Al­ny­lam spot­lights just how good the ef­fi­ca­cy da­ta are for givosir­an — tamp­ing down on safe­ty con­cerns

Al­ny­lam $AL­NY took an­oth­er turn on its tran­si­tion lap to a ful­ly fledged com­mer­cial biotech to­day, post­ing its de­tailed — and very promis­ing — ef­fi­ca­cy da­ta for their RNAi drug givosir­an while hop­ing to tamp down the fret­ting over safe­ty is­sues that spoiled their ear­li­er top-line an­nounce­ment.

We knew go­ing in­to the Eu­ro­pean As­so­ci­a­tion for the Study of the Liv­er meet­ing in Vi­en­na that the drug had a great p val­ue — now backed up by a 90% me­di­an re­duc­tion in at­tacks of acute he­pat­ic por­phyr­ia, a painful and de­bil­i­tat­ing ill­ness with no cur­rent­ly ap­proved ther­a­pies. Half of the pa­tients end­ed at­tack free, which would make this a no-brain­er for reg­u­la­tors.

What rat­tled some of the an­a­lysts last time was that the rate of se­ri­ous ad­verse events in the drug arm was more than twice what was seen in the place­bo group. A se­ri­ous safe­ty sig­nal could ham­per or tor­pe­do any drug, and in­deed we learned that sev­er­al of the pa­tients ex­pe­ri­enced se­ri­ous is­sues trig­gered by the ther­a­py. Specif­i­cal­ly, this in­volved cas­es of chron­ic kid­ney dis­ease, pyrex­ia and ab­nor­mal liv­er func­tion test.

Al­ny­lam CEO John Maraganore, though, says that with this drug for this dis­ease in these pa­tients, it will pass muster to soon be­come Al­ny­lam’s sec­ond ap­proved ther­a­py — a land­mark event for a com­pa­ny that has be­come a stan­dard-set­ter for many of the de­vel­op­ment-stage com­pa­nies hop­ing to tran­si­tion in­to mar­ket­ing one day.

Al­ny­lam CEO John Maraganore Get­ty Im­ages

Click on the im­age to see the full-sized ver­sion


“This is a dis­ease that’s about as bad as it gets,” Maraganore told me in a pre­view of to­day’s pre­sen­ta­tion. “It is a ter­ri­ble, ter­ri­ble dis­ease, and ob­vi­ous­ly when you look at the ben­e­fit it’s pret­ty over­whelm­ing.”

Maraganore knows that 2 cas­es of CKD won’t go un­no­ticed by any­one, but in bal­anc­ing the risk/ben­e­fit, he says there’s no doubt that the drug will get a green light. Be­sides, he adds, these pa­tients typ­i­cal­ly have a high risk of kid­ney dis­ease and liv­er is­sues, which reg­u­la­tors will cer­tain­ly take in­to ac­count.

As for pa­tients, he says, the da­ta speak for them­selves, with 93 of 94 pa­tients go­ing on to en­roll in the ex­ten­sion pe­ri­od of the study.

“We couldn’t be more hap­py about the da­ta,” he adds. “If my daugh­ter had this dis­ease I wouldn’t hes­i­tate for a nanosec­ond” to get her on the drug. And then he threw his moth­er and him­self in­to that sce­nario. 

Every­body gets the drug.

That has Jef­feries? Mau­ry Ray­croft fore­cast­ing $600 mil­lion in peak sales by 2030. He adds:

For us, there were no sur­pris­es at EASL, and as a re­sult we are more con­fi­dent in gi­vo’s over­all pro­file and po­ten­tial. The ph.III in­ves­ti­ga­tor and AL­NY be­lieve the drug can be used broad­ly in AHP; add’ly, both AL­NY and the in­ves­ti­ga­tor an­tic­i­pate re­sults will con­tin­ue to im­prove.

Some of the ob­servers ear­li­er al­so weren’t too hap­py about a mixed set of sec­ondary end­points, with the ther­a­py scor­ing for sev­er­al bio­mark­ers of the dis­ease but falling short of sta­tis­ti­cal sig­nif­i­cance on sec­on­daries like pain and fa­tigue and nau­sea, what pa­tients are feel­ing.

Maraganore con­ced­ed those points but coun­tered that you don’t have to hit every sec­ondary to get an ap­proval — true enough — and that a set of pa­tient-re­port­ed out­comes in­di­cat­ed that 89% re­port­ed an im­prove­ment on ther­a­py com­pared to 37% on place­bo.

Maraganore is like­ly right about the caveats. No ther­a­py is per­fect, and reg­u­la­tors will bend over back­wards on side ef­fects if they can get a treat­ment for this dis­ease. That leaves Al­ny­lam com­ing out of EASL with a time­line that an­tic­i­pates an ap­proval by this time next year.

As of now, they’re odds-on fa­vorites for an ap­proval.


Im­age: Kristof­fer Trip­plaar for SIPA AP

Cell and Gene Con­tract Man­u­fac­tur­ers Must Em­brace Dig­i­ti­za­tion

The Cell and Gene Industry is growing at a staggering 30% CAGR and is estimated to reach $14B by 20251. A number of cell, gene and stem cell therapy sponsors currently have novel drug substances and products and many rely on Contract Development Manufacturing Organizations (CDMO) to produce them with adherence to stringent regulatory cGMP conditions. Cell and gene manufacturing for both autologous (one to one) and allogenic (one to many) treatments face difficult issues such as: a complex supply chain, variability on patient and cellular level, cell expansion count and a tight scheduling of lot disposition process. This complexity affects quality, compliance and accountability in the entire vein-to-vein process for critically ill patients.

A lab technician works during research on coronavirus at Johnson & Johnson subsidiary Janssen Pharmaceutical in Beerse, Belgium, Wednesday, June 17, 2020. (Virginia Mayo/AP Images)

End­points News ranks all 28 play­ers in the Covid-19 vac­cine race. Here's how it stacks up to­day

The 28 players now in or close to the clinical race to get a Covid-19 vaccine over the finish line are angling for a piece of a multibillion-dollar market. And being first — or among the leaders — will play a big role in determining just how big a piece.

Endpoints News writer Nicole DeFeudis has posted a snapshot of all the companies, universities and hospital-based groups now racing through the clinic, ranking them according to their place in the pipeline as well as the latest remarks available on timelines. And we’ll keep this lineup updated right through the end of the year, as the checkered flags start to fall, possibly as early as October.

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Phase III read­outs spell dis­as­ter for Genen­tech’s lead IBD drug

Roche had big plans for etrolizumab. Eyeing a hyper-competitive IBD and Crohn’s market where they have not historically been a player, the company rolled out 8 different Phase III trials, testing the antibody for two different uses across a range of different patient groups.

On Monday, Roche released results for 4 of those studies, and they mark a decided setback for both the Swiss pharma and their biotech sub Genentech, potentially spelling an end to a drug they put over half-a-decade and millions of dollars behind.

Bayer's Marianne De Backer with Endpoints founder John Carroll, Endpoints@JPM20 (Jeff Rumans for Endpoints News)

UP­DAT­ED: Hunt­ing a block­buster, Bay­er forges an $875M-plus M&A deal to ac­quire women’s health biotech

Bayer has dropped $425 million in cash on its latest women’s health bet, bringing a UK biotech and its non-hormonal menopause treatment into the fold.

KaNDy Therapeutics had its roots in GlaxoSmithKline, which spun out several neuroscience drugs into NeRRe Therapeutics back in 2012. Five years later the team created a new biotech to focus solely on NT-814 — which they considered “one of the few true innovations in women’s health in more than two decades.”

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Eric Shaff (Seres)

UP­DAT­ED: Af­ter a 4-year so­journ, strug­gling mi­cro­bio­me pi­o­neer Seres claims a break­out PhI­II come­back. And shares re­spond in fren­zied spike

Almost exactly 4 years ago, Seres Therapeutics $MCRB experienced one of those soul-crunching failures that can raise big questions about a biotech’s future. Out front in their pursuit of a gut punch to C. difficile infection (CDI), the Phase II test was a flat failure, and investors wiped out a billion dollars of equity value that never returned in the years that followed.

Seres, though, pressed ahead, changing out CEOs a year ago — bidding Merck vet Roger Pomerantz farewell from the C suite — and pushing through a Phase III, hoping that amping up the dosage would make the key difference. And this morning, they unveiled a claim that they had aced the Phase III and positioned themselves for a run at a landmark FDA OK.

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Michel Vounatsos, Biogen CEO (via YouTube)

Bio­gen scores a pri­or­i­ty re­view for its Alzheimer's drug ad­u­canum­ab, mov­ing one gi­ant leap for­ward in its con­tro­ver­sial quest

Biogen scored a big win at the FDA today as regulators accepted their application for the controversial Alzheimer’s drug aducanumab and gave it a priority review.

The PDUFA date is March 7, 2021.

Significantly, Biogen says it did not use its priority review voucher to win special treatment at the FDA. The agency handed that out gratis.

That’s the ideal scenario Biogen was looking for as disappointed analysts wondered aloud about the delayed application earlier in the year.

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Robert Gould, Fulcrum Therapeutics CEO

Ful­crum stum­bles in PhII of old GSK drug, send­ing shares tum­bling

Investors are selling off shares of Fulcrum Therapeutics $FULC after their lead drug failed in a Phase II trial.

The company, founded three years ago on new research techniques such as CRISPR screening, isolated a gene called DUX4 they believed to have a central role in facioscapulohumeral muscular dystrophy, where patients’ muscle dies and is replaced by fat. And to target it, they licensed a GlaxoSmithKline drug that had failed as a cardio drug.

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Eisai moves to 200 Metro Blvd. by late 2021 (ON3)

Ei­sai is cre­at­ing a new US cor­po­rate, R&D HQ in Roche’s old Nut­ley, NJ cam­pus

Eight years after Roche pulled up stakes from Nutley, NJ in a major R&D reorganization, Japan’s Eisai is moving its US corporate and research hub into their old campus.

Now the ON3 property, Eisai — a longtime Biogen partner focused on neurodegenerative disorders like Alzheimer’s — will bring together a staff of up to 1,200 employees. And execs are pitching the move to the New Jersey campus as a cultural game-changer.

Bing Li, Debra Yu and Konstantin Poukalov, LianBio

Per­cep­tive births its first in-house start­up — and it's a Chi­na play

Perceptive Advisors is going to China.

The decision dates back two years, chief investment officer Adam Stone tells Endpoints News, when the firm began to figure out how it can, in hedge fund-speak, strategically increase its exposure to a growing biopharma market poised to be a key geographic area in the next several decades. It was a bit of a blindspot for Perceptive, he admits.

As “globalized scientist-investors, we just couldn’t afford to have that blindspot in place,” he says.