from deceased donors. Around 9,000 patients died while waiting for a kidney transplant.

The alternative treatment for patients with failed kidneys is dialysis, a treatment that requires five–six hours of treatment three–four times per week which for most patients results in significantly impaired quality of life. Long-term dialysis is associated with risks of cardiovascular complications and death. Kidney transplantation in most cases enables patients to return to a normal life even though all transplanted patients need to be treated with immunosuppressive treatment.