Kenny Walter is an editor with HCPLive. Prior to joining MJH Life Sciences in 2019, he worked as a digital reporter covering nanotechnology, life sciences, material science and more with R&D Magazine. He graduated with a degree in journalism from Temple University in 2008 and began his career as a local reporter for a chain of weekly newspapers based on the Jersey shore. When not working, he enjoys going to the beach and enjoying the shore in the summer and watching North Carolina Tar Heel basketball in the winter.
Alnylam plans to submit a NDA for the orphan drug used to treat hATTR with amyloidosis in adults.
New topline results have stakeholders hopeful Vutrisiran could be an effective treatment option for patients with transthyretin-mediated (ATTR) amyloidosis with polyneuropathy.
Following the topline results from the HELIOS-A phase 3 trial testing the investigational RNAi therapeutic, Alnylam Pharmaceuticals plans to submit a New Drug Application (NDA) with the FDA in 2021. They also plan on following with regulatory filings in additional countries, including Brazil, Japan, and the European Union.
The HELIOS-A Study
The investigators sough primary endpoints of the change from baseline in the modified Neuropathy Impairment Score (mNIS+7) at 9 months as compared to historical placebo data from the APOLLO phase 3 study of vutrisiran.
The HELIOS-A trial is a phase 3 global, randomized, open-label study evaluating the efficacy and safety of vutrisiran in 164 patients with hATTR amyloidosis with polyneuropathy at 57 sites in 22 countries.
Each patient was randomized in a 3:1 ratio to receive either 25 mg of the study drug (n = 122) via subcutaneous injection once ever 3 months or 0.3 mg/kg of vutrisiran (n = 42) via intravenous infusions once every 3 week for 18 months.
The research team also sought secondary endpoints of the changes in quality of life assessed by the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) and gait speed, which was assessed by the timed 10-meter walk test (10-MWT) compared to historical placebo.
Positive Initial Results
Overall, the treatment met the primary endpoints (P<0.001), as well as both secondary endpoints at 9 months, showing statistically significant results (P <0.001) for each of the Norfolk QoL-DN and 10-MWT secondary endpoints.
The investigators also found the treatment improved on the exploratory cardiac biomarker endpoint NT-proBNP (P <0.05) when compared to placebo.
Vutrisiran also presented an encouraging safety and tolerability profile with only 2 discontinuations (1.6%) because of adverse events, both due to deaths unrelated to the study drug.
There were also 2 serious adverse events consisting of dyslipidemia and urinary tract infections related to vutrisiran.
Treatment emergent adverse events occurred in 10% or more of the patients, including diarrhea, pain in extremities, fall and urinary tract infections. However, these events occurred at a similar or lower rate as compared with historical placebo.
“We are excited to report positive topline results from the HELIOS-A study, which show that vutrisiran reduces neurologic impairment and improves quality of life in patients with hATTR amyloidosis with polyneuropathy as soon as 9 months, with an encouraging safety and tolerability profile,” Akshay Vaishnaw, MD, PhD, President of R&D at Alnylam, said in a statement. In addition, we’re very pleased to see evidence for reversal of polyneuropathy manifestations of disease and also favorable effects on the exploratory cardiac endpoint, NT-proBNP. We believe that vutrisiran, as a low-dose, once-quarterly, subcutaneously administered therapy, has the potential to be a highly attractive therapeutic option for patients living with this progressive, life-threatening, multi-system disease.”
The investigators plan to examine secondary endpoints at 18 months, including the change from baseline in mNIS+7, Norfolk QoL-DN, 10-MWT, modified body mass index (mBMI), Rasch-built Overall Disability Scale (R-ODS), and serum transthyretin (TTR) levels.
They will also evaluate additional exploratory cardiac endpoint data at 18 months including NT-proBNP, echocardiographic measures and cardiac amyloid assessments with technetium scintigraphy imaging.
After the 18-month study period concludes, the patients will be eligible to receive vutrisiran for an additional 18 months as part of an open-label extension.
Stakeholders will also present the full 9-month results at a conference early in 2021, as well as the topline 18-month results.
Vutrisiran has been granted an Orphan Drug Designation by the FDA and has been granted a Fast Track designation for the treatment of the polyneuropathy of hATTR amyloidosis in adults.