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

Un­pack­ing the Aduhelm de­ci­sion, Ver­tex's half full glass, a $525M J&J breakup, and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

By now you have surely read about the FDA’s controversial approval of Biogen’s Alzheimer’s drug and all its reverberations. But I’d still recommend checking out the meaty recap below to make sure you didn’t miss all the angles that the Endpoints team has covered. If you’d rather look ahead, look no further than our three-day virtual panels next week at BIO, where we will discuss what the new normal means for every part of the industry.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,100+ biopharma pros reading Endpoints daily — and it's free.

What does a clear ma­jor­i­ty of the bio­phar­ma in­dus­try think of the FDA ap­proval of ad­u­canum­ab? 'Hor­ri­fy­ing' 'Dan­ger­ous' 'Con­fus­ing' 'Dis­as­ter'

Over the years, we’ve become used to seeing a consensus emerge early in our industry polls at Endpoints News. And when we took the pulse of drug hunters on the heels of a controversial FDA approval for aducanumab this week, it became immediately apparent that the vast majority of our readers — heavily concentrated among biopharma staffers and execs — were incensed by what they had just witnessed.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,100+ biopharma pros reading Endpoints daily — and it's free.

David Knopman (Mayo Clinic via YouTube)

A sec­ond ad­comm mem­ber aban­dons his post in af­ter­math of con­tro­ver­sial ad­u­canum­ab de­ci­sion

As the fallout from the FDA’s approval of Alzheimer’s med aducanumab grows, a second member of the adcomm overseeing that drug’s review has walked away. But even with two experts now having resigned from that committee in protest, is there enough broad-level outrage to prevent another aducanumab from getting approved?

The FDA on Wednesday lost another member of its Peripheral and Central Nervous System Drugs Advisory Committee as Mayo Clinic neurologist David Knopman hit the exit over the agency’s decision to approve Biogen’s Alzheimer’s drug Aduhelm despite the committee’s near-unanimous vote against it.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,100+ biopharma pros reading Endpoints daily — and it's free.

Aaron Kesselheim (Scott Eisen/AP Images for AIDS Healthcare Foundation)

Har­vard’s Aaron Kessel­heim re­signs from ex­pert pan­el in wake of ad­u­canum­ab OK, blast­ing FDA for ‘worst drug ap­proval de­ci­sion in re­cent U.S. his­to­ry'

A third member of the FDA’s Peripheral and Central Nervous System Drugs Advisory Committee has resigned in the wake of Biogen’s controversial Aduhelm approval, slamming the agency as he left and further deepening the controversy surrounding the decision.

Harvard University professor Aaron Kesselheim quit in protest Thursday afternoon, calling the Aduhelm OK “probably the worst drug approval decision in recent U.S. history.” Kesselheim follows both Joel Perlmutter, a neurologist from Washington University in St. Louis, and David Knopman, a neurologist from the Mayo Clinic, out the door.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,100+ biopharma pros reading Endpoints daily — and it's free.

Janet Woodcock, acting FDA commissioner, at Thursday's Senate Appropriations hearing (Bill Clark/CQ Roll Call via AP Images)

Sen­a­tors lam­bast new Alzheimer’s drug’s price but give Janet Wood­cock a free pass on the ap­proval de­ci­sion

Senate Finance Democrats took aim at Biogen’s pricey new Alzheimer’s drug on Thursday, but members on both sides of the aisle at a separate appropriations hearing didn’t question acting FDA commissioner Janet Woodcock on the approval.

“I was appalled that Biogen priced their Alzheimer’s drug approved by the FDA at $56,000 per year — I’m not going to debate whether this is effective or not, but it’s double the household median income for Michiganders over the age of 65,” Sen. Debbie Stabenow (D-MI) said at the finance hearing.

FDA au­tho­rizes about 10M J&J vac­cine dos­es, trash­es 60M more from trou­bled Emer­gent plant

The FDA on Friday released about 10 million doses of J&J’s vaccine for use, and disposed of another 60 million doses that were manufactured at the now-shuttered Emergent BioSolutions facility in Baltimore where cross-contamination occurred.

The agency said it’s not yet ready to allow the Emergent plant to be included in the J&J EUA, but that may occur soon. FDA came to the decision to authorize some of the doses after reviewing facility records and quality testing results.

Paul Hudson, Sanofi CEO (Eric Piermont/AFP via Getty Images)

Months af­ter FDA re­jec­tion, Sanofi touts piv­otal win for rare dis­ease drug su­tim­limab as it preps to re­file

One of the pillar drugs of Sanofi’s $11.6 billion pickup of Bioverativ hit a big setback late last year when the FDA sent its application for approval back. Now, as Sanofi gears up to resubmit the drug for review, the drugmaker is touting pivotal data it hopes will help take it over the finish line.

Sanofi’s sutimlimab nailed all three of its primary endpoints in its Phase III CADENZA study for patients with cold agglutinin disease, a rare disorder that can cause severe anemia, without a recent history of blood transfusion, the French drugmaker said Friday. The topline results will be presented at this weekend’s virtual EHA meeting.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,100+ biopharma pros reading Endpoints daily — and it's free.

Reshma Kewalramani, Vertex CEO (BIO via YouTube)

UP­DAT­ED: Ver­tex strikes out on its lat­est big shot at a rare ge­net­ic dis­ease. But they're go­ing to keep on swing­ing

It’s been several months since Vertex culled one of its small molecules for alpha-1 antitrypsin deficiency (AATD), taking a big hit after evidence of liver damage surfaced in a key Phase II trial. Now we learned that the company has whiffed on its second shot, and there’s nothing left in the clinic to treat the rare genetic disease — but that won’t stop it from trying.

Despite avoiding the safety issues that plagued the last candidate, Vertex $VRTX is taking the axe to VX-864 after Phase II results revealed the magnitude of the drug’s response is “unlikely to translate into substantial clinical benefit.” As a result of the news, the company’s stock fell 12.5% after hours.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 109,100+ biopharma pros reading Endpoints daily — and it's free.

Bris­tol My­er­s' CAR-T Breyanzi busts out a win in ear­li­er-line lym­phoma, po­ten­tial­ly crack­ing open an ex­pand­ed mar­ket

Despite being third to the field in B cell lymphoma, Bristol Myers Squibb has repeatedly argued its CAR-T Breyanzi could have the juice to overtake its older competitors. Going into earlier lines of therapy may be the golden ticket on that front, and now Breyanzi has a late-stage win to back up that effort.

Bristol Myers’s Breyanzi beat out physicians’-choice salvage therapy followed by high-dose chemo and a stem cell transplant — what the drugmaker called a “gold standard treatment” — in second-line patients with relapsed or refractory large B cell lymphoma, according to topline data from the Phase III TRANSFORM study released Thursday.