On August 9, 2021, biopharmaceutical and RNAi therapeutics company Alnylam Pharmaceuticals, Inc. (“Alnylam”) shared that enrollment is now complete for the Phase 3 HELIOS-B clinical trial. During the trial, researchers will evaluate the investigational vutrisiran, an RNAi treatment, for patients with cardiomyopathy associated with transthyretin-mediated (ATTR) amyloidosis. Altogether, over 600 patients enrolled in the HELIOS-B trial, which should provide a better understanding of effective treatment options.
Vutrisiran
According to Alnylam, vutrisiran is a subcutaneously-administered RNAi therapy which:
Inhibits the production of disease-causing transthyretin (TTR) protein by the liver, leading to a reduction in the level of TTR in the blood. Vutrisiran has been granted Orphan Drug designation in the United States and the European Union for the treatment of ATTR amyloidosis [as well as] Fast Track designation…for the treatment of polyneuropathy of hATTR amyloidosis in adults.
RNAi therapy means “RNA interference.” In basic terms, RNAi therapies silence RNA and regulate gene expression to help interfere with, and stop the effects of, disease-causing genes.
Now, researchers will evaluate the safety, efficacy, and tolerability of vutrisiran for ATTR amyloidosis within the Phase 3 HELIOS-B trial. In particular, the trial is centered around the effect on cardiomyopathy, which negatively impacts the heart muscle. Patients will receive either 25mg vutrisiran or a placebo for a period of up to 36 months. Through this, researchers will evaluate mortality rates and cardiovascular issues. The full trial results should be available at some point in 2024.
Amyloidosis
Altogether, there are six main forms of amyloidosis, a condition in which abnormal amyloid proteins accumulate throughout the body: primary, secondary, familial (ATTR & non-ATTR), dialysis-related, senile systemic (SSA/wild-type), and organ-specific. In each case, amyloid deposits accumulate in organs such as the heart or kidneys. As these amyloids build-up, it can cause organ stiffening and loss of function.
TTR gene mutations cause familial amyloidosis, also known as hereditary ATTR amyloidosis. In this form, abnormal transthyretin (TTR) proteins accumulate in the organs. In many cases, ATTR amyloidosis specifically affects the heart and nervous system. Much like amyloidosis can be broken down into categories, so can ATTR amyloidosis: familial amyloid polyneuropathy, familial amyloid cardiomyopathy, and wild-type. Symptoms vary based on the affected organs, but can include:
- Nausea and vomiting
- Unintended weight loss
- Diarrhea or constipation
- Peripheral or autonomic neuropathy
- Fatigue
- Insomnia or sleep disturbances
- Shortness of breath and/or difficulty breathing
- Heart palpitations
- Chest pain
- Swelling of the lower extremities
- Dizziness
- Appetite loss
- Proteinuria (excess protein in the urine)
