In 2018, the U.S. Food and Drug Administration (FDA) approved Onpattro (patisiran) as a treatment for polyneuropathy in people with hereditary transthyretin-mediated (ATTR) amyloidosis. Onpattro is an intravenously administered, double-stranded siRNA therapy that targets the transthyretin-encoding mRNA molecule. The therapy decreases the amount of transthyretin protein made in the liver, which helps reduce the amyloid (misfolded transthyretin) deposits throughout the body.
Alnylam Pharmaceuticals, the drug’s developer, sought to expand the Onpattro label this year to include cardiomyopathy related to ATTR amyloidosis. The company had submitted data from the Phase 3 APOLLO-B clinical study; this study found that Onpattro improved function, health, and overall quality of life (QOL). Furthermore, the Cardiovascular and Renal Drugs Advisory Committee voted in September that the benefits of Onpattro outweighed the potential risks within this patient population.
However, as reported by Tristan Manalac in BioSpace, the FDA denied Alnylam’s bid for label expansion and went against the Committee’s recommendations. In the FDA’s Complete Response Letter, the FDA explained that there was not enough data to specifically support Onpattro’s benefits for people with ATTR amyloidosis-related cardiomyopathy.
While Alnylam no longer plans to pursue a label expansion for Onpattro, the company is still exploring potential therapeutic options, such as vutrisiran.
About Hereditary ATTR Amyloidosis
Hereditary ATTR amyloidosis is a familial subtype of amyloidosis caused by TTR gene mutations. There are three subtypes of hereditary ATTR amyloidosis: familial amyloid cardiomyopathy, familial amyloid polyneuropathy, and wild-type ATTR amyloidosis. Right now, treatment options include TEGSEDI, ONPATTRO, and a liver transplant. For those with the cardiomyopathy form, additional treatments include VYNDAMAX and VYNDAQUEL.
Symptoms vary based on the specific underlying genetic mutation, affected organ(s), and extent of damage. Potential symptoms may include:
- Atrial fibrillation
- Chest pain
- Swollen legs and ankles
- Worsening fatigue
- Peripheral or autonomic neuropathy
- Nausea
- Unintentional weight loss
- Insomnia
- Dizziness or lightheadedness when standing
- Sexual dysfunction
- Diarrhea or constipation
- Shortness of breath
- Changes in bladder control
- Appetite loss
- Excess protein in the urine
