In a news release from biopharmaceutical and RNAi therapeutics company Alnylam Pharmaceuticals, Inc. (“Alnylam”), the company shared that positive data was available from the Phase 3 APOLLO-B clinical trial. Within the study, researchers evaluated patisiran (marketed under the brand name ONPATTRO) for individuals with transthyretin-mediated (ATTR) amyloidosis with cardiomyopathy.

Altogether, 360 patients with ATTR amyloidosis enrolled in the trial. During the course of the study, patients received either 0.3mg/kg patisiran or a placebo. The treatment is administered via intravenous injection. Patients received treatment every 3 weeks for a 1-year period. The study met its primary endpoint regarding the 6-Minute Walk Test, as well as its secondary endpoint of improved quality-of-life (QOL). Additionally, the data shows patisiran to be relatively safe and well-tolerated.

While safe and well-tolerated, some adverse reactions did occur. These included infusion-site reactions, joint pain, and muscle spasms. According to the ONPATTRO website, additional side effects could include headache, back and abdominal pain, shortness of breath, nausea, vitamin A deficiency, and upper respiratory tract infections.

Unfortunately, during the trial, 13 individuals passed away. Of these, 5 were in the group receiving patisiran. The remaining individuals had received a placebo.

Additional results from the APOLLO-B study will be presented in September at the 18th International Symposium on Amyloidosis.

Patisiran: An Overview

A 2018 article published in Future Medicine describes patisiran as:

a double-stranded small interfering RNA that targets a sequence within the transthyretin (TTR) messenger RNA that is conserved across wild-type and all TTR variants to decrease hepatic production of mutant and wild-type TTR. Patisiran has been consistently shown to achieve rapid onset, robust and sustained reduction of serum TTR when dosed at 0.3mg/kg body weight every three weeks.

Alnylam licensed Arbutus Biopharma LNP intellectual property to help develop their RNAi therapies. Learn more about RNAi here.

What is ATTR Amyloidosis?

Amyloidosis refers to a group of rare diseases characterized by the accumulation of abnormal proteins called amyloids. As these proteins build up throughout the body, they can cause organ stiffness and loss of function. Altogether, there are six main forms of amyloidosis: primary (AL), secondary (AA), familial (ATTR & non-ATTR), dialysis-related (DRA), senile systemic (SSA or Wild-Type), and organ-specific.

ATTR amyloidosis may be split into hereditary ATTR amyloidosis (hATTR) — which could include familial amyloid cardiomyopathy and familial amyloid polyneuropathy — or wild-type ATTR amyloidosis (wtATTR); those with the former form have a TTR mutation, while those with the latter form do not. In this case, misfolded transthyretin proteins form amyloid deposits in the heart and nervous system. Symptoms vary based on the location of the protein deposits and the affected organs. Potential symptoms can (but do not always) include:

• Insomnia
• Unintended weight loss
• Chest pain
• Appetite loss or feeling of “fullness” after eating a small amount
• Diarrhea or constipation
• Issues with bladder and/or bowel control
• Nephrotic syndrome
• Peripheral or autonomic neuropathy
• Progressively worsening fatigue
• Nausea
• Shortness of breath
• Dizziness
• Swelling of the lower extremities
• Atrial fibrillation