Sanofi SA / Alnylam Pharmaceuticals Inc.

Hereditary Transthyretin (hATTR) Amyloidosis

Disease Overview

Hereditary ATTR amyloidosis is a rare, progressive, multisystem genetic disease caused by mutations in the TTR gene that produce misfolded transthyretin protein, which deposits as amyloid fibrils in peripheral nerves, the heart, and GI tract. Untreated, the polyneuropathy form is debilitating and fatal within roughly 5-15 years of symptom onset, with very limited disease-modifying options before 2018.

Competitive Landscape

At deal signing in January 2014, Pfizer's tafamidis (Vyndaqel) was the only TTR-targeting agent on the market, and only outside the US, leaving hATTR patients globally with essentially no disease-modifying options beyond off-label diflunisal and liver transplant. Alnylam's RNAi platform was the most advanced gene-silencing approach, with patisiran in Phase 3 (APOLLO) and revusiran in development for ATTR cardiomyopathy. The Sanofi-Genzyme deal anchored RNAi as a credible rare-disease modality after Merck, Roche, and Novartis had abandoned the technology between 2006-2010 over delivery hurdles. Patisiran (Onpattro) ultimately became the first FDA-approved RNAi therapeutic in August 2018, validating the platform; Ionis/Akcea's antisense competitor Tegsedi (inotersen) followed weeks later. The 2018 restructuring returned full ATTR rights to Alnylam and gave Sanofi global rights to fitusiran for hemophilia, with Sanofi taking up to 25% royalties on patisiran in territories it relinquished. Today the hATTR market is contested across patisiran, vutrisiran (Amvuttra), inotersen, and the tafamidis franchise (Vyndaqel/Vyndamax), with TTR silencers competing against TTR stabilizers.