Idogen recently announced that they have received approval from the Swedish Medical Products Agency for the clinical phase I/IIa study with IDO 8. The cell therapy is aimed at patients with severe haemophilia A who have developed antibodies to their substitution therapy with coagulation factor VIII. BioStock contacted Professor Jan Astermark, Principal Investigator in the clinical study, to find out more about the unmet medical need of these patients.
Idogen develops tolerogenic cell therapies to counteract the immune system’s unwanted activation. The ambition is to teach the immune system to tolerate the specific antigen that elicits unwanted activation.
The company’s lead candidate IDO 8 aims to create tolerance for coagulation factor VIII (FVIII) in patients with haemophilia A who have formed antibodies to their vital FVIII treatment to prevent and treat bleeding.
A large proportion of haemophilia A patients develop antibodies to their treatment
Haemophilia A is caused by a lack of FVIII, a glycoprotein needed for the blood to coagulate. Severe haemophilia A is usually treated every two or three days with an injection of factor concentrate containing the missing coagulation factor.
However, the immune system can recognise the substitution treatment as something foreign and harmful, which leads to that about a third of the patients develop inhibitory antibodies, so-called inhibitors, which inactivate FVIII and render the treatment ineffective. This means that patients no longer respond to FVIII treatment, which increases the tendency to bleed.
IDO 8 to enable treatment with FVIII again
Idogen wants to counteract this problem with the cell therapy IDO 8, which is intended to prevent the immune system from attacking FVIII, and thereby enable the patient to be treated with FVIII again.
The company plans to start a clinical phase I/II with IDO 8 during the second quarter of 2022. The Principal Investigator for the study will be Jan Astermark, Professor of Clinical Coagulation Medicine at Lund University, as well as Chief Physician and Head of the Coagulation Unit at the Skane University Hospital in Malmö.
Interview with Professor Jan Astermark
Professor Astermark’s many years of research have primarily been focused on hereditary bleeding disorders and how to optimize the treatment of haemophilia patients. He has been involved in the training of professionals worldwide and has a wide, international network of contacts in the field.
In the below interview with BioStock, Jan Astermark talks more about the standard treatment for haemophilia A today and why there is a need for new drugs.
Jan, first of all, what is haemophilia A?
– Haemophilia A is the most common form of haemophilia and is due to a congenital deficiency of factor VIII (FVIII), which is a protein that is needed to stop bleeding if, for example, you injure yourself. Patients have either a total absence of FVIII or a partial deficiency of FVIII. The disease is therefore divided into mild, moderate and severe haemophilia A.
How do you treat haemophilia A today?
– Patients with severe haemophilia A have an immeasurable level of FVIII and are treated preventively with intravenous injections of FVIII preparations, so-called factor concentrates. The treatment starts at the age of one year and is given about once a week in the beginning, and then increases to about every other day. The FVIII treatment creates good protection against bleeding and prevents joint injuries that are otherwise a major problem in these patients. Without preventive treatment with FVIII, there is a high risk of deformed joints and severe bleeding.
Many patients develop inhibitory antibodies to FVIII. How extensive would you say this problem is?
– If the body has never seen the coagulation factor before, it is not that unexpected that the immune system can react by producing antibodies to the factor concentrate fairly quickly after starting the treatment. The antibodies counteract the effect of FVIII, which means that the treatment no longer works. This is noticeable when the patient suddenly begins to bleed abnormally. The treatment thus no longer has a haemostatic effect.
– Unfortunately, antibodies to FVIII are a fairly common problem affecting about one-third of patients with severe haemophilia A.
»Unfortunately, antibodies to FVIII are a fairly common problem affecting about one-third of patients with severe haemophilia A.«
Patients with antibodies are treated with an intensified treatment with FVIII to induce tolerance, which is also called Immune Tolerance Induction (ITI). Could you tell us a little more about this?
– With the help of immune tolerance treatment, an attempt is made to get rid of the antibodies. The patients are often treated with relatively high doses of the FVIII preparation for a longer period, up to several years, to “exhaust” the immune system. In about two-thirds of cases, this succeeds and the patient becomes tolerant, while the remaining third have to live with antibodies that prevent them from being treated with FVIII.
– The immune tolerance treatment can be very stressful for both the child and the family because you usually give daily doses of a lot of factor concentrate. A port-a-cath or the like may be needed to provide the treatment. As if that was not enough, the child also has an increased risk of bleeding.
Are there other treatment options for patients with FVIII inhibitory antibodies?
– There are currently a few other treatment options that can improve the situation for haemophilia A patients who do not get rid of their antibodies. For example, bleeding can be treated with recombinant factor VIIa, which is a so-called bypass product. The treatment can also be given for preventive purposes but is not as effective as FVIII in this respect. Then there is Hemlibra, a relatively new drug that contains an antibody that has been developed to function as FVIII. The advantage of Hemlibra is that it is given subcutaneously about once a week, instead of injections into the vessels several times a week.
– However, none of these treatment options provides adequate protection against bleeding. Should the patient undergo surgery or be seriously injured, additional medication must be added. Basically, factor concentrate is the best treatment because it contains the protein that the patient lacks.
– Since haemophilia A is a genetic disease, it is also conceivable that some of the patients could be treated with gene therapy, which is under development today.
What drives doctors to participate in clinical trials with new drugs in haemophilia?
– There is definitely a great need to make patients tolerant to the treatment that contains the protein they lack and need, i.e. FVIII.
– We in healthcare always wants to have the patient’s best interest at heart. I want to be able to offer all my haemophilia A patients, including those with antibodies to FVIII, the best possible treatment. Therefore, I choose to participate in research and clinical trials in the field.
What do you think is particularly interesting about Idogen’s development of cell therapy to treat antibodies to FVIII?
– Idogen is developing a treatment with a completely new mechanism for creating tolerance to FVIII in patients with haemophilia A. Research on why and how the immune system produces antibodies to FVIII and what can be done to counteract this has been going on for a long time. Idogen uses the knowledge about which regulatory molecules and cells that are involved in the immune response to be able to reset the immune system so that it does not react to the factor concentrate.
What effect do you want to achieve with IDO 8?
– Idogen’s cell therapy is aimed at haemophilia A patients who have difficulty getting rid of their antibodies to FVIII with immune tolerance therapy. It would be extremely valuable if we could succeed in making these patients tolerant to FVIII. Then you would be sure that treatment with FVIII provides effective protection against bleeding and that the effect of FVIII is easy to measure when the patient is bleeding or needs surgery.
– In the upcoming clinical phase I/II study with IDO 8, which is a First-in-Human study, we want to see that the treatment quenches the immune response to FVIII and that the antibody reaction disappears. The goal is for IDO 8 to enable the immune system to accept FVIII so that the patient can once again be treated with factor concentrate.
»I do not know of any other company, or research group, that uses the same technology as Idogen, so it will be extremely exciting to be a part of their development.«
What is the interest in research and development in haemophilia A?
– Haemophilia is a relatively costly disease for society that in many cases has a significant impact on patients’ life situation. There is, therefore, a great socio-economic interest in optimising the treatment and counteracting injuries and bleeding in these patients.
– In general, there is great interest in research and development of new treatments in the area. I do not know of any other company, or research group, that uses the same technology as Idogen, so it will be extremely exciting to be a part of their development.The content of BioStock’s news and analyses is independent but the work of BioStock is to a certain degree financed by life science companies. The above article concerns a company from which BioStock has received financing.