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

John Hood [file photo]

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CEO Pascal Soriot via Getty Images

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