Gung ho: Alnylam lands historic FDA OK on patisiran, revving up the first global rollout for an RNAi breakthrough

“A lot of people think it’s winter out there for RNAi. But I think it’s springtime.” — Alnylam CEO John Maraganore, NYT, February 7, 2011.

Marketing season has officially arrived for RNAi, just two decades in the making.

On Friday, the FDA approved Alnylam’s patisiran, offering a historic green light for a drug that is breaking the waves in therapeutic innovation.

Over the past 16 years since Alnylam $ALNY was founded, John Maraganore has seen everything when it comes to RNAi. He benefited from the early promise and rush of Big Pharmas looking to get a foot in the door, lured in by tech that promised to switch genes on and off. 

Then he watched most of the majors leave during the season of discontent he referenced above — in a 2011 interview with Andrew Pollack at The New York Times — usually shrugging off some heavy losses on their way out the exit. Maraganore came back with the 5X15 pledge at the beginning of 2011, promising to hustle 5 RNAi drugs into late-stage development by 2015. And now he’s survived it all to turn the switch on the first commercial machine built to handle a global RNAi rollout, as the sole owner of the innovation. And it should be big.

Patisiran — designed to silence messenger RNA and block the production of TTR protein before it is made — is number 6 on Clarivate’s list of blockbusters set to launch this year, with a 2022 sales forecast of $1.22 billion. Some of the peak sales estimates range significantly higher as analysts crunch the numbers on a disease that afflicts only about 30,000 people worldwide.

“What a feeling,” Maraganore tells me. “Having been for almost two decades fighting the good days and the bad days, with lots of challenges and near-death moments. It’s all about working hard to get something done.”

The writing on this landmark achievement has been on the regulatory wall since last September, when researchers scored a positive hit for the primary as well as all secondary endpoints in treating rare cases of hereditary ATTR amyloidosis with polyneuropathy.

Over the past 10 months, Alnylam has cruised along, picking up an accelerated priority review and breakthrough status at the FDA, a positive, early thumbs-up from European regulators and fast access in the UK. 

Behind the scenes, a gung-ho Maraganore has been setting the stage for a rapid global rollout, with new hires as the biotech plans to hustle it out ahead of a rival therapy at Ionis’ younger sister biotech Akcea — widely expected to play the role of distant second to patisiran. Maraganore reworked his collaboration deal with Sanofi to get full commercial rights to patisiran. Sanofi, in turn, took over commercial rights for fitusiran — an RNAi program for hemophilia, where it is now investing heavily.

With 700 staffers last year, the staff has now grown to 950, says Maraganore. It will be 1100 by the end of this year.

“Ten are in Tokyo,” he adds. “We’re building out Latin America and other countries. This is now going to be a global effort for Alnylam.”

Alnylam President Barry Greene is in charge of the commercial rollout for a drug that will now be known as Onpattro. And he’s already been out selling a value-based payment plan to US health insurers, looking to hit the ground running on the marketing campaign.

The list price was set at $450,000 per year for the some 3,000 patients diagnosed with the disease in the US, making it one of the most expensive new drugs in the country. That would translate to about $345,000 after rebates.

The CEO still keeps a clip of that Andy Pollack story by his desk. The newsprint is yellowed now, but it’s an ever-present reminder of the work that had to be done to survive the dark days that followed a period of exuberance as experts hailed the arrival of RNAi and its revolutionary, “cure-all” approach to disease.

The reality, as always, was much different.

Five by ’15 has now become 20 by ’20 — a mix of pipeline and marketed products with strategic focuses on top — as Alnylam looks to build up a portfolio of approved drugs that it can market itself. Maraganore wants to follow the examples of Genentech and Gilead to build a much bigger biotech that will have a lasting impact.

Alnylam’s success this year offers a chance to highlight the lengthy timelines required for birthing a major new therapeutic class of drugs. Watching one startup survive the entire pioneer-through-player process to emerge as the leader in the industry is a rare event. But in the past 2 years we’ve seen Spark Therapeutics land the first gene therapy OK in the US, while Kite and Novartis vaulted to the market with CAR-T.

And now Alnylam delivers for patients in RNAi. Maraganore says their new drug will hit the market in 48 hours.

Image: Alnylam CEO John Maraganore.Lane Turner/The Boston Globe via Getty Images

The best place to read Endpoints News? In your inbox.

Comprehensive daily news report for those who discover, develop, and market drugs. Join 48,100+ biopharma pros who read Endpoints News by email every day.

Free Subscription

Research Scientist - Immunology
Recursion Pharmaceuticals Salt Lake City, UT
Director of Operations
Atlas Venture Cambridge, MA

Visit Endpoints Careers ->