Onpattro’s approval was a critical milestone for the field of RNA therapeutics.
In August, the US Food and Drug Administration gave its blessing to Alnylam Pharmaceuticals’ Onpattro, making it the first RNA interference therapeutic to reach the market. The green light was a high point in a year that has brought a flood of money and attention to companies working on ways to harness RNA.
The approval of Onpattro, which treats a rare genetic disorder called hereditary transthyretin-mediated amyloidosis, is the culmination of 16 years of elbow grease at Alnylam, which began pursuing RNAi therapeutics just four years after researchers discovered that double-stranded RNA can silence genes.
In the early days, “there was a huge amount of enthusiasm without a lot of data,” recalls Alnylam CEO John Maraganore. “We had to figure out all the technical hurdles, and that led to a few years in the middle where many people gave up hope. We never gave up. We stuck with it, and now we’re seeing a period of time where there really is an appropriately data-driven sense of optimism for where this can go.”
A few hurdles remain. Alnylam, which expects to ask the FDA to approve a second RNAi therapeutic next year, needs to show its products can succeed commercially. And everyone would like to see more clinical evidence that the approach can work outside the liver, where the firm’s RNAi therapies tend to congregate.
But for researchers working in RNA therapeutics of any flavor—small interfering RNA, antisense oligonucleotides, messenger RNA vaccines, or newer approaches—excitement over this first milestone is palpable.
“This year has been wonderful for the field,” says Frank Slack, director of the Institute for RNA Medicine at Beth Israel Deaconess Medical Center. Researchers trying to develop RNA-based therapeutics have long been dogged by three main issues: delivery, stability, and toxicity. “I’ve always had the sense that once one can solve those . . . the flood gates would open,” Slack says. “I’m very optimistic that the field is about to enter an exponential growth phase.”
I’m very optimistic that the field is about to enter an exponential growth phase.
Frank Slack,, director, Institute for RNA Medicine, Beth Israel Deaconess Medical Center
Indeed, researchers continue to build on the promise of other ways to modulate RNA.
One high-profile example came in October, when a researcher at Boston Children’s Hospital reported quickly developing a personalized antisense oligonucleotide for a girl with an ultrarare neurological disorder called Batten disease. The FDA granted special permission for the child to receive the homegrown therapy, which so far appears to be slowing the progression of her disease.
That work came on the heels of success for Spinraza, a spinal muscular atrophy treatment from Biogen and Ionis Pharmaceuticals. Approved in 2016, Spinraza has bolstered confidence that antisense oligonucleotides can be powerful tools for treating neurological disorders.
In April, Biogen committed another $1 billion to Ionis through a 10-year neuroscience-focused pact. And investors sunk significant cash into several new antisense companies, including Stoke Therapeutics, which has raised $130 million since its launch in January.
While RNA-based therapeutics are flourishing, this year also brought a crop of companies trying to use small molecules to wrangle RNA. New firms like Expansion Therapeutics and Ribometrix are designing molecules to inhibit the RNA that encodes for disease-causing proteins. Meanwhile, several firms emerged to target the proteins and enzymes that modify RNA, a field known as epitranscriptomics.
The companies taking a small-molecule approach are years away from the market, but they’ve attracted significant funding from venture capital firms.
Slack is a cofounder of one such start-up, Twentyeight-Seven Therapeutics, which in September raised $65 million in its first round of financing. He expects the momentum to continue. “It’s definitely a growth area, and we’ll see many more examples of these starting up around the country.”