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.”

 

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Image: Shutterstock

Eli Lil­ly asks FDA to re­voke EUA for Covid-19 treat­ment

Eli Lilly on Friday requested that the FDA revoke the emergency authorization for its Covid-19 drug bamlanivimab, which is no longer as effective as a combo therapy because of a rise in coronavirus variants across the US.

“With the growing prevalence of variants in the U.S. that bamlanivimab alone may not fully neutralize, and with sufficient supply of etesevimab, we believe now is the right time to complete our planned transition and focus on the administration of these two neutralizing antibodies together,” Daniel Skovronsky, Lilly’s CSO, said in a statement.

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Mer­ck scraps their $425M Covid-19 drug in lat­est pan­dem­ic set­back

Seven months after paying $425 million cash to acquire it, Merck is scrapping a Covid-19 drug they hoped could provide one of the only treatments for severe hospitalized patients.

Merck’s decision comes after they faced significant and unexpected regulatory delays in getting the drug, known as MK-7110 or CD24Fc, across the finish line. The Big Pharma licensed the drug under the belief that it had already shown sufficient benefit in severe patients and they could help scale it up far faster than OncoImmune, its former owner, could. But in February, the company reported that the FDA insisted Merck run a new trial before seeking authorization.

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Severin Schwan, Roche CEO (Georgios Kefalas/Keystone via AP Images)

Look­ing to ce­ment its lead in packed MS mar­ket, Roche's Ocre­vus un­corks new da­ta in ear­ly-stage pa­tients

Among a positively jam-packed multiple sclerosis market, Roche’s Ocrevus has managed to stand out for what the Swiss drugmaker is calling the most successful launch in its long history. But in order to press its advantage, Ocrevus is looking to earlier-stage patients, and new interim data should help build its case there.

After 48 weeks on Roche’s Ocrevus, 85% of newly diagnosed primary progressing or relapsing MS patients without a history of disease modifying therapy posted no disease activity, including disease progression or relapse, according to interim data set to be presented this weekend at the virtual American Academy of Neurology meeting.

J&J faces CDC ad­vi­so­ry com­mit­tee again next week to weigh Covid-19 vac­cine risks

The CDC’s Advisory Committee on Immunization Practices punted earlier this week on deciding whether or not to recommend lifting a pause on the administration of J&J’s Covid-19 vaccine, but the committee will meet again in an emergency session next Friday to discuss the safety issues further.

The timing of the meeting likely means that the J&J vaccine will not return to the US market before the end of next week as the FDA looks to work hand-in-hand with the CDC to ensure the benefits of the vaccine still outweigh the risks for all age groups.

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Osman Kibar (Samumed, now Biosplice)

Os­man Kibar lays down his hand at Sa­mumed, step­ping away from CEO role as his once-her­ald­ed an­ti-ag­ing biotech re­brands

Samumed made quite the entrance back in 2016, when it launched with some anti-aging programs and a whopping $12 billion valuation. That level of fanfare was nowhere to be found on Thursday, when the company added another $120 million to its coffers and quietly changed its name to Biosplice Therapeutics.

Why the sudden rebrand?

“We did that for obvious reasons,” CFO and CBO Erich Horsley told Endpoints News. “The name Biosplice echoes our science much more than Samumed does.”

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Ex­clu­sive in­ter­view: Pe­ter Marks on why full Covid-19 vac­cine ap­provals could be just months away

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, took time out of his busy schedule last Friday to discuss with Endpoints News all things related to his work regulating vaccines and the pandemic.

Marks, who quietly coined the name “Operation Warp Speed” before deciding to stick with his work regulating vaccines at the FDA rather than join the Trump-era program, has been the face of vaccine regulation for the FDA throughout the pandemic, and is usually spotted in Zoom meetings seated in front of his wife’s paintings.

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Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

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Pascal Soriot (AstraZeneca via YouTube)

Af­ter be­ing goad­ed to sell the com­pa­ny, Alex­ion's CEO set some am­bi­tious new goals for in­vestors. Then Pas­cal So­ri­ot came call­ing

Back in the spring of 2020, Alexion $ALXN CEO Ludwig Hantson was under considerable pressure to perform and had been for months. Elliott Advisers had been applying some high public heat on the biotech’s numbers. And in reaching out to some major stockholders, one thread of advice came through loud and clear: Sell the company or do something dramatic to change the narrative.

In the words of the rather dry SEC filing that offers a detailed backgrounder on the buyout deal, Alexion stated: ‘During the summer and fall of 2020, Alexion also continued to engage with its stockholders, and in these interactions, several stockholders encouraged the company to explore strategic alternatives.’

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