Patisiran Offers New Hope for Patients Battling ATTR Cardiac Amyloidosis

In a pivotal development, a groundbreaking phase 3 clinical trial has revealed positive outcomes for patients grappling with transthyretin amyloidosis, commonly known as ATTR amyloidosis. The study found that innovative RNA interference therapeutic agent, patisiran, demonstrated promising results by preserving functional capacity and providing fresh hope for patients with hereditary or wild-type ATTR cardiac amyloidosis.

The study results were published in the journal The New England Journal of Medicine. 

Transthyretin amyloidosis, also called ATTR amyloidosis, is a progressive, debilitating, and fatal disease caused by misfolded transthyretin protein that accumulates as amyloid fibrils in multiple organs, including the heart, nerves, gastrointestinal tract, and musculoskeletal tissues. This challenging medical condition often leads to progressive cardiomyopathy, a condition that hampers the heart's ability to pump blood efficiently. Previous research from the Apollo trial found that Patisiran, an RNA interference therapeutic agent, inhibited the production of hepatic transthyretin and provided therapeutic benefits in cardiac amyloid. Hence, researchers conducted a phase 3, double-blind, randomized trial to assess the primary efficacy and safety of patisiran in patients with variant or wild-type ATTR cardiac amyloidosis.

The clinical trial, conducted in phase 3, double-blind, randomized fashion, engaged 360 participants afflicted by hereditary (or variant) and wild-type ATTR cardiac amyloidosis. These patients were evenly split into two groups, with a 1:1 ratio. The trial involved administering patisiran at a dose of 0.3 mg per kilogram of body weight or a placebo. The treatment was delivered at three-week intervals and spanned a period of 12 months.

The study encompassed both primary and secondary endpoints to gauge the effectiveness of patisiran. The primary endpoint was to assess the change in the distance covered during the 6-minute walk test at the 12-month mark, a crucial measure of functional capacity. The secondary endpoints included:

1. Evaluating the change in the Kansas City Cardiomyopathy Questionnaire–Overall Summary (KCCQ-OS) score, which provides insights into the patient's overall health status.
   
2. An assessment of a composite endpoint that considered death from any cause, cardiovascular events, and the change in the 6-minute walk test distance over 12 months.
3. A comprehensive examination of a composite endpoint comprising death from any cause, hospitalizations for any reason, and urgent heart failure visits over the same 12-month duration.

Results:

• There were 181 in the patisiran group and 179 in the placebo group.
• Patients who received patisiran exhibited a notably lower decline in the distance covered during the 6-minute walk test in comparison to the placebo group.
• Moreover, the partisan-treated group displayed an increase in the KCCQ-OS score, reflecting improved health status.
• Conversely, the placebo group experienced a decline in their scores, indicating a worsening health status.
• For the secondary endpoints, patisiran did not yield substantial advantages. 
• During the course of the trial, some patients receiving patisiran reported infusion-related reactions, arthralgia (joint pain), and muscle spasms more frequently than those in the placebo group. 

In conclusion, this groundbreaking trial signifies a significant breakthrough in the treatment of ATTR cardiac amyloidosis. The administration of patisiran over the 12-month period has demonstrated the potential to preserve functional capacity in patients afflicted by this challenging condition, which can significantly enhance their overall quality of life. This study marks a significant stride toward the development of effective treatments for ATTR cardiac amyloidosis, ultimately holding the promise of improving the lives of countless patients grappling with this complex medical condition. The results offer hope for better therapeutic options and outcomes in the ongoing battle against amyloidosis.

Further reading: Patisiran Treatment in Patients with Transthyretin Cardiac Amyloidosis. N Engl J Med 2023; 389:1553-1565. DOI: 10.1056/NEJMoa2300757