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

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

UP­DAT­ED: Boehringer nabs FDA's first in­ter­change­abil­i­ty des­ig­na­tion for its Hu­mi­ra com­peti­tor — but will it mat­ter?

The FDA late Friday awarded Boehringer Ingelheim the first interchangeability designation for its Humira biosimilar Cyltezo, meaning that when it launches in July 2023, pharmacists will be able to automatically substitute the Boehringer’s version for AbbVie’s mega-blockbuster without a doctor’s input.

The designation will likely give Boehringer, which first won approval for Cyltezo in 2017, the leg up on a crowded field of Humira competitors.

Bio­gen hit by ALS set­back with PhI­II fail­ure for tofersen — but fol­lows a fa­mil­iar strat­e­gy high­light­ing the pos­i­tive

Patients and analysts waiting to hear Sunday how Biogen’s SOD1-ALS drug tofersen fared in Phase III didn’t have to wait long for the top-line result they were all waiting for. The drug failed the primary endpoint on significantly improving the functional and neurologic decline of patients over 28 weeks as well as the extension period for continued observation.

In fact, there was very little difference in response.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,000+ biopharma pros reading Endpoints daily — and it's free.

Jeffrey Nau, Oyster Point Pharma CEO

FDA OKs an in­haled ver­sion of smok­ing ces­sa­tion drug Chan­tix — for a com­mon eye dis­ease

Oyster Point Pharma now has its first FDA-approved product — Tyrvaya. And the biotech has taken a unique route to get there by using an old drug with a storied past.

The New Jersey biotech announced this morning that the FDA has approved their nasal spray product for dry eye disease on Friday — the first nasal spray to be approved for the disease. The product’s active ingredient is 0.03 mg of varenicline, also known as smoking cessation aid Chantix.

Sheldon Koenig, Esperion CEO

Es­pe­ri­on gets out the bud­get ax, chop­ping 170 staffers as its big drug launch sput­ters

Esperion’s executive team spent years insisting that they had found the sweet spot in the market for their cholesterol drug. But that strategy has soured badly, and after struggling to sell its heart disease pill for more than a year, the biotech says it will cut about 40% of its staff over the next few weeks.

The layoffs will take place across the board, from sales and marketing to R&D, CEO Sheldon Koenig told Endpoints News on Monday. While the chief executive declined to elaborate on how many employees will be affected, an SEC filing stated that approximately 170 staffers are on the chopping block.

Two drug­mak­ers hit with PDU­FA date de­lays from FDA amid back­log of in­spec­tions

As the FDA is weighed down with more and more pandemic responsibilities, the agency is beginning to miss PDUFA dates with more frequency too. Two different companies on Monday said they received notices that the FDA has not completed their drug reviews on time.

The review of an NDA for Avadel Pharmaceuticals’ candidate treatment for narcolepsy is not coming this month, the company said, and the review of UCB’s BLA for bimekizumab, used to treat moderate to severe plaque psoriasis, will miss its target date as well.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,000+ biopharma pros reading Endpoints daily — and it's free.

Reshma Kewalramani, Vertex CEO (YouTube)

Ver­tex gets much-need­ed win with ‘ex­tra­or­di­nary’ first pa­tient re­sults on po­ten­tial di­a­betes cure

Vertex said Monday that the first patient dosed with its cell therapy for type 1 diabetes saw their need for insulin injections vanish almost entirely, a key early step in the decades-long effort to develop a curative treatment for the chronic disease.

The patient, who had suffered five potentially life-threatening hypoglycemic — or low blood sugar — episodes in the year before the therapy, was injected with synthetic insulin-producing cells. After 90 days, the patient’s new cells produced insulin steadily and ramped up their insulin production after a meal like normal cells do, as measured by a standard biomarker for insulin production.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,000+ biopharma pros reading Endpoints daily — and it's free.

Covid-19 vac­cine boost­ers earn big thumbs up, but Mod­er­na draws ire over world sup­ply; What's next for Mer­ck’s Covid pill?; The C-suite view on biotech; 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.

You may remember that at the beginning of this year, Endpoints News set a goal to go broader and deeper. We are still working towards that, and are excited to share that Beth Snyder Bulik will be joining us on Monday to cover all things pharma marketing. You can sign up for her weekly Endpoints MarketingRx newsletter in your reader profile.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,000+ biopharma pros reading Endpoints daily — and it's free.

Scott Struthers, Crinetics CEO

Cri­net­ics spins out ra­dio­phar­ma ef­forts in­to a new com­pa­ny, high­light­ing the grow­ing field­'s al­lure

Largely known for its nonpeptide small molecule research, Crinetics has been keeping its radiopharma work comparatively under wraps. But that changed Monday afternoon as the California biotech spun out a new company focused solely on the burgeoning field.

Crinetics launched Radionetics after the closing bell Monday, the company announced, seeding the new entity with $30 million raised from 5AM Ventures and Frazier Healthcare Partners. Radionetics will start with its own radiopharma-centric platform and a pipeline of 10 programs aimed at solid tumors.