Vutrisiran, The World's Fourth RNAi Therapy, Is About to Submit A Marketing Application

After more than 20 years of ups and downs, the era of RNAi therapy finally here.

On January 7, 2021, Alnylam, a leading RNAi therapy research and development company, announced positive results from its Phase III trials on its RNAi therapy Vutrisiran Alnylam plans to submit the complete data package to the FDA in early 2021 and a new drug listing application (NDA). Vutrisiran, like the first RNAi drug Patisiran (intravenous preparation) (also developed by Alnylam), is used to treat neurological damage caused by hereditary thyroxine amyloidosis (hATTR). After its approval, Vutrisiran will complement Patisiran.

Figure 1: Silencing TTR gene expression can potentially address the underlying cause of disease.

About ATTR

Thyroxine amyloidosis (ATTR) is a rare, progressive, and fatal disease that causes systemic failure due to the deposition of insoluble substances.

• Hereditary ATTR (hATTR) is a specific DNA mutation in the TTR gene carried by a person at birth. This mutation causes the liver to produce and form (and accumulate) misfolded transthyretin in the body.
• hATTR manifests as multiple neuropathy (hATTR-PN), which can lead to nerve damage, or cardiomyopathy (hATTR-CM), which involves myocardial disease and can lead to heart failure. Non-mutated or wild-type TTR protein can also accumulate in the body, resulting in wild-type ATTR (wtATTR), which mainly affects the heart, especially in men ˃60 years old.
• It is estimated that there are 50,000 hATTR patients and approximately 200,000 to 500,000 wATTR patients worldwide.

Figure 2: Mechanism of amyloid formation (Morie A. Gertz, 2019).

About Vutrisiran

Vutrisiran is a subcutaneously injected RNAi therapy that uses enhanced stability chemistry (ESC)-GalNAc delivery technology to reduce target gene expression and block the production of wrong proteins by mediating target mRNA degradation and silencing mRNA translation, leaading to the inhibition of hATTR disease progression. Compared with Patisiran, the administration of Vutrisiran is more convenient. Patients undergoing experimental treatment receive a subcutaneous injection every three months.

Once Vutrisiran is approved, RNAi technology will become a reproducible drug platform to generate, innovative drugs for the treatment of rare genetic diseases, cardiometabolic diseases, liver infections, and central nervous system (CNS)/eye diseases.

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