FDA Approval of PiaSky for Pediatric Patients with PNH | Aplastic Anemia and MDS International Foundation (AAMDSIF) Return to top.

FDA Approval of PiaSky for Pediatric Patients with PNH


Leigh Clark:    Welcome. Hi, welcome to Podcasts for Patients. My name is Lee Clark, Director of Patient Services, and I will be moderating the podcast today. Before we get started, I'd like to thank our corporate sponsors and our diamond sponsors, Novartis and Alexion, and the patients and families who support our organization. Without your support, our podcast would not be available. So, today I have the pleasure of speaking with Dr. Satheesh Chonat, who is with Atlanta Children's, in Atlanta, Georgia. And we're going to be talking about the recent approval of PiaSky for pediatric patients. Welcome. Thank you so much for joining me today.
Satheesh Chonat:    Thank you so much for having me. It's a, it's such a pleasure.
Leigh Clark:    So, what is PiaSky?
Satheesh Chonat:    Yeah. So PiaSky is a, a brand name or commercial name for a drug called Crovalimab. Crovalimab is new in class, anti-complement C5 antibody. So it's a novel antibody that just recently got approved by FDA  for patients with PNH. It's currently approved for adults and children over 13 years of age, weighing over 40 kilograms of body weight.
Leigh Clark:    How is it given and what do we know about side effects?
Satheesh Chonat:    So Crovalimab as a medication is highly soluble, so that has helped for it to be allowed for a low volume subcutaneous injection. So injection that's given typically just under the skin, and it's given every four weeks as a maintenance dosing, so children, adults have to get a few weeks of loading doses. The very first is given intravenously and subsequent ones are given subcutaneously, because it can be given or administered subcutaneously, it can be self-administered at home.
    Answering your second part of the question, what are the known side effects? PiaSky has been studied across three phase 3 clinical trials in patients with PNH. So the pooled safety data, putting them all together, the overall safety profile of Crovalimab, or PiaSky, has been shown to be similar to Eculizumab, which is the other medication commonly used for PNH. And the rates of adverse events, comparable between,  the populations.
    But it's important to recognize that all complement inhibitors carry, a class risk of infections, meaning, especially the infections with encapsulated bacteria. The ones that we talk about most are, a risk with meningococcal infections, due to how the complement blocks the body's ability to fight such infections. There were no occurrences of meningococcal infections, reported in any of these studies. Other common adverse events that occurred in small proportion of patients receiving Crovalimab included, pneumonia, respiratory tract infections, viral infections such as COVID-19, low platelet count, and other infusion related reactions. So reactions secondary to the medicine given, subcutaneously.
    Another unique side effect that's important to remember for patients and providers, that were noted in the clinical trials, were these transient immune complex reactions. So these are hypersensitivity reactions, and they were only seen in those patients who switched between Crovalimab and other C5 inhibitors, such as Eculizumab or Ravulizumab. So prescribers need to be aware of this reaction and be cautious when a patient switched either to Crovalimab or Crovalimab to another C5 inhibitor.
Leigh Clark:    Thank you. Can you tell us about the clinical trial that led to the approval?
Satheesh Chonat:    Yeah. Excellent question. So Crovalimab, as mentioned earlier, was studied across three phase 3 clinical trials in patients with PNH. Um, so they pulled all the data from about 377 patients with PNH, treated with Crovalimab, across these three clinical trials. And that's what led to this FDA approval. So the three studies were called COMMODORE, 1, 2, and 3. In COMMODORE 1, they selected patients who have previously been receiving,  C5 inhibitors such as Eculizumab, and they randomized those patients to receive either Crovalimab or continue on their C5 inhibitor Eculizumab. And there were about 45 patients who received Crovalimab in this study.
    In COMMODORE 2, which is one of the primary studies which led to the FDA approval, they selected patients who had never been treated with C5 inhibitor. So they called a C5 inhibitor-naive patients. They were randomized to receive Crovalimab or Eculizumab, in a ratio of 2:1. And, then, they offered those patients who were not initially randomized to receive Crovalimab, they could switch to Crovalimab after the initial 25 weeks of treatment.
    The COMMODORE 3 is another study, which was a non-randomized study, meaning the patients where, they knew what drug they were getting, and they were for all patients who had never been treated with C5 inhibitor and they received Crovalimab only. So in combination, these three clinical trials helped its approval, because these studies helped demonstrate the efficacy of Crovalimab in blocking the complement mediated hemolysis or the breakdown of red blood cells, and it was shown to be non-inferior to Eculizumab.
Leigh Clark:    What is the difference between, PiaSky and Ultomiris?
Satheesh Chonat:    Yeah. Another excellent question. So both are complement C5 inhibitors, but they actually act on different spots on the C5 molecule. It's important to note there are no head-to-head clinical studies comparing PiaSky and Ultomiris. Both of these are FDA approved for children. Crovalimab is approved for those over 13 years of age and weighing 40 kilograms or more. Ultomiris is approved for all ages and children one month and older, but the PiaSky is given every four weeks, once they're on maintenance dosing, while the Ultomiris is given every eight weeks, unless the child is, under 20 kilograms when, which requires Ultomiris to be given every four weeks.
    So, as I mentioned earlier, PiaSky is given just under the skin. So that's an important difference. So it's given what I suppose is, administered as a subcutaneous injection, so that certainly has a risk of leading to some injection or infusion related side effects. Ultomiris requires an IV line to be placed, because it's always given intravenously. But both can be administered at home, depending upon what's available based on your insurance, et cetera. It's important to monitor patients switching from C5 inhibitor, to PiaSky or from PiaSky to another, as they're at risk for type three hypersensitivity reactions, especially the first few weeks after starting this medication. These are the major differences between PiaSky and Ultomiris.
Leigh Clark:    What else is important for parents to know?
Satheesh Chonat:    Yeah. Excellent. So, in addition to understanding that these are, the PiaSky and Ultomiris or other, Eculizumab, are common use medications for pediatric patients with PNH. It's important to remember that PiaSky is a new drug, but it's definitely studied and is shown to be non-inferior to Eculizumab. In several studies, as mentioned earlier. The efficacy of Crovalimab or PiaSky and the side effects of PiaSky are comparable to Eculizumab. I'm mentioning Eculizumab, even though it's not officially approved for children with, PNH. That's because there’s no head-to-head studies comparing PiaSky to Ultomiris, which is the only other approved medication for children with PNH.
    So, the families out there who are interested in learning more about PiaSky, please reach out to your provider treating PNH, especially if you're 13 and older. Or you could reach out to one of the AAMDS recognized centers, treating children with PNH, and we can happily discuss, the eligibility criteria, et cetera.
Leigh Clark:    Cool. Thank you so much for sharing your time and your expertise with all of us, and learning about the new treatment option available to parents and to physicians. This is an exciting time for families with their loved ones who have been impacted by PNH. If you'd like to learn more about the new treatments, please do visit our website, which is AAMDS.org, or give us a call at (800) 747-2820. Thank you again so much for joining us today. We really appreciate you sharing your time.
Satheesh Chonat:    Thank you.