FDA Approves First-Ever RNAi Drug

In science, and especially in the biotech sphere, it’s easy to be allured by the sudden breakthrough—the quick and glamorous new drug. But, in that sense, the field of RNA interference has been a bit of an anomaly. Nearly a generation passed between the promise of a drug therapy that muted specific disease-causing genes and an actual example of one that works in humans.

The latter came last week when the U.S. Food and Drug Administration approved the first-ever drug based on RNA interference, or RNAi. The drug, patisiran, was developed by Cambridge-based biotech Alnylam and targets a rare genetic disease, called hereditary transthyretin amyloidosis, which impairs heart and nerve function.

Patisiran was developed by Cambridge-based biotech Alnylam.

The landmark approval is a culmination of nearly two decades’ worth of research and has been described as one that will surely rewrite pharmacology textbooks. Research into RNAi grew in the early 2000s after two U.S. geneticists discovered the mechanism in 1998 and subsequently won a Nobel prize in 2006. In the years following, however, despite a rise of RNAi-based biotechs like Alnylam, no tangible treatments surfaced. Eventually, the field saw a domino effect of lost interest from investors and, eventually, the drug research community.

The main problem that Alnylam and others had to solve was one of delivery. Getting RNA to a specific organ meant protecting it from degrading in the bloodstream and being filtered out by the kidneys or liver so it can go on to exit the blood vessels and spread through tissue. Here’s Heidi Ledford, reporting for Nature:

But gradually, some RNAi companies began to iron out the kinks in their delivery systems, and Tenthoff started to encourage investors to buy stock again. Alnylam experimented with a number of delivery routes and target organs, encasing some of its RNA molecules in fatty nanoparticles orchemically modifying the RNAs to help them survive the perilous journey through the bloodstream.

RNAs protected in this way and injected into the bloodstream tended to accumulate in the kidneys and liver. This led the company to look at transthyretin, which is produced mainly in the liver. In a clinical trial in 225 people with hereditary transthyretin amyloidosis who showed signs of nerve damage, average walking speed significantly improved in those who received the treatment. Walking speed declined in the placebo group.

Questions remain about whether the technique will work in other parts of the body. But, according to Alnylam company officials, the liver is just the starting point; the company is working to develop ways to target the brain and spinal cord. Other companies are also looking at RNAi therapies that target the kidneys, eyes, and lungs.

Watch a trailer for NOVA’s RNA Lab, then play the game here.