AstraZeneca ’s rare disease group, Alexion, has entered an exclusive global collaboration and license agreement with Neurimmune for NI006, a human monoclonal antibody currently in Phase Ib development for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM), a form of amyloidosis.

Amyloidoses are a rare group of disorders characterised by the accumulation of abnormally folded proteins in tissues, which eventually results in organ damage. In ATTR-CM, transthyretin, which primarily functions as a transport protein for thyroxine and retinol, becomes misfolded as a consequence of genetic mutations or ageing. These abnormal proteins bind together, forming amyloid fibrils that deposit in the heart. As a result, the myocardium stiffens, reducing the heart’s capacity to pump blood throughout the body and ultimately leading to heart failure. NI006 is a potential disease-modifying therapy that directly targets misfolded transthyretin, with the aim of removing amyloid fibril deposits in the heart and improving cardiac function.

AstraZeneca, which acquired rare disease specialist Alexion last July, boasts a diverse cardiovascular disease (CVD) portfolio. This includes the ATTR-CM gene silencer eplontersen, owing to a global development and commercialisation agreement with Ionis Pharmaceuticals signed last month. The new agreement with Neurimmune, which gives Alexion exclusive worldwide license to develop, manufacture and commercialise NI006, further expands the company’s reach in the field. Alexion has agreed to pay Neurimmune $30m upfront, as well as up to $730m upon reaching certain developmental, regulatory and commercial milestones, and low-to-mid-teen royalties on net sales of any approved medicine.

Until relatively recently, ATTR-CM was considered a sluggish market, with off-label generics representing the only treatment option. But innovation within this space has increased significantly in recent years, resulting in the approval of Pfizer’s Vyndaqel (tafamidis), the first approved therapy for ATTR-CM. The drug is an orally administered transthyretin stabiliser that binds to transthyretin and slows the formation of amyloid fibrils. It received approval for ATTR-CM in May 2019 in the US and in February 2020 in the EU.

According to key opinion leaders (KOLs) interviewed by GlobalData, the prior lack of approved therapies meant that up until recently, there has been little incentive to diagnose ATTR-CM. As such, it is a much under-recognised condition. KOLs anticipate, however, a sharp increase in diagnosis and treatment rates in future due to the availability of approved therapies, including the emergence of additional novel therapeutics. There are currently 11 ongoing late-stage (Phase II and Phase III) clinical trials in ATTR-CM, according to GlobalData’s clinical trial database. Notable therapies under investigation include Alnylam Pharmaceuticals’ gene silencer vutrisiran.

The recent innovative developments in ATTR-CM are expected to drive exceptional market growth in the coming years and increase interest and awareness of the disease, which will in turn encourage further investment from drug companies. Alexion’s substantial investment to secure the rights to NI006 demonstrates the company’s confidence in this market’s growth potential.