The purpose of this study is to evaluate the safety and efficacy of patisiran (ALN-TTR02)
in patients with transthyretin (TTR) mediated amyloidosis. An open-label, single-arm,
long-term follow-up extension study NCT02510261 (ALN-TTR02-006) was initiated to provide
participants who completed this study with continued patisiran-LNP (lipid nanoparticle)
treatment.

APOLLO: The Study of an Investigational Drug, Patisiran (ALN-TTR02), for the Treatment of Transthyretin (TTR)-Mediated Amyloidosis

Transthyretin Amyloidosis (ATTR)

Patisiran

Clinical Trial Site

APOLLO: A Phase 3 Multicenter, Multinational, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of Patisiran (ALN-TTR02) in Transthyretin (TTR)-Mediated Polyneuropathy (Familial Amyloidotic Polyneuropathy-FAP)

The difference between the patisiran (ALN-TTR02) and placebo groups in the change from
baseline in mNIS+7 at 18 months. The mNIS+7 is a composite score that quantitates motor,
sensory, and autonomic neurologic impairment due to injury of large and small nerves. The
minimum and maximum values are 0 and 304, respectively. A higher score indicates a worse
outcome.

The difference between the patisiran (ALN-TTR02) and placebo groups in the change from
baseline in Norfolk QoL-DN at 18 months. The Norfolk QoL-DN questionnaire is a
standardized 35-item patient-reported outcomes measure that is sensitive to the different
features of diabetic neuropathy - small fiber, large fiber, and autonomic nerve function.
The minimum and maximum values are -4 and 136, respectively. A higher score indicates a
worse outcome.

The difference between the patisiran (ALN-TTR02) and placebo groups in the change from
baseline in NIS-W at 18 months. NIS-W is a measure of motor strength, comprised of
cranial nerve and both upper and lower limb motor assessments. The minimum and maximum
values are 0 and 192, respectively. A higher score indicates a worse outcome.

The difference between the patisiran (ALN-TTR02) and placebo groups in the change from
baseline in R-ODS score at 18 months. The R-ODS is comprised of a 24-item linearly
weighted scale that specifically captures activity and social participation limitations
in patients. The minimum and maximum values are 0 and 48, respectively. A higher score
indicates a better outcome.

The difference between the patisiran (ALN-TTR02) and placebo groups in the change from
baseline in 10-MWT at 18 months. Ability to ambulate (gait speed) was assessed through
the 10-meter walk test (10-MWT). The walk had to be completed without assistance from
another person; ambulatory aids such as canes and walkers were permitted.

The difference between the patisiran (ALN-TTR02) and placebo groups in the change from
baseline in mBMI at 18 months. The nutritional status of patients was evaluated using the
mBMI; calculated as the product of BMI (weight in kilograms divided by the square of
height in meters) and serum albumin (g/L).

The difference between the patisiran (ALN-TTR02) and placebo groups in the change from
baseline in COMPASS 31 at 18 months. The COMPASS 31 is a measure of autonomic neuropathy
symptoms. The questions evaluated 6 autonomic domains (orthostatic intolerance,
vasomotor, secretomotor, gastrointestinal, bladder, and pupillomotor). The minimum and
maximum values are 0 and 100, respectively. A higher score indicates a worse outcome.