Interview with Dr Jens Kjeldsen-Kragh MD PhD
(Story by Becky Robinson)
We are excited to announce that Naitbabies have been asked to join the Sounding Board for Prophylix Pharma AS (PPAS) which also includes Professor Dick Oepkes, Professor Stanislaw Urbaniak and Professor James B Bussell. PROFNAIT is a collaborative project aiming to develop the first drug that will be able to prevent severe bleeding in foetuses and newborns due to foetal/neonatal alloimmune thrombocytopenia (FNAIT). The project will establish the scientific, clinical and quality documentation that is required to obtain Marketing Authorization in the EU for the new drug. In addition to Prophylix the project includes 8 consortium partners within Norway, Sweden, Denmark and Germany.
Dr. Jens Kjeldsen-Kragh is the Chief Scientific Officer at Prophylix Pharma, and he was kind enough to take some time out of his very busy schedule to talk to me about himself, his work and the very exciting PROFNAIT project.
Dr. Kjeldsen-Kragh is a specialist in Immunology and Transfusion Medicine and has been involved in research on blood platelets for more than a decade. In 2000 Dr. Kjeldsen-Kragh and colleagues at the University Hospital of North Norway in Tromsø planned a very large prospective observational trial of HPA 1a-negative women – the largest prospective study of FNAIT ever performed. More than 100,000 pregnant women were HPA 1 typed, and those who were HPA 1a-negative (2.1%) were screened for anti-HPA 1a (10.6% of these). The pregnancies of the HPA 1a-negative women were followed and the mother’s antibody levels were tested at regular intervals. The study found that the majority of women are immunised against HPA-1a after delivery of their baby. This is similar to the situation that occurs in haemolytic disease of the newborn (HDN) where a RhD negative woman gives birth to a RhD positive child. With HDN, during birth, the mother may be exposed to the infant’s blood, and this causes the development of antibodies, which may affect the health of an RhD positive foetus in subsequent pregnancies. Today RhD negative mothers who have given birth to an RhD positive child are given an injection of anti-RhD immunoglobulin (commonly known as anti-D) to reduce the risk of any subsequent babies being affected by maternal antibodies against RhD. Dr. Kjeldsen-Kragh and his collaborators in Tromsø began researching the possibility of using the same approach against HPA-1a.
Together with researchers in Toronto, Canada, the Norwegian team made a proof-of-concept study in a mouse model of FNAIT. The study proved that, conceptually, a prophylactic administration of platelet antibodies leads to suppression of antibody production and prevents poor pregnancy outcome in FNAIT. (A prophylactic drug is one that is used to prevent a disease, rather than to treat or cure a disease).
The next stage in the process, following on from the mouse study, was to develop a prophylactic drug to be used on humans. As FNAIT is classified as a rare condition, Prophylix Pharma was granted ‘Orphan Drug Designation’ for their prophylactic drug by the European Medicines Agency. Benefits and privileges are associated with Orphan Drug Designation and is used to encourage pharmaceutical companies to develop medicinal products for rare conditions, as otherwise it would not be cost effective for companies to do so. Obtaining this designation was a huge breakthrough and meant it was possible for Prophylix Pharma to apply to the EU Commission for a grant of €6m in order to develop the drug. They received a very favourable evaluation from the commission and are currently in the final negotiations to obtain the grant.
PPAS along with the consortium members are now in a position to begin the massive task of collecting blood plasma from hundreds of women who have antibodies against HPA-1a. Immunoglobulin G needs to be extracted from the donated blood plasma and purified to produce the drug. 2,000 litres of blood plasma is required at this stage of the procedure. Once enough plasma has been collected, the human testing (phases I and II) will begin. This will take place at the University of Tromsø. The purpose of the phase I/II trial is to determine the level of dosage that will be used and to assess if there is any toxicity associated with the drug. Dr Kjeldsen-Kragh stated they don’t believe there will be any toxicity issues as the drug is so similar to that used for HDN – the only difference being the specificity of the antibody used in the drug – in this case platelet antibodies. This stage of trials is required for all medications.
The final phase (phase III) of the testing will involve screening 75,000 pregnant women to ascertain their platelet type. From this sample of 75,000 it is expected that 2% will be HPA 1a-negative. Those that have not developed antibodies during the pregnancy will be used in the trial. These approximately 1,500 women will be split into two groups. Shortly after giving birth to an HPA 1a-positive child, one group will receive the prophylactic treatment, and the other group will receive a placebo. This will be a double blind study, so neither the women participating in the trial, nor the researchers will know who has been administered with the prophylactic. All of the mothers will be tested several times during a year after delivery to establish whether antibodies have developed following giving birth. The results from both of the groups will be tested and compared. If there is a significant difference in the two groups then this will be formal proof that the drug is effective. Once all the relevant paperwork and approvals have gone through following the trials, then the drug can go to market.
The donation and collection of blood plasma is a big challenge for the team. They need as many women as possible who have antibodies against HPA-1a to sign up and register their interest in assisting the project. While the project is based in Europe, Dr Kjeldsen-Kragh has asked for women all over the world to sign up and register their information so they can be contacted should the collection of plasma be required from elsewhere.
Plasma is collected by a special procedure called plasmapheresis. Blood is collected the same way as in a normal blood donation, but during plasmapheresis a special piece of equipment – the apheresis machine – is used to separate plasma from the blood by centrifugation while returning the blood cells (red cells, white cells and blood platelets) to the donor. In other words, you will keep all of your valuable blood cells and only the plasma will be collected. It is usual to collect around 600 ml plasma in one procedure which takes from 30 to 60 min. Donors can safely give blood plasma one or two times a month.
If you would like to help, please go to http://www.prophylixpharma.com/donate-plasma/.