Rare Disease Report

Peter Turecek, PhD, Explains How Medical Devices May Benefit Patients with Hemophilia

DECEMBER 13, 2018
Krista Rossi
Hemophilia A is a rare blood disease characterized by prolonged bleeds due to abnormal blood clotting. While prophylactic treatment can benefit some patients, a team of investigators have found that integrating FVIII pharmacokinetics can help create an individualized treatment.

At the 60th ASH Annual Meeting & Exposition in San Diego, California, Peter Turecek, PhD, senior director of Global Medical Affairs at Shire, sat down with Rare Disease Report®(RDR®) to discuss new strides being with Irish Personalized Approach to the Treatment of Hemophilia (iPATH), which is evaluating how an early prophylaxis in combination with an assistant device like myPKFit can improve the outcomes of treatment.

[Editor’s note: Transcript is slightly modified for readability.]

RDR®: What is the background behind this trial? 

Turecek: “For the first time, we are presenting results from the iPATH study, which was initiated in Ireland. The principal investigator is James O'Donnell, MD, PhD. He's a professor at the Trinity College, and he's also heading the largest hemophilia Centre in Ireland.

He and his colleagues are identifying markers for hemophilic patients in order to answer some of the basic biochemistry and biology questions related to coagulation factor VIII.  

The essence of the study that will run for 4 years is to identify some of the underlying principles for variables of outcomes of treatments. There are some unanswered questions for hemophilic patients because even though many of them are treated with prophylaxis with coagulation factor VIII, the outcomes are quite different. Some patients develop inhibitory antibodies, others do not. Some patients develop joint disease, others do not. Some have short half-lives of a coagulation factor, others have longer half-lives.

We want understand why this is the case, and so for the first time, [this study] tries to attempt to correlate some of the variables of treatment outcomes with underlying markers. Ireland gives a specific opportunity here because there is a closed cohort of hemophilic patients. They are all controlled by a small number of centers, so it's easy for them to collaborate and identify the commonalities and discrepancies between patients.

They do all this based on myPKFit, which is a medical device that is part of our telemedicine program. It includes input from the patient, which is done by the doctors who are providing care for the patients' input, like what form of hemophilia they have, what kind of treatment they get, personal numbers like body weight, age, blood group—which is also an important variable for pharmacokinetics. All these data together go into a system, which then calculates the pharmacokinetics based on the so-called population pharmacokinetic models.

At Shire, we have established pharmacokinetic models for 2 of our products. One is ADVATE, and the other is ADYNOVATE. These are based on the clinical trial data of these 2 products with respect to pharmacokinetics. By only taking 2 blood draws from the patients, the tools give patients and physicians—based on the population pharmacokinetics—a PK curve, which tells the patient where he stands with his factor level after he received a dose

Usually, a pharmacokinetic requires 10 to 12 plot rows; in this case, it requires only 2.  

The physician is also capable of correlating the prescription with the outcome of the patient by looking in a telemedicine approach to the treatment-related numbers, whatever that is.

The iPass study incorporates myPKFit into the investigation of the variables of treatment outcomes of hemophilic patients.

The main conclusions from the study that we are presenting here is that the blood group determines half-life effect rate—that is something that is also not new, but it's new based on the myPKFit modeling, which is much easier than previous determinations of pharmacokinetics. They are looking into bleeding rates, which are dependent on the factor levels found in in patients, of course.

Shire is also investigating this in a clinical study that is called the PROPEL study. We will present data on this early next year. That is a study that is aiming to look systematically into what the outcomes will be in patients having trough levels—that is the lowest level of a grade that is obtained upon regular prophylaxis with levels between 8% and 12%. Current trough levels in regular treatment regimes are 1% or maybe 3%, but here we have a study where we go up to 10%. We'll see how the outcomes are changed when you go to higher trough levels. It's also something that the Irish team will look into further based on the models and markers they have.”  

RDR®: What are the next steps with this data?

Turecek: “The patient cohort in Ireland is based on a national registry, so investigators know all their hemophilic patients in the country. That may be especially easy in the island situation that Ireland has.

Now, investigators have data from all the patients that have been treated with 1 certain product, which is ADVATE. It is the recombinant protein-free manufactured factor VIII product that is available in many countries in the world, including Ireland.

The patients had been recruited to this study, and now the next steps will be to work on certain so-called work packages, which are follow-up investigations on those patients. One is targeting to go for identifying biochemical markers for inhibitor development. The other would be to identify some biochemical, biological markers for the pharmacokinetics. These are done by groups in Ireland, but they are also all supported by scientists from Shire.

We have joint sub projects we where we meet regularly and discuss the results. That is the next phase. The study is now running for a little bit more than a year, so we have another 3 years ahead of us. In addition to the established study in Ireland, we are also looking into a globalization of the study because it should be open also to other centers to participate.

One thing that is also part of the plan is to have full genomic data from the patients. We will get sequence analysis from their genome that will be done in Ireland and likely in collaboration with the US National Institute of Health (NIH).

The implications of the data suggest that implementation of an early prophylaxis in combination with an assistant device like myPKFit improves the outcomes of treatment. While this is something that had been at least theoretically recognized, there is a first set of data that will give objective clinical results that will help to verify what has been a hypothesis for many years."

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