VIDEO RESOURCE

Shawn: Hello everyone. My name is Shawn Streeter. Today we're going to be discussing a case of pediatric immune thrombocytopenia. I have with me here today Doctor Michael Tarantino. Doctor Tarantino, would you like to introduce yourself?

Dr Tarantino: Thank you, Shawn, and thank you for inviting me here. As you said, my name is Michael Tarantino. I'm a physician, and I'm the CEO and chief medical officer at the Bleeding and Clotting Disorders Institute in Peoria, Illinois. I've been a hematologist for over 30 years. I've been a student and a studier of ITP for that long, if not longer. And I'm really excited to have a discussion with you about a particular patient, but also about ITP in general.

Shawn: Yeah. Thank you for being here with us today. So let's go ahead and get right into it. So could you tell us a little bit more about this patient? How did they present at diagnosis of ITP?

Dr Tarantino: So this was a 15-year-old young man, very nice kid. And he had what you would call sort of a familiar or typical presentation for ITP. He suddenly had acute bouts of bleeding symptoms, primarily mucocutaneous symptoms. It was a lot of nosebleeds at the time. His ITP was diagnosed, and he received initial therapy with immunoglobulin or IVIG and responded very briefly, but didn't have a durable response to that. So thereafter, a typical next step at that time was to start corticosteroids. And again, this had a temporary effect, but not a lasting effect. But in addition to that, it caused some steroid-like symptoms that were a problem of obesity, cushingoid symptoms, sleep disturbance, mood changes that were really limiting really caused a problem. So those so those effects prompted the decision, the decision to switch off of corticosteroids. Unfortunately the other things that were tried by his haematologist included Anti-D therapy, rituximab, no durable response with either treatment. And before coming to see us at the Bleeding and Clotting Disorders Institute, he was switched to Eltrombopag.

Shawn: Got it, So it sounds like this patient tried quite a few options. So when the patient eventually was referred to you and presented to your clinic, what was your first strategy?

Dr Tarantino: Well, the patient had already started on Eltrombopag and it didn't seem to be working well. So we certainly continued the therapy but went over some things that are particular to that agent, including the dietary restrictions associated with it. They were unaware of the dietary restrictions, but when we went through the requirements, if he were to continue on Eltrombopag the patient was a little reluctant to agree to those dietary restrictions. We tried it anyways, and sure enough, things didn't work and he really had almost no effect from the Eltrombopag but admitted that he was eating before the restriction. Time had come about, and we knew at that time that was influencing or having a negative impact on the efficacy of eltrombopag at that time.

Shawn: Right. So this patient has tried quite a few therapeutic options already, namely IVIG, rituximab, Anti-D, Eltrombopag. What was the next step for this patient? What was trialled afterwards?

Dr Tarantino: Well we tried a different TPO-RA that's Thrombopoietin receptor agonist. This one was Romiplostim. Again, even though that's a once a week subcu medicine, we found it very difficult to achieve a stable platelet count despite titrating the drug according to the manufacturer's recommendations. So we did find that the patient really was not being completely adherent to the prescription so he would miss doses. The family did some travelling. Around this time, and they found it very cumbersome, if not limiting, to be on a schedule of every week. So it made it difficult to stick with romiplostim. And we had to have another choice.

Shawn: Sure. And so it sounds like compliance might have been an issue with Eltrombopag and Romiplostim. Um, what was what was your next strategy for this patient after the Romiplostim? Seemed like it wasn't going to do the trick.

[00:04:33] Dr Tarantino: Well, we really wanted to stay with a TPO-RA, and our only other choice at that time was to try Doptelet.

[00:04:42] Shawn: Sure.

[00:04:43] Dr Tarantino: Um we knew that there isn't a dietary restriction. In fact, it encouragement to take Doptelet with food. And this, uh, particular patient found that to be actually reassuring because of his dietary habits. So at that point he was started on Doptelet and he was adult sized at the time. Uh, so we use the typical starting dose for Doptelet and really he uh, at that time he was adherent to the treatment and had a very good response. Platelet count very quickly went to around 100,000, and he was having a good experience with Doptelet.

[00:11:23] Shawn: Yeah. And overall, how is the patient doing recently while on the Avatrombopag?

[00:11:27] Dr Tarantino: Well, again, we found that when he takes the medicine as prescribed, he does very well. And he really, you know, is able to sustainably keep his platelet count above 100,000, for example. And at that platelet count, he really doesn't have any bleeding symptoms. So he's very pleased. Unfortunately, occasionally he does lapse from the program. And there was a period of time, for example, where he missed several doses of Doptelet his platelet count did drop, and he did have to receive rescue therapy because he did have not only a low platelet count, but some bleeding symptoms. But since that time, I think with some counselling about the importance of adherence, he's been able to keep his platelet count in a safe range.

Shawn: That's great. I'm glad he's doing well and I'm sure our audience is glad he's doing well as well. So any closing thoughts or take home messages that you'd like to share?

Dr Tarantino: Well, I think that the our patient that we described here is a great example of how we need to personalise care for every patient. We're in that era of precision and personalised medicine. So obviously it took a little bit of searching and experimentation, but we certainly found that Doptelet was a very good choice for him. He really hasn't had any reported side effects that he's told us about, and he admits and knows that he, he should stick with the program in order for the regimen to work. Um, but I guess the take home point is that monitoring adherence, uh, for your patients is ultimately important and really stress upon the patient, not just the onus of taking the drug when it's supposed to be taken and at the dose prescribed, but really making it a part of their daily routine, if not their life routine, to take the medicine as prescribed.

Shawn: Right.

Shawn: Thank you, Doctor Tarantino. I appreciate your time and thanks for being with us here today.

Dr Tarantino: No thank you. My pleasure.

INDICATION

DOPTELET is indicated for the treatment of:

• Thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment
• Thrombocytopenia in pediatric patients 1 year and older with persistent or chronic immune thrombocytopenia who have had an insufficient response to a previous treatment

IMPORTANT SAFETY INFORMATION

WARNINGS and PRECAUTIONS

Thrombotic/Thromboembolic Complications

DOPTELET has been associated with thrombotic and thromboembolic complications in patients with ITP. In adult patients with chronic immune thrombocytopenia, thromboembolic events (arterial or venous) occurred in 7% (9/128) of patients receiving DOPTELET. Consider the potential increased thrombotic risk when administering DOPTELET to patients with known risk factors for thromboembolism, including genetic prothrombotic conditions and acquired risk factors.

DOPTELET should not be administered to patients with ITP in an attempt to normalize platelet counts. Monitor platelet counts and follow the dosing guidelines to achieve target platelet counts. Monitor patients receiving DOPTELET for signs and symptoms of thromboembolic events and institute treatment promptly.

DRUG INTERACTIONS

Moderate or Strong Dual CYP2C9 and CYP3A4 Inducers or Inhibitors

Concomitant use of DOPTELET or DOPTELET Sprinkle with a moderate or strong dual inhibitor or inducer of CYP2C9 and CYP3A4 may increase the risk of DOPTELET or DOPTELET Sprinkle toxicities or reduce DOPTELET or DOPTELET Sprinkle efficacy.

ADVERSE REACTIONS

Adult ITP

The most common serious adverse reaction was headache.

The most common adverse reactions (≥10%) were headache, fatigue, contusion, epistaxis, upper respiratory tract infection, arthralgia, gingival bleeding, petechiae, and nasopharyngitis.

Pediatric ITP

The most common serious adverse reactions were thrombocytosis and headache.

The most common adverse reactions (≥10%) were viral infection, nasopharyngitis, cough, pyrexia, and oropharyngeal pain.

USE IN SPECIFIC POPULATIONS

DOPTELET may cause fetal harm when administered to a pregnant woman.

Breastfeeding is not recommended during treatment with DOPTELET and for at least 2 weeks after the last dose.

These are not all the possible risks associated with DOPTELET. Please see Full Prescribing Information for DOPTELET and DOPTELET Sprinkle.

To report suspected adverse reactions, contact Sobi North America at 1-866-773-5274 or FDA at 1-800-FDA-1088.