General Information

Amvuttra (vutrisiran) is a transthyretin-directed small interfering RNA.

Amvuttra is specifically indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults.

Amvuttra is supplied as an injection for subcutaneous administration. The recommended dosage is 25 mg administered by subcutaneous injection once every 3 months. If a dose is missed, administer Amvuttra as soon as possible. Resume dosing every 3 months from the most recently administered dose.

Mechanism of Action

Amvuttra (vutrisiran) is a double-stranded siRNA-GalNAc conjugate that causes degradation of mutant and wild-type TTR mRNA through RNA interference, which results in a reduction of serum TTR protein and TTR protein deposits in tissues.

Side Effects

Adverse effects associated with the use of Amvuttra may include, but are not limited to, the following:

• arthralgia
• dyspnea
• vitamin A decreased

Clinical Trial Results

The FDA approval of Amvuttra was based on 9-month results from the HELIOS-A Phase 3 study, a global, randomized, open-label, multicenter study that evaluated the efficacy and safety of Amvuttra in 164 patients with hATTR amyloidosis. Patients were randomized 3:1 to receive either 25 mg of vutrisiran (N=122) via subcutaneous injection once every three months or 0.3 mg/kg of patisiran (N=42) via intravenous infusion once every three weeks (reference group) for 18 months. Efficacy was assessed by comparing the Amvuttra group in HELIOS-A with the placebo group (n=77) from the landmark APOLLO Phase 3 study of patisiran, a randomized controlled study in a comparable patient population.

Amvuttra met the primary endpoint of the study, the change from baseline in the modified Neuropathy Impairment Score + 7 (mNIS+7) at 9 months. Treatment with Amvuttra (N=114) resulted in a 2.2 point mean decrease (improvement) in mNIS+7 from baseline as compared to a 14.8 point mean increase (worsening) reported for the external placebo group, resulting in a 17.0 point mean difference relative to placebo. By 9 months, 50 percent of patients treated with Amvuttra experienced improvement in neuropathy impairment relative to baseline.

Amvuttra also met all secondary endpoints in the study at 9 months, with significant improvement in the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy score and timed 10-meter walk test (10-MWT), and improvements were observed in exploratory endpoints, including change from baseline in modified body mass index (mBMI), all relative to external placebo. Efficacy results at 18 months were consistent with 9-month data.