Al­ny­lam shores up en­thu­si­asm for givosir­an with ear­ly dataset ahead of cru­cial PhI­II read­out

In the run-up to top-line re­sults from a cru­cial Phase III for its sec­ond RNAi drug, Al­ny­lam has so­lid­i­fied an ear­ly set of safe­ty and ef­fi­ca­cy num­bers for givosir­an’s da­ta pack­age — part of a rolling sub­mis­sion at the FDA.

Re­sults from the Phase I, which we first heard about last April, sug­gest that month­ly in­jec­tions of givosir­an re­duced the num­ber of at­tacks in pa­tients with acute he­pat­ic por­phyr­ia by up to 79%, ac­cord­ing to a new pa­per in the New Eng­land Jour­nal of Med­i­cine. The us­age of hemin, an in­fu­sion cur­rent­ly used to treat these at­tacks, al­so dropped by 83% com­pared to place­bo, the com­pa­ny added.

Source: NE­JM

Click on the im­age to see the full-sized ver­sion

The key tar­get here is the ALAS1 mes­sen­ger RNA, or delta aminole­vulin­ic acid syn­thase 1, which leads to ac­cu­mu­la­tion of the tox­ic metabo­lites aminole­vulin­ic acid (ALA) — be­lieved to be the pri­ma­ry dis­ease trig­ger — and por­pho­bilino­gen (PBG). That leads to “acute de­bil­i­tat­ing neu­ro­vis­cer­al at­tacks and, in some pa­tients, dis­abling chron­ic symp­toms.”

Givosir­an brought all of them to nor­mal lev­els and kept it there, with a mean max­i­mum re­duc­tion of over 90%.

While promis­ing, these re­sults will have to be borne out by the on­go­ing PhI/II open-la­bel ex­ten­sion and Phase III stud­ies, es­pe­cial­ly con­sid­er­ing that the at­tack re­duc­tion da­ta are based on 6 pa­tients as­signed to givosir­an in one of three parts of this 40-pa­tient study.

Part C of the tri­al al­so ze­roed in on acute in­ter­mit­tent por­phyr­ia, “the most com­mon sub­type of AHP where pa­tients ex­pe­ri­ence re­cur­rent, in­ca­pac­i­tat­ing, neu­ro­vis­cer­al at­tacks re­quir­ing hos­pi­tal­iza­tion or ur­gent med­ical at­ten­tion,” ac­cord­ing to Eliane Sardh of the Karolin­s­ka In­sti­tutet, the lead au­thor of the NE­JM pa­per.

In terms of safe­ty — a his­toric con­cern for Al­ny­lam’s RNAi drugs — in­ves­ti­ga­tors doc­u­ment­ed se­ri­ous ad­verse events in 6 pa­tients who re­ceived givosir­an through­out the tri­al, in­clud­ing a fa­tal case of he­m­or­rhag­ic pan­cre­ati­tis con­sid­ered un­like­ly re­lat­ed to the drug. Oth­er com­mon ad­verse ef­fects in­clude na­sopharyn­gi­tis, ab­dom­i­nal pain and di­ar­rhea.

“There was no clear dif­fer­ence in the pro­por­tion of pa­tients who re­port­ed ad­verse events and se­vere ad­verse events be­tween the place­bo group and the givosir­an group, and there was no clear re­la­tion­ship be­tween givosir­an dose and the in­ci­dence of ad­verse events,” the NE­JM pa­per not­ed.

As­sum­ing pos­i­tive re­sults in the Phase III, Al­ny­lam aims to sub­mit full clin­i­cal sec­tions in mid-2019 for its rolling NDA af­ter drop­ping ear­li­er plans for an ac­cel­er­at­ed ap­proval.

Nick Leschly via Getty

UP­DAT­ED: Blue­bird shares sink as an­a­lysts puz­zle out $1.8M stick­er shock and an un­ex­pect­ed de­lay

Blue­bird bio $BLUE has un­veiled its price for the new­ly ap­proved gene ther­a­py Zyn­te­glo (Lenti­Glo­bin), which came as a big sur­prise. And it wasn’t the on­ly un­ex­pect­ed twist in to­day’s sto­ry.

With some an­a­lysts bet­ting on a $900,000 price for the β-tha­lassemia treat­ment in Eu­rope, where reg­u­la­tors pro­vid­ed a con­di­tion­al ear­ly OK, blue­bird CEO Nick Leschly said Fri­day morn­ing that the pa­tients who are suc­cess­ful­ly treat­ed with their drug over 5 years will be charged twice that — $1.8 mil­lion — on the con­ti­nent. That makes this drug the sec­ond most ex­pen­sive ther­a­py on the plan­et, just be­hind No­var­tis’ new­ly ap­proved Zol­gens­ma at $2.1 mil­lion, with an­a­lysts still wait­ing to see what kind of pre­mi­um can be had in the US.


Glob­al Blood Ther­a­peu­tics poised to sub­mit ap­pli­ca­tion for ac­cel­er­at­ed ap­proval, with new piv­otal da­ta on its sick­le cell dis­ease drug

Global Blood Therapeutics is set to submit an application for accelerated approval in the second-half of this year, after unveiling fresh data from a late-stage trial that showed just over half the patients given the highest dose of its experimental sickle cell disease drug experienced a statistically significant improvement in oxygen-wielding hemoglobin, meeting the study's main goal.

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News­mak­ers at #EHA19: Re­gen­eron, Ar­Qule track progress on re­sponse rates

Re­gen­eron’s close­ly-watched bis­pe­cif­ic con­tin­ues to ring up high re­sponse rates

Re­gen­eron’s high-pro­file bis­pe­cif­ic REGN1979 is back in the spot­light at the Eu­ro­pean Hema­tol­ogy As­so­ci­a­tion sci­en­tif­ic con­fab. And while the stel­lar num­bers we saw at ASH have erod­ed some­what as more blood can­cer pa­tients are eval­u­at­ed, the re­sponse rates for this CD3/CD20 drug re­main high.

A to­tal of 13 out of 14 fol­lic­u­lar lym­phomas re­spond­ed to the drug, a 93% ORR, down from 100% at the last read­out. In 10 out of 14, there was a com­plete re­sponse. In dif­fuse large B-cell lym­phoma the re­sponse rate was 57% among pa­tients treat­ed at the 80 mg to 160 mg dose range. They were all com­plete re­spons­es. And 2 of these Cars were for pa­tients who had failed CAR-T ther­a­py.

Gene ther­a­pies seize the top of the list of the most ex­pen­sive drugs on the plan­et — and that trend has just be­gun

Anyone looking for a few simple reasons why the gene therapy field has caught fire with the pharma giants need only look at the new list of the 10 most expensive therapies from GoodRx.

Two recently approved gene therapies sit atop this list, with Novartis’ Zolgensma crowned the king of the priciest drugs at $2.1 million. Right below is Luxturna, the $850,000 pioneer from Spark, which Roche is pushing hard to acquire as it adds a gene therapy group to the global mix.

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Neil Woodford, Woodford Investment Management via YouTube

Un­der siege, in­vest­ment man­ag­er Wood­ford faces an­oth­er in­vest­ment shock

Em­bat­tled UK fund man­ag­er Neil Wood­ford — who has con­tro­ver­sial­ly blocked in­vestors from pulling out from his flag­ship fund to stem the blood­let­ting, af­ter a slew of dis­ap­point­ed in­vestors fled fol­low­ing a se­ries of sour bets — is now pay­ing the price for his ac­tions via an in­vestor ex­o­dus on an­oth­er fund.

Har­g­reaves Lans­down, which has in the past sold and pro­mot­ed the Wood­ford funds via its re­tail in­vest­ment plat­form, has re­port­ed­ly with­drawn £45 mil­lion — its en­tire po­si­tion — from the in­vest­ment man­ag­er’s In­come Fo­cus Fund.

Search­ing for the next block­buster to fol­low Darza­lex, J&J finds a $150M an­ti-CD38 drug from part­ner Gen­mab

Now that J&J and Genmab have thrust Darzalex onto the regulatory orbit for first-line use in multiple myeloma, the partners are lining up a deal for a next-gen follow-on to the leading CD38 drug.

Janssen — J&J’s biotech unit — has its eyes on HexaBody-CD38, a preclinical compound generated on Genmab’s tech platform designed to make drugs more potent via hexamerization.

Genmab is footing the bill on studies in multiple myeloma and diffuse large B-cell lymphoma; once it completes clinical proof of concept, Janssen has the option to license the drug for a $150 million exercise fee. There’s also $125 million worth of milestones in play.

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Ab­b­Vie touts new da­ta for Hu­mi­ra suc­ces­sor; Gilead inks dis­cov­ery deal

→ Ab­b­Vie is tout­ing new pos­i­tive da­ta com­par­ing their ag­ing block­buster Hu­mi­ra with their hoped-for block­buster upadac­i­tinib. Over 48 weeks a larg­er pro­por­tion of pa­tients tak­ing the ex­per­i­men­tal drug ex­pe­ri­enced clin­i­cal re­mis­sion than in the con­trol arm with Hu­mi­ra. Their drug brought in $20 bil­lion last year, top­ping the scales in the num­ber 1 slot.

→ Gilead has turned to Van­cou­ver-based Ab­Cellera for its lat­est dis­cov­ery deal. Ab­Cellera will use its know-how in “sin­gle-cell screen­ing of nat­ur­al im­mune sources” to find an­ti­body can­di­dates for Gilead to pur­sue in the in­fec­tious dis­ease field. The deal in­cludes an up­front and mile­stones.

Turns out, Rudy Tanzi did­n't see much of a sto­ry about a hid­den link be­tween En­brel and Alzheimer's ei­ther

The Wash­ing­ton Post man­aged to whip up the quick­est in­dus­try con­sen­sus I’ve ever seen that one of its re­porters was pur­vey­ing overblown non­sense with a sto­ry that Pfiz­er was sit­ting on da­ta sug­gest­ing that En­brel could be an ef­fec­tive treat­ment for Alzheimer’s. 

In cov­er­ing that bit of an­ti-Big Phar­ma fan­ta­sy — there are lots of rea­sons to go af­ter phar­ma, but this piece was lu­di­crous — I not­ed com­ments in the sto­ry from some promi­nent peo­ple in the field crit­i­ciz­ing Pfiz­er for not pub­lish­ing the da­ta. I sin­gled out Rudy Tanzi at Har­vard and then ap­plied some added crit­i­cism for the things he’s done to hype — in my opin­ion — high­ly ques­tion­able as­sump­tions. You can see it in the link. 

Adding mar­quee in­vestors, Black­Thorn bags $76M to back an AI-dri­ven strat­e­gy for pre­ci­sion neu­ro med­i­cine

As ar­ti­fi­cial in­tel­li­gence and ma­chine learn­ing loom ever larg­er in drug dis­cov­ery and de­vel­op­ment, a biotech op­er­at­ing at the “nexus” of tech­nol­o­gy and neu­ro­sciences has cashed in with $76 mil­lion in fresh fi­nanc­ing.

The big idea at Black­Thorn Ther­a­peu­tics is to do for neu­robe­hav­ioral dis­or­ders what ge­net­i­cal­ly tar­get­ed ther­a­py has done for on­col­o­gy: Re­de­fine pa­tient pop­u­la­tions by the un­der­ly­ing bi­ol­o­gy — dys­reg­u­lat­ed brain cir­cuits, or neu­rotypes — in­stead of symp­toms, there­by find­ing the pa­tients who are most like­ly to ben­e­fit at en­roll­ment phase.