Alnylam’s Patisiran Shows Promise for Treating FAP in Phase 2 Trial

Patisiran (ALN-TTR02) led to an improvement in average nerve dysfunction in 26 patients with familial amyloid polyneuropathy (FAP), a rare disease that causes organ or nerve malfunction.

Moreover, all 25 eligible participants in the Phase 2 open label extension (OLE) study of patisiran were enrolled in the Phase 3 APOLLO OLE trial, allowing them to continue their treatment.

FA, also known as hereditary TTR-related amyloidosis (hATTR amyloidosis), is caused by an inherited defect in the protein transthyretin (TTR). The defective TTR, called TTR amyloid,  accumulates in nerves and other organs, causing different symptoms, depending on where it is deposited in the body. In FAP, defective TTR causes nerve disease (neuropathy).

Alnylam Pharmaceuticals is a major RNAi therapeutics company. RNA interference (RNAi) is a small chemical produced in the body’s cells, mainly in the liver, that can block the production of a specific protein. In the case of patisiran, the production of TTR amyloid is blocked.

Results for the Phase 2 trial (NCT01961921) were presented at the American Academy of Neurology (AAN) 2017 Annual Meeting, held in April 2017.

New results from 26 patients showed a drop in the modified neuropathy impairment score (mNIS+7, a measure of muscle weakness and nerve malfunction) after 24 months. Skin samples from the treated patients showed significant decrease in TTR amyloid deposits.

An improvement or no change in mNIS+7 at 24 months was seen in 74 percent of patients tested.

There were no drug-related serious adverse events for up to 25 months of treatment or until treatment was discontinued because of the drug.

After receiving patisiran treatment in the Phase 2 OLE study, all 25 eligible patients were included in the APOLLO-OLE study Phase 3 trial  (NCT01960348) and 20 of them had received at least 36 months of the treatment as of April 12, 2017. Alnylam expects results from the APOLLO-OLE Phase 3 trial to be available in September of this year.

“We are encouraged to see the final 24-month results from our Phase 2 OLE, which provide continued evidence suggesting that patisiran can potentially halt or improve neuropathy progression in patients with hATTR amyloidosis,” Eric Green, Vice President, General Manager, TTR Program, said in a press release. “We are also pleased to present the first-ever clinical evidence that patisiran administration is associated with a decrease in dermal TTR amyloid burden, which we believe further supports the therapeutic hypothesis that TTR knockdown can potentially lead to reduction of amyloid deposits in the body.”