Rare Disease Report

Phase 3 Amyloidosis Trial Completes Enrollment

JANUARY 31, 2016
James Radke, PhD
APOLLO Phase 3 clinical trial— examining the safety and efficacy of patisiran to treat TTR-mediated amyloidosis (ATTR amyloidosis) in patients with familial amyloidotic polyneuropathy (FAP)—has completed its enrollment of over 200 patients.
 
Results are expected in 2017 and if the data is positive, Alnylam Pharmaceuticals plans to submit a New Drug Application (NDA) in late 2017.  And until then, the company plans to keep silent on the results. No interim analyses are planned.
 
ATTR amyloidosis is an inherited, progressive, and life-threatening orphan disease affecting approximately 50,000 patients worldwide, including approximately 10,000 persons with FAP.
 
In a press release, Eric Green, general manager of the TTR Program  at Alnylam stated, “ATTR amyloidosis, including FAP, is a generally fatal, orphan disease with limited treatment options. We believe data reported to date in our clinical studies provide encouraging preliminary evidence for patisiran’s clinical activity and tolerability, while definitive evidence to support registration awaits results from our randomized, placebo-controlled study. Accordingly, we’re excited to have rapidly completed enrollment in our APOLLO Phase 3 study."
 
Green added, “Regarding our decision to forego an interim analysis for efficacy, our timely and highly competitive completion of APOLLO enrollment supports our continued plan to file an NDA and MAA with a full and comprehensive analysis of primary and secondary endpoint data in 2017, if the study is positive.”

APOLLO Study

The APOLLO Phase 3 trial is a randomized, double-blind, placebo-controlled, global study designed to evaluate the efficacy and safety of patisiran (0.3 mg/kg once every 3 weeks for 8 months) in patients with FAP (N=225).
 
The primary endpoint of the study is the difference in the change in a modified neuropathy impairment score, “mNIS+7,” from baseline to 18 months between patisiran and placebo. mNIS+7 measures disease progression including muscle weakness, impaired reflexes, and changes in other sensory measures.
 
Secondary study endpoints include: the Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) score; modified body mass index (mBMI); timed 10-meter walk; an autonomic symptom score called “COMPASS-31,” amongst other endpoints. In addition, nerve regeneration by measurement of sweat gland nerve fiber density will be assessed in patients who elected to provide skin punch biopsy samples.

About TTR Amyloidosis 

Transthyretin (TTR) is a protein that helps control the transportation of vitamin A in the body. Mutations of the TTR gene can lead to abnormal folding of the TTR protein that in turn results in deposits of the amyloid fibril proteins in various organs and tissues. Where they deposit will determine the symptoms. For example, patients with familial amyloidotic polyneuropathy (FAC) have cardiac deposits and may show symptoms of congestive heart failure and/or severe postural hypotension whereas patients with FAP have neuropathic deposits and common symptoms will be hyperalgesia, lower or upper limb neuropathy, etc.
 
At present there is no pharmacologic therapy available for patients with TTR amyloidosis and treatment will be determined based on the organ involved.
 

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