Alnylam Submits New Drug Application in Japan for Patisiran in Treatment of Hereditary ATTR Amyloidosis

Iqra Mumal, MSc avatar

by Iqra Mumal, MSc |

Share this article:

Share article via email
FAP therapies, Prix Galien Awards

Alnylam Pharmaceuticals announced the submission of a New Drug Application (NDA) to Japan’s Pharmaceuticals and Medical Devices Agency (PMDA) for  the approval of patisiran as a treatment for hereditary transthyretin-mediated (hATTR) amyloidosis.

hATTR amyloidosis, also known as familial amyloid polyneuropathy (FAP), is caused by mutations in the TTR gene. It is characterized by the accumulation of misfolded transthyretin (TTR) protein in body organs and tissue.

Patisiran, approved as Onpattro in the United States, is an RNAi therapy designed to target the TTR protein. In particular, it targets a pre-protein molecule called mRNA, which stops the production of TTR.

By blocking the production of TTR in the liver, patisiran reduces the accumulation of TTR in the body’s tissue and helps slow progression of the disease.

Patisiran has already received orphan drug designation from the Ministry of Health, Labor and Welfare (MHLW) in Japan, which grants the medicine priority review and 10 years of market exclusivity.

Alnylam anticipates a decision from the MHLW and PMDA in 2019. Patisiran is Alnylam’s first therapeutic to be submitted for regulatory review in Japan.

“The NDA submission highlights Alnylam’s continued commitment to bring RNAi therapeutics to patients in need with the potential to make a meaningful impact on serious rare diseases that have devastating effects on the lives of patients and their families,” Masako Nakamura, Alnylam’s senior vice president and head of Asia, said in a press release.

“Hereditary ATTR amyloidosis is [frequently found] in Japan, with V30M being the most common mutation. We look forward to working with the PMDA during the review process so that we can make patisiran available to patients as expeditiously as possible,” Nakamura said.

The NDA submission was conducted based on previously accumulated data from the APOLLO Phase 3 clinical trial (NCT01960348), which assessed the efficacy and safety of patisiran in treatment of FAP patients.

The results were published in a study in the The New England Journal of Medicine.

Among the 225 patients in the study, 16 were from Japan. The participants received either patisiran or a placebo once every three weeks for a year and a half.

Results indicated that patisiran improved neuropathy (nerve disease), quality of life, activities of daily living, ability to move, overall nutrition and other functions compared to the placebo. Adverse events were comparable between patients receiving either patisiran or the placebo.

The most frequent adverse events were peripheral edema (swelling) and reactions to infusions of the drug.

In August 2018, the U.S. Food and Drug Administration (FDA) approved patisaran for treatment of polyneuropathy in hATTR. Also in August 2018, patisiran received marketing authorization from the European Commission for treatment of hATTR amyloidosis in adults with stage one or stage two polyneuropathy.