Patisiran Shows Promise in Treating Hereditary Transthyretin Amyloidosis With Polyneuropathy

Patisiran offers promising benefits for the treatment of hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN), a rare and fatal genetic disorder characterized by amyloid fibril deposits affecting multiple organs, according to a study published in Therapeutic Advances in Neurological Disorders.

Patisiran, administered intravenously at a dosage of 0.3 mg/kg every three weeks, was approved by both the FDA and EMA as the first RNA interference therapy for adults with ATTRv-PN. The treatment aims to reduce the production of both variant and wild-type transthyretin (TTR) proteins, addressing the underlying cause of the disease rather than its symptoms. The APOLLO trial, a pivotal study demonstrating its effectiveness, has paved the way for further research into this innovative therapy.

“We have performed a systematic review and meta-analysis to further clarify the efficacy and safety of patisiran for ATTRv-PN,” explained Xinyue Huang, Department of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University; Rare Disease Center, Huashan Hospital, Shanghai Medical College, Fudan University; National Center for Neurological Disorders, Shanghai, China, and coauthors. “Additionally, we examined its efficacy in populations who had liver transplantation, with cardiomyopathy and with long-term use of patisiran.”

The systematic review included 11 studies with a total of 503 patients. Results indicated a pooled responsiveness rate of 88%, suggesting that most patients experienced some level of benefit from patisiran treatment. While no statistically significant improvement was observed in the Neuropathy Impairment Score (NIS), improvements were noted in the modified Neuropathy Impairment Score plus 7 nerve tests (mNIS + 7) and the Norfolk Quality of Life-Diabetic Neuropathy Questionnaire, with p-values indicating statistical significance.

Safety assessments revealed that 84.8% of patients reported adverse events (AEs), primarily mild to moderate in severity. Common AEs included diarrhea, peripheral edema, and infusion-related reactions. Serious AEs were noted in 34% of patients; however none were attributed to patisiran itself. The study documented 37 deaths among participants, primarily due to preexisting cardiovascular conditions rather than complications from the treatment.

“Herein, this meta-analysis and systematic review provided substantial evidence that patisiran treatment is effective for patients with ATTRv-PN,” concluded the study authors.

As research continues to evolve in this field, it is anticipated that further studies will elucidate long-term outcomes and refine treatment protocols for this challenging condition.

Reference

Huang X, Sun C, Chen H, Zhao C, Lin J. Efficacy and safety of patisiran for ATTRv-PN: a systematic review and meta-analysis. Ther Adv Neurol Disord. 2024;17:17562864241273079. doi:10.1177/17562864241273079