**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Martha Grogan
Mayo Clinic, Rochester, MN, USA

**Main Body of the Abstract**
ATTR amyloidosis is a progressive, debilitating disease resulting from accumulation of toxic TTR fibrils leading to multi-system tissue injury.  We evaluated the efficacy and safety of RNAi therapeutics (patisiran and vutrisiran) across pivotal and real-world studies.
RNAi therapeutics have been studied for 10 years across trials with patients representing a broad spectrum of disease etiology, manifestations, and burden (816 patients and 2299 patient-years of treatment; Figure).
Patients treated with RNAi therapeutics demonstrated rapid serum TTR knockdown (>85% reduction) with indication of effect on cardiac and neurologic biomarkers (NT-proBNP, troponin I/T, NfL) at 3–6 months. Beneficial effect on cardiac structure and function (nominal significance in LV mass, stroke volume, GLS at 12m in APOLLO-B; LV wall-thickness, GLS, cardiac output, LVEDV at 18m in APOLLO; cardiac output, LVEDV at 18m in HELIOS-A) and 99mTC uptake was observed.  Statistically significant benefits vs placebo in clinical status (mNIS+7 –33.99pts, mBMI 115.7, 10-MWT 0.31m/s at 18m in APOLLO; mNIS+7 –28.55pts, mBMI 140.7, 10-MWT 0.239m/s at 18m in HELIOS-A; 6-MWT 14.69pts in APOLLO-B at 12m) and QoL (Norfolk-QOL –21.1pts, RODS 9.0pts, EQ-VAS 9.5pts at 18m in APOLLO; Norfolk-QOL –21.1pts, RODS 8.4pts, EQ-VAS 13.7pts at 18m in HELIOS-A; KCCQ 3.7pts at 12m in APOLLO-B) were observed at 6–9 months.
Across studies, RNAi therapeutics were well tolerated; most AEs were mild or moderate in severity and consistent with those expected in ATTR amyloidosis.
Patients representing a diverse ATTR population treated with RNAi therapeutics in long-term clinical and real-world studies demonstrate favorable efficacy and safety.



**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Martha Grogan
Mayo Clinic, Rochester, MN, USA

**Main Body of the Abstract**
ATTR amyloidosis is a progressive, debilitating disease resulting from accumulation of toxic TTR fibrils leading to multi-system tissue injury.  We evaluated the efficacy and safety of RNAi therapeutics (patisiran and vutrisiran) across pivotal and real-world studies.
RNAi therapeutics have been studied for 10 years across trials with patients representing a broad spectrum of disease etiology, manifestations, and burden (816 patients and 2299 patient-years of treatment; Figure).
Patients treated with RNAi therapeutics demonstrated rapid serum TTR knockdown (>85% reduction) with indication of effect on cardiac and neurologic biomarkers (NT-proBNP, troponin I/T, NfL) at 3–6 months. Beneficial effect on cardiac structure and function (nominal significance in LV mass, stroke volume, GLS at 12m in APOLLO-B; LV wall-thickness, GLS, cardiac output, LVEDV at 18m in APOLLO; cardiac output, LVEDV at 18m in HELIOS-A) and ^99m^TC uptake was observed.  Statistically significant benefits vs placebo in clinical status (mNIS+7 –33.99pts, mBMI 115.7, 10-MWT 0.31m/s at 18m in APOLLO; mNIS+7 –28.55pts, mBMI 140.7, 10-MWT 0.239m/s at 18m in HELIOS-A; 6-MWT 14.69pts in APOLLO-B at 12m) and QoL (Norfolk-QOL –21.1pts, RODS 9.0pts, EQ-VAS 9.5pts at 18m in APOLLO; Norfolk-QOL –21.1pts, RODS 8.4pts, EQ-VAS 13.7pts at 18m in HELIOS-A; KCCQ 3.7pts at 12m in APOLLO-B) were observed at 6–9 months.
Across studies, RNAi therapeutics were well tolerated; most AEs were mild or moderate in severity and consistent with those expected in ATTR amyloidosis.
Patients representing a diverse ATTR population treated with RNAi therapeutics in long-term clinical and real-world studies demonstrate favorable efficacy and safety.



A unified analysis of the impact of rapid TTR knockdown by RNAi therapeutics across transthyretin-mediated (ATTR) amyloidosis studies PC109 (#182)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.