Cardiac complications continue to be at the forefront of medical challenges, with Transthyretin amyloidosis (ATTR amyloidosis) representing a significant concern. ATTR amyloidosis manifests through the accumulation of amyloid deposits in the heart, progressively leading to cardiomyopathy and deteriorating heart function. Addressing this, the therapeutic horizon has expanded to embrace RNA interference agents like Patisiran, which suppress the production of hepatic transthyretin, potentially offering a novel avenue for treatment. This article delves into the findings of the APOLLO-B Trial, a comprehensive phase 3 study designed to gauge the efficacy, safety, and potential clinical implications of Patisiran in treating ATTR amyloidosis.
Cardiac Amyloidosis Credit: Nephron
Study Design and Methodology
Led by a team of researchers, including Drs. Mathew S. Maurer, Parag Kale, Marianna Fontana, and others, the APOLLO-B Trial sought to evaluate Patisiran’s (Onpattro) impact in a controlled, randomized environment.
Participants: The study included patients diagnosed with either hereditary (variant) or wild-type ATTR cardiac amyloidosis.
Intervention: Patients were randomly allocated in a 1:1 ratio to receive either Patisiran (0.3 mg/kg body weight) or a placebo, with administrations scheduled once every three weeks across a 12-month period.
Primary Endpoint: The central evaluative metric was the alteration in the 6-minute walk test distance after 12 months relative to the baseline.
Secondary Endpoints: Three secondary measures were also in focus:
- The shift in the Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS) score at the end of the 12 months.
- A composite index capturing all-cause mortality, cardiovascular incidents, and variations in the 6-minute walk test distance within the year.
- Another composite measure assessing all-cause mortality, hospitalizations irrespective of cause, and emergency heart failure visits during the 12-month timeframe.
Results and Observations
Of the total 360 enrollees, 181 were designated to the Patisiran bracket and 179 to the placebo group. A year into the intervention, the study unveiled:
- A notable reduction in the decline of the 6-minute walk distance for the Patisiran group compared to the placebo (median difference estimated at 14.69 m; 95% CI of 0.69 to 28.69; P=0.02).
- An upward trend in the KCCQ-OS scores for the Patisiran group, contrasting with a downward shift in the placebo (mean difference of 3.7 points; 95% CI from 0.2 to 7.2; P=0.04).
- The second secondary metric did not present any statistically significant advantages.
- Adverse reactions linked to the infusion, muscle spasms and joint pain were more prevalent in the Patisiran recipients than in the placebo recipients.
Discussion
The APOLLO-B Trial’s results underline the importance of continuous exploration into innovative therapeutics for conditions as intricate as ATTR amyloidosis. For clinicians, these findings signify not just a potential treatment avenue but also a shift in managing the disease. While the primary and one of the secondary endpoints indicated statistically significant improvements with Patisiran, it’s essential for practitioners to weigh these benefits against the observed adverse reactions, ensuring an individualized, patient-centered approach.
Dr. Tamipiwa Chebani, our senior editor at Gilmore Health, commented on the study, stating, “The APOLLO-B Trial’s outcomes are indeed promising. As we navigate the complex waters of ATTR amyloidosis treatments, studies like these offer hope. The results underscore the importance of combining rigorous scientific inquiry with clinical application.”
Final thoughts
A 12-month trial with Patisiran showcased its potential to safeguard the functional capacities of individuals grappling with ATTR cardiac amyloidosis. While the findings highlight its promise, it’s vital to juxtapose the benefits against potential side effects. Subsequent research can offer deeper insights into Patisiran’s enduring impact and strategies to counter potential adverse reactions.
References
Maurer, M. S., Kale, P., Fontana, M., Berk, J. L., Grogan, M., Gustafsson, F., Hung, R. R., Gottlieb, R. L., Damy, T., González-Duarte, A., Sarswat, N., Sekijima, Y., et al. (2023). Patisiran Treatment in Patients with Transthyretin Cardiac Amyloidosis. New England Journal of Medicine, 389(16), 1553-1565. https://doi.org/10.1056/NEJMoa2300757
