Al­ny­lam achieves break­through RNAi suc­cess as PhI­II patisir­an study hits all goals, shares soar

Al­ny­lam in­vestors $AL­NY can now start breath­ing again.

The big Cam­bridge, MA-based biotech says that their Phase III study of patisir­an — part­nered with Sanofi — scored a pos­i­tive hit for the pri­ma­ry as well as all sec­ondary end­points in treat­ing rare cas­es of hered­i­tary AT­TR amy­loi­do­sis with polyneu­ropa­thy.


The score sets up Al­ny­lam’s first new drug ap­pli­ca­tion with the FDA be­fore the end of this year with a Eu­ro­pean fil­ing fol­low­ing soon af­ter, while Sanofi gears up for a slate of ap­pli­ca­tions around the globe.

Shares of Al­ny­lam shot up more than 20% in pre-mar­ket trad­ing Wednes­day, as the com­pa­ny added to a mar­ket cap that start­ed to­day at just un­der $7 bil­lion. But it didn’t stop there, with shares up 32% in ear­ly trad­ing as ex­cite­ment about the news spread fast. By mid-af­ter­noon, the stock was up 49%, worth more than $3 bil­lion in mar­ket cap.

Al­ny­lam’s gung-ho CEO John Maraganore, who has steered the com­pa­ny through calm seas and mael­stroms for more than a decade as he pi­o­neered one of the biggest RNA ven­tures in the in­dus­try, was clear­ly beam­ing as the in­dus­try ea­ger­ly pounced on the news of the first pos­i­tive Phase III study for an RNAi drug. He said:

This mo­ment is the cul­mi­na­tion of a 15-year jour­ney of tire­less work by count­less con­trib­u­tors who have over­come enor­mous sci­en­tif­ic and busi­ness chal­lenges to make RNAi ther­a­peu­tics a re­al­i­ty.

Sanofi, which bet big on Al­ny­lam when it in­vest­ed $700 mil­lion in­to the com­pa­ny more than three years ago, al­so cheered the re­sults.

The suc­cess for patisir­an comes af­ter some big clin­i­cal set­backs for Al­ny­lam, which has been dogged for years over the safe­ty is­sues raised by RNAi ther­a­pies. About 8 years ago big phar­ma large­ly bailed on RNAi, dis­turbed by the de­vel­op­ment chal­lenges and the time it would take to de­liv­er ma­jor new ther­a­pies. But Maraganore nev­er flinched, in­sist­ing through­out that his com­pa­ny could de­liv­er on its pipeline promis­es.

All we know right now is what the top line re­sults are.

The pri­ma­ry end­point for the study was the change from base­line in the mod­i­fied neu­ropa­thy im­pair­ment score, where re­searchers reg­is­tered a sta­tis­ti­cal­ly sig­nif­i­cant re­sult. Pa­tients on patisir­an al­so scored an im­prove­ment in their qual­i­ty of life. And there were hits on all 5 sec­on­daries:

NIS-W, the sub­do­main of mNIS+7 as­sess­ing mus­cle strength;

Rasch-built Over­all Dis­abil­i­ty Scale (R-ODS), a pa­tient re­port­ed out­come mea­sure of dai­ly liv­ing and dis­abil­i­ty;

10-me­ter walk test, as­sess­ing gait speed;

Mod­i­fied body mass in­dex (mB­MI), as­sess­ing nu­tri­tion­al sta­tus; and

COM­PASS-31, a ques­tion­naire to as­sess au­to­nom­ic symp­toms.

In ad­di­tion, while de­tails are lack­ing, the safe­ty pro­file looked good. Pa­tients in both groups ex­pe­ri­enced ad­verse events, but the drug arm com­pared fa­vor­ably with what we know about the place­bo group. Paul Mat­teis at Leerink not­ed:

In the wake of the re­cent fi­tusir­an set­back – and al­so the dis­con­tin­u­a­tion of re­vusir­an last fall – the pos­i­tive patisir­an re­sult with seem­ing­ly clean safe­ty is like­ly to im­prove sen­ti­ment sig­nif­i­cant­ly. Specif­i­cal­ly, the mor­tal­i­ty rate in the patisir­an arm (4.7%) was low­er than that seen on place­bo (7.8%); giv­en the small N it’s de­bat­able whether or not this con­sti­tutes a true im­prove­ment, but in any case it’s very en­cour­ag­ing with re­spect to RNAi safe­ty. Iron­i­cal­ly, more re­cent set­backs for AL­NY (re­vusir­an and then fi­tusir­an) have come from next-gen RNAi com­pounds that do not uti­lize the old­er, lipid­nanopar­ti­cle tech­nol­o­gy, which is the case for patisir­an. But even de­spite this dif­fer­ence, we ex­pect the re­sult this morn­ing to read pos­i­tive­ly on the plat­form and tech­nol­o­gy over­all.

But it won’t help Io­n­is, which has a com­pet­ing ther­a­py. That drug is now be­ing con­sid­ered an al­so ran against Al­ny­lam’s ther­a­py, with some an­a­lysts ex­pect­ing patisir­an to claim an 80% mar­ket share. Io­n­is stock $IONS plunged 10% this morn­ing.

Maraganore, this year’s BIO chair­man, is one of the most fa­mil­iar fig­ures in the biotech world. And he had plen­ty of sup­port to­day from the cheer­ing sec­tion on Twit­ter.

“This is a sig­nif­i­cant mile­stone that sup­ports our be­lief that RNAi ther­a­peu­tics have the po­ten­tial to be­come an in­no­v­a­tive new class of med­i­cines for pa­tients with rare ge­net­ic dis­eases,” said Elias Zer­houni, the pres­i­dent of R&D at Sanofi. “The APOL­LO da­ta sug­gest that patisir­an could help im­prove the lives of peo­ple liv­ing with hAT­TR amy­loi­do­sis with polyneu­ropa­thy, a pa­tient pop­u­la­tion in ur­gent need of ad­di­tion­al treat­ment op­tions. We look for­ward to work­ing with Al­ny­lam to make patisir­an avail­able around the globe as quick­ly as pos­si­ble.”

 

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

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