FDA’s approval of Alnylam’s Onpattro marks the start of a showdown in the Orphan disease hATTR amyloidosis, with Akcea’s Tegsedi likely coming to the U.S. market in less than two months. Alnylam has used its first mover advantage to set the stage with a novel outcomes-based payment model that Akcea will have to at least match to gain a competitive foothold for reaching patients.
That the drugs notch several “firsts” is not a surprise. The Aug. 10 announcement made Alnylam Pharmaceuticals Inc.’s Onpattro patisiran the first RNAi drug to be approved -- a breakthrough 20 years in the making.
But the originality of the agreement Alnylam hammered out with Harvard Pilgrim Health Care Inc. positions the competition from the get-go to be about payment and access to patients, rather than the arguably nuanced differences in efficacy.
Onpattro also becomes the first treatment in the U.S. for polyneuropathy caused by hereditary transthyretin (TTR)-mediated amyloidosis. Approval in the EU is expected next month, after EMA’s CHMP gave a positive recommendation on July 27.
Akcea Therapeutics Inc.’s competing therapy, Tegsedi inotersen, received approval in Europe last month to treat hATTR patients with stage 1 or stage 2 polyneuropathy. The compound has an Oct. 6 PDUFA date. FDA extended the original date by three months, which according to the company was due to the volume of data the agency had to review.
The two drugs also underscore the arrival of nucleic acid therapies as clinically and commercially relevant therapeutics with the potential to address diseases that are hard to treat with traditional small molecule and antibody-based modalities.
Mechanistically, the compounds operate via different takes on gene silencing to degrade mutant TTR mRNA. Onpattro is an siRNA that targets mRNA in the cytoplasm of hepatocytes. Tegsedi is an antisense oligonucleotide that acts