Assessing the Primary Results of ATTRibute-CM

In part two of a three-part interview, CardioNerds Academy Fellow Anna Radakrishnan, MD, MBA, of The Mount Sinai Hospital, speaks with Daniel Judge, MD, of Medical University of South Carolina. Dr. Judge breaks details and interprets the primary findings of the ATTRibute-CM trial, which favored acoramidis over placebo across mortality, hospitalization, and functional measures in the treatment of ATTR-CM.

Transcript:

Ana Radakrishnan: How would you say clinicians should really interpret these findings in the context of their clinical practice? And what would you say are the potential implications for the future therapeutic strategies in the management of ATTR cardiomyopathy?

Daniel Judge: Well, one thing that I should mention, because, since the last time I spoke with you. and the recent data coming out of [the] FDA is the approval of a third drug now for ATTR cardiomyopathy. So we have Tafamidis, which has been around since 2019, now Acoramidis since November, and Vutriceran recently with expanded access. So as a clinician taking care of patients with heart failure from cardiomyopathy, it’s no longer easy for me to say, well, you’re on the only drug that works, and who cares if it’s working or not? We don’t need to know because we don’t have any good ways of doing it.

Now, the impact, back to clinicians, what does this mean? It means you’re responsible for seeing how are they doing on Tafamidis, if that’s the drug or if you use something else. We’re in a new position, in a new era of taking care of patients with this disease. Is the therapy you’re doing working? Is the patient getting worse? And what is the next option? What else do you have? And you have more tools in your toolbox, more drugs to prescribe for this condition. So I think it’s a really new era and it provides more burden or more responsibility on the clinicians caring for these patients.

Ana Radakrishnan: And as we enter into that era with the multiple commercially available treatments, how should future clinical trials be designed to ensure both scientific rigor and real world relevance for clinicians?

Daniel Judge: Well, I think, as I said earlier, this is probably the last placebo controlled trial that we’ll ever see for ATTR cardiomyopathy. And I’m excited that two trials really are going to answer the question. And I think one important question that we didn’t really talk too much about is the idea of turning off the gene or depressing the level of TTR production versus stabilizing the TTR complex. Both of them have proven safety and efficacy for treatment of ATTR cardiomyopathy or neuropathy in both cases. So we’re back to the question of which is the better strategy? Is there a benefit of combined therapies? Is one or the other better than… Is either strategy better?

So two trials will answer that question. The CARDIO-TTRansform trial, we’ll see results in about a year. We’re excited about that. It’s the largest study with over 1400 people enrolled and a larger number of people taking Tafamidis, randomized to Eplontersen, which is a TTR knockdown therapy.

And I’m excited about a trial that’s coming along, the TRITON trial which is Alnylam’s Nucresiran, a next generation TTR knockdown therapy that we believe will be more potent, hopefully. And everyone in that trial will be on a TTR stabilizer. So we’ll have the ability to compare the two in the same study. And I think that the future, and the near future, we’re going to have some better answers to that question.

Ana Radakrishnan: Awesome! Well, thank you so much Dr. Judge for sharing your insights and for your continued leadership in advancing the care of our patients with transthyretin cardiac amyloidosis. It’s been an absolute pleasure speaking with you as usual, and thank you once again for your time.

Daniel Judge: Well, thank you, Ana. [I] appreciate it.