Two deals riding on the coattails of Alnylam Pharmaceuticals' first US approval for an RNA interference drug have seen billions flowing into the space. In October, Janssen Pharmaceuticals paid Arrowhead Pharmaceuticals $175 million in cash for rights to an RNAi product designed to silence two regions in the hepatitis B virus (HBV) genome, in a deal worth up to $1.6 billion. The deal followed the release of striking interim results from a phase 1/2 trial with the biotech's ARO-HBV (AROHBV1001) candidate. In the same month, Dicerna Pharmaceuticals received $100 million up front and $100 million in equity investment from Eli Lilly to use Dicerna's GalXC RNAi platform for generating oligonucleotide therapeutic agents in cardiometabolic disease, neurodegeneration and pain. Arrowhead's study in eight HBV-infected patients achieved a 96–99% drop in circulating HBV surface antigen in the groups treated with the two lowest doses of the drug. Chronic HBV infection can lead to cirrhosis and liver cancer. Standard of care requires long-term treatment with PEGylated interferons or oral nucleoside or nucleotide analogs, which stop viral replication.

The recent results are remarkable considering that in November 2016 Arrowhead's intravenous delivery vehicle for a second-generation RNAi drug was found to be toxic to nonhuman primates. The FDA put a stop on Arrowhead's phase 2 trial of the drug, and the company's stock plummeted. Arrowhead decided to abandon the programs and develop a new delivery technology, Targeted RNAi Molecule (TRiM), which they used to develop the candidates tested in the most recent trial. ARO-HBV contains two siRNAs. Arrowhead was due to present more AROHBV1001 trial data at the Liver Meeting in November, as Nature Biotechnology went to press.

Dicerna also entered a deal with Alexion Pharmaceuticals in late October focused on the discovery and development of RNAi therapies to block the uncontrolled complement activation that drives many diseases. Dicerna received $22 million up front and an equity investment of $15 million, with potential for additional milestones and royalties.