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

Patrik Jonsson, the president of Lilly Bio-Medicines

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In just 8 days, from December 6 to December 14, the stock jumped from $7.88 to $12.70 — just under the initial $13 bid. There was no hard news about the company that would explain a rise like that tracking closely to the bid offer, raising the obvious question of whether insider info has leaked out to traders.

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For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
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A $1B-plus drug stum­bles in­to an­oth­er big PhI­II set­back -- this time flunk­ing fu­til­i­ty test -- as FDA hold re­mains in ef­fect for Ipsen

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Stephen Hahn, AP

The FDA has de­val­ued the gold stan­dard on R&D. And that threat­ens every­one in drug de­vel­op­ment

Bioregnum Opinion Column by John Carroll

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Over the last few years, biopharma has enjoyed an unprecedented loosening over just what it takes to clear that bar. Regulators are more willing to drop the second trial requirement ahead of an accelerated approval — particularly if they have an unmet medical need where patients are clamoring for a therapy.

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And they breathlessly reported every moment of the early morning dash.

In shuttering the city, triggering an exodus of masked residents who caught wind of the quarantine ahead of time, China signaled that they were prepared to take extreme actions to stop the spread of a virus that has claimed 17 lives, sickened many more and panicked people around the globe.

CNN helped illustrate how hard all that can be.

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Every few years, a public health crisis (think Ebola, Zika) spurred by a rogue pathogen triggers a small-biotech rally, as drugmakers emerge from the woodwork with ambitious plans to treat the mounting outbreak. In most cases, that enthusiasm never quite delivers.

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