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Five Things to Know about TRITON-CM & How Community Insight is Shaping the Future of ATTR-CM Research
March 27, 2026
In recognition of Amyloidosis Awareness Month, we’re spotlighting how listening to patients and clinicians helped shape the design of the TRITON-CM clinical trial.
At Alnylam, advancing innovation in RNAi therapeutics means more than developing new medicines, it means designing clinical trials that reflect the real-world experiences of the people that the medicines are intended to help.
TRITON-CM, our Phase 3 clinical trial evaluating nucresiran, a third-generation investigational RNAi therapeutic for transthyretin amyloidosis with cardiomyopathy (ATTR-CM), represents one of the largest global studies ever conducted in this disease. But beyond its scale, TRITON-CM also reflects something equally important: what we learned from listening.
At Alnylam, innovation extends beyond our RNAi therapeutics – it includes how we design the studies that evaluate them. TRITON-CM demonstrates how integrating community feedback and scientific evidence can lead to more thoughtful, inclusive clinical research that advances care for patients worldwide.” – Carol Pitcher-Towner, Senior Vice President, Head of Pipeline Delivery at Alnylam Pharmaceuticals
Here are five things to know about TRITON-CM clinical trial.
1. TRITON-CM is one of the largest global ATTR-CM trials to date
TRITON-CM aims to include approximately 280 sites across 38 countries, reflecting a commitment to enroll a broad and diverse patient population. As awareness of ATTR-CM continues to grow, it is critical that clinical research reflects the global nature of the disease: across geographies, healthcare systems and patient communities.
The size and scope of TRITON-CM clinical trial is designed to help generate meaningful data across a wide spectrum of patients living with ATTR-CM.
2. We intentionally designed the clinical trial to be more inclusive of women
ATTR-CM has historically been underdiagnosed in women, and women have been underrepresented in past ATTR-CM clinical trials. Research and clinical experience suggest that women with ATTR-CM often present differently and may be diagnosed later than men. Women also naturally tend to have smaller hearts on average than men, an important consideration in a disease where an abnormally thick heart is a diagnostic hallmark.
Based on emerging scientific literature and expert input, TRITON-CM clinical trial requires a lower interventricular septal wall thickness for women than men to be eligible for the trial. When indexed to body size, women and men have similar heart wall thickness. Past ATTR-CM clinical trials applied the same absolute threshold for men and women, which could have excluded some women from participation.
By adjusting this criterion, we aimed to ensure that women with ATTR-CM are appropriately represented in the study population.
This change reflects a broader commitment: designing trials that account for biological differences rather than overlooking them.
3. Patient insights directly informed the protocol
Before finalizing the trial protocol, we held patient interviews and focus groups to gather input from men and women living with ATTR-CM. We also engaged patient advocacy organizations and patient advisory committees to review key elements of the study.
This feedback shaped several aspects of the trial, including:
- Simplifying and revising informed consent materials to improve clarity and readability
- Reducing patient burden where possible, including visit structure and study logistics
- Considering site-level dynamics to ensure patients feel comfortable and supported throughout the process
Clinical trials work best when they are designed with patients, not just for them.
4. We are working to address real-world barriers to diagnosis and enrollment
The pathway to an ATTR-CM diagnosis can be complex. Patients often see multiple healthcare providers before reaching a specialist, and women may delay seeking care or may have symptoms attributed to other causes.
We heard from clinicians that women can face additional barriers, from differences in symptom reporting to longer diagnostic journeys. These realities informed our approach to trial awareness and engagement.
As part of our Amyloidosis Awareness Month efforts, we are collaborating with advocacy organizations and leveraging targeted educational outreach to help raise awareness of ATTR-CM and the importance of clinical research participation.
Increasing representation in clincial trials begins with increasing awareness in the community.
5. TRITON-CM reflects a broader evolution in how we design trials
At Alnylam, we have taken steps in recent years to embed patient and clinical input earlier and more systematically into clinical trial protocol development. Today, protocols are reviewed through a patient-centered lens before they are finalized to evaluate burden, accessibility and clarity.
This evolution reflects an important shift: from designing trials based solely on scientific endpoints to designing trials that balance rigor with lived experience.
TRITON-CM is one example of how that philosophy translates into action, integrating clinical evidence, expert insight and community feedback to create a more inclusive study.
Looking Ahead
Amyloidosis Awareness Month is an opportunity not only to raise awareness of ATTR-CM, but also to reflect on how clinical research can continue to evolve.
Listening to patients and clinicians is essential for transforming what we learn from TRITON-CM into practical steps to help improve the care of ATTR-CM patients in the real world.
As TRITON-CM continues enrollment globally, we remain committed to advancing research that reflects the full community of people living with transthyretin amyloidosis with cardiomyopathy (ATTR-CM).
Learn more about the TRITON-CM clinical trial here.
Additional Insights: Why did the TRITON-CM clinical trial adjust the septal wall thickness criteria for women?
In transthyretin amyloidosis with cardiomyopathy (ATTR-CM), the buildup of transthyretin amyloid protein causes abnormal thickening of the heart muscle. Thus, an increased interventricular septal wall thickness is a key diagnostic feature. The interventricular septum separates the left and right ventricles, which pump blood to the body and lungs.
However, women tend to have smaller hearts than men because women tend to be smaller. When wall thickness is measured without accounting for body size, a woman may not meet the same absolute threshold for diagnosis, even when the septum is thicker than normal. After accounting for height, women and men with ATTR-CM have similarly thick hearts.
TRITON-CM thus requires different minimum interventricular septal wall thicknesses, 11 and 12 mm, for women and men to be eligible for the trial.
By adjusting this criterion, the trial aims to:
- Recognize an emerging understanding of the differences between women and men with ATTR-CM
- Include more women who have ATTR-CM, thus supporting more representative enrollment in TRITON-CM
- Ensure that the results of TRITON-CM will help ATTR-CM patients in the real world
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