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Recent Advances in the Treatment of Hereditary ATTR Amyloidosis (hATTR) - Episode 14

Evaluating the Potential of Vultrisiran

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Expert discussion on the recent topline results released for vutrisiran in the HELIOS-A trial.

John L. Berk, MD: There has been some exciting top of the line results shared by Alnylam Pharmaceuticals, Inc on a study named HELIOS-A looking at a drug called vutrisiran, which is a second-generation TTR gene silencer. There is hope for it to be the new and improved patisiran. Dr Brannagan, what were your thoughts about the press release for vutrisiran?

Thomas H. Brannagan III, MD: It seemed like exciting data; I would like to see more of it, but at 9 months there was already a difference between the placebo arm and the active drug. This was true of patisiran as well as inotersen. They also reported that there was a very good safety profile. It was thought at the time of the study that is was unethical to have a placebo arm, therefor the study compared the drug to the historical placebo from the patisiran APOLLO study. However, there was an active comparator arm with patisiran, and I did not see data in the press release about how the new drug compared to patisiran; I would be interested in that.

John L. Berk, MD: Dr Polydefkis, let’s say you’ve got patients who are on patisiran and they’re getting intravenous infusions every 3 weeks. Vutrisiran sails along and meets FDA approval; what’s the future for your patients on patisiran?

Michael J. Polydefkis, MD: First, we’ve been a little bit spoiled. Here’s this terrible progressive disease, and we have yet another drug that I would characterize as another grand slam. We’re becoming spoiled with all this success. The data that were announced are not complete, but it does look remarkable. The difference at 9 months was on par with what we see in the APOLLO-B study; it looks very similar. Would I switch patients? Again, I think it’s a discussion with the patient. However, the once every 3 months subQ [subcutaneous] injection does sounds better than an infusion every 3 weeks.

John L. Berk, MD: Reported were quality of life, gait speed, and the neuropathic measures. Dr Witteles, I’m really going to stretch you on this one. There was a mention in the press release that NT-proBNP [N-terminal pro-B-type natriuretic peptide] improved, or that there was movement in an improving direction. Is that surprising to you? How does that fit with your concepts of TTR protein stabilization with tafamidis?

Ronald Witteles, MD: It’s certainly not surprising in the context that patisiran clearly did that in the APOLLO trial. In the APOLLO trial they had a subset of patients who had clear evidence of cardiac involvement who were preidentified. On average in the placebo arm, their NT-proBNP went from about 700 to 1100 [pg/mL]. In the patisiran arm, it went from about 700 to 600 [pg/mL]. Frankly, it would have been surprising just based on mechanism if the vutrisiran showed anything different. In the cardiac world, there are phase 3 studies with vutrisiran as well as the next-generation form of inotersen going on as we speak. I believe all of us are extremely excited about their potential for the cardiac form of the disease based on how the disease works; it would be shocking if they weren’t effective

John L. Berk, MD: Thank you for watching this NeurologyLive® Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox.

Transcript Edited for Clarity