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.”

 

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His­toric drug pric­ing re­forms pass; Pfiz­er ac­quires GBT; The long search for non-opi­oid pain drugs; 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.

The Endpoints Weekly has officially crossed the 60,000 mark on subscribers — thanks to all of your support. As the editorial team grows, we’ve been able to do a lot more, with many of those on display this week. Be sure to check out Lei Lei Wu’s deep dive on pain R&D. If you missed it, you may also rewatch her companion panel here.

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Gold for adults, sil­ver for in­fants: Pfiz­er's Pre­vnar 2.0 head­ed to FDA months af­ter Mer­ck­'s green light

Pfizer was first to the finish line for the next-gen pneumococcal vaccine in adults, but Merck beat its rival with a jab for children in June.

Now, two months after Merck’s 15-valent Vaxneuvance won the FDA stamp of approval for kids, Pfizer is out with some late-stage data on its 20-valent shot for infants.

Known as Prevnar 20 for adults, Pfizer’s 20vPnC will head to the FDA by the end of this year for an approval request in infants, the Big Pharma said Friday morning. Discussions with the FDA will occur first and more late-stage pediatric trials are expected to read out soon, informing the regulatory pathway in other countries and regions.

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No­var­tis re­ports two pa­tient deaths af­ter treat­ment with Zol­gens­ma

Two children with spinal muscular atrophy have died after receiving Novartis’ Zolgensma, a gene therapy designed as a one-time treatment for the rare fatal disease.

The deaths, which resulted from acute liver failure, occurred in Russia and Kazakhstan, Novartis confirmed in a statement to Endpoints News. Having notified health authorities across all the markets where Zolgensma is available, it will update the drug label “to specify that fatal acute liver failure has been reported,” a spokesperson wrote.

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House pass­es his­toric drug pric­ing re­forms, lin­ing up decades-in-the-mak­ing win for Biden and De­moc­rats

The US House of Representatives today voted along party lines (all Dems voted for it), 220-207 to pass new, wide-ranging legislation that will allow Medicare drug price negotiations for the first time ever, and cap seniors’ drug expenses to $2,000 per year and seniors’ insulin costs at $35 per month.

Setting up a major victory for President Joe Biden, representatives returned from their summer recess to pass the Inflation Reduction Act, even as many noted the bill would only modestly reduce inflation.

Senate Finance Committee Chair Ron Wyden (D-OR) (Francis Chung/E&E News/POLITICO via AP Images)

Sen­ate Fi­nance chair con­tin­ues his in­ves­ti­ga­tion in­to phar­ma tax­es with re­quests for Am­gen

Amgen is the latest pharma company to appear on the radar of Senate Finance Committee Chair Ron Wyden (D-OR), who is investigating the way pharma companies are using subsidiaries in low- or zero-tax countries to lower their tax bills.

Like its peers Merck, AbbVie and Bristol Myers Squibb, Wyden notes how Amgen uses its Puerto Rico operations to consistently pay tax rates that are substantially lower than the U.S. corporate tax rate of 21%, with an effective tax rate of 10.7% in 2020 and 12.1% in 2021.

FDA ap­proves sec­ond in­di­ca­tion for As­traZeneca and Dai­ichi's En­her­tu in less than a week

AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu scored its second approval in less than a week, this time for a subset of lung cancer patients.

Enhertu received accelerated approval on Thursday to treat adults with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, and who have already received a prior systemic therapy.

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J&J to re­move talc prod­ucts from shelves world­wide, re­plac­ing with corn­starch-based port­fo­lio

After controversially spinning out its talc liabilities and filing for bankruptcy in an attempt to settle 38,000 lawsuits, Johnson & Johnson is now changing up the formula for its baby powder products.

J&J is beginning the transition to an all cornstarch-based baby powder portfolio, the pharma giant announced on Thursday — just months after a federal judge ruled in favor of its “Texas two-step” bankruptcy to settle allegations that its talc products contained asbestos and caused cancer. An appeals court has since agreed to revisit that case.

CSL is gathering its four business units under a unified brand identity strategy (Credit: CSL company site)

CSL brings Se­qirus, Vi­for un­der par­ent um­brel­la brand in iden­ti­ty re­vamp

CSL is gathering its brands under the family name umbrella, renaming its vaccine and newly acquired nephrology specialty businesses with the parent initials.

CSL Seqirus and CSL Vifor join CSL Plasma and CSL Behring as the four now uniformly branded business units of the global biopharma. The Seqirus vaccine division was formed in 2015 with the combination of bioCSL and its purchase of Novartis’ flu vaccine business. CSL picked up Vifor Pharma late last year in an $11.7 billion deal for the nephrology, iron deficiency and cardio-renal drug developer.

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