Bone mar­row trans­plant sparks long-term re­mis­sion in sec­ond HIV pa­tient, re­new­ing hope for a cure

The cau­tious­ly op­ti­mistic call it sus­tained re­mis­sion, oth­ers are hope­ful it is a cure — but the doc­tors are im­pressed. An un­named pa­tient in Lon­don, once af­flict­ed with can­cer and the virus that caus­es AIDS, is free of both, cour­tesy an im­mune sys­tem over­haul trig­gered by a bone mar­row trans­plant from an HIV-re­sis­tant donor.

The case comes a dozen years or so af­ter the “Berlin pa­tient” — now iden­ti­fied as Tim­o­thy Ray Brown — who achieved sus­tained re­mis­sion fol­low­ing the same pro­ce­dure for his leukemia. Al­though Brown un­der­went two trans­plants, was giv­en to­tal body ir­ra­di­a­tion no longer in use to­day, and was placed in an in­duced co­ma, he even­tu­al­ly re­cov­ered and was deemed HIV-free. Sci­en­tists took note, and tried re­peat­ed­ly to du­pli­cate the feat, but in vain.

Ravin­dra Gup­ta

On Tues­day re­searchers from Uni­ver­si­ty Col­lege Lon­don and Im­pe­r­i­al Col­lege Lon­don, to­geth­er with teams at the Uni­ver­si­ty of Cam­bridge and the Uni­ver­si­ty of Ox­ford, re­port­ed the sec­ond known case of sus­tained re­mis­sion — in an in­di­vid­ual who asked to re­tain his anonymi­ty and is ac­cord­ing­ly just re­ferred to as the “Lon­don pa­tient”.

Both Brown and the Lon­don pa­tient re­ceived do­na­tions from donors with two copies of the al­lele that pre­vents the ex­pres­sion of CCR5, a gene com­mon­ly used by HIV as a back door in­to a cell. The trait is nat­u­ral­ly com­mon in parts of North­ern Eu­rope and con­fers the abil­i­ty to re­sist an HIV in­fec­tion from the AIDS virus. It is this trait that rogue Chi­nese sci­en­tist Jiankui He at­tempt­ed to con­fer via gene edit­ing in his wide­ly con­demned CRISPR ex­per­i­ment ear­li­er this year that cul­mi­nat­ed in the birth of two ge­net­i­cal­ly mod­i­fied twin ba­by girls.

The Lon­don pa­tient was di­ag­nosed with an HIV in­fec­tion in 2003, and in 2012 he be­gan tak­ing an­ti­retro­vi­ral (ARV) ther­a­py. Lat­er that year, it was con­firmed he had ad­vanced Hodgkin’s Lym­phoma. On top of chemother­a­py, he un­der­went the stem cell trans­plant in 2016. The surgery was rel­a­tive­ly un­com­pli­cat­ed, but not with­out side ef­fects, in­clud­ing mild graft-ver­sus-host dis­ease.

Chemother­a­py can be used to thwart HIV as it snuffs out cells that are di­vid­ing – and the re­searchers sug­gest that re­plac­ing im­mune cells de­void of the CCR5 re­cep­tor ap­pears to be the cru­cial in­gre­di­ent pre­clud­ing HIV from mak­ing a come­back.

Ed­uar­do Olavar­ria

Fol­low­ing the trans­plant, for 16 months the Lon­don pa­tient was giv­en ARV ther­a­py, af­ter which his treat­ment was in­ter­rupt­ed to eval­u­ate whether he was tru­ly in HIV re­mis­sion. Reg­u­lar and sen­si­tive test­ing has con­firmed that the pa­tient has in­deed re­mained in re­mis­sion 18 months since ARV ther­a­py was ceased.

“We need to un­der­stand if we could knock out this re­cep­tor in peo­ple with HIV, which may be pos­si­ble with gene ther­a­py,” said lead au­thor of the study Ravin­dra Gup­ta, in a state­ment.

Gup­ta was at UCL when the study — to be pub­lished in the jour­nal Na­ture on Tues­day — was con­duct­ed; he has since moved to the Uni­ver­si­ty of Cam­bridge.

“While it is too ear­ly to say with cer­tain­ty that our pa­tient is now cured of HIV, and doc­tors will con­tin­ue to mon­i­tor his con­di­tion, the ap­par­ent suc­cess of haematopoi­et­ic stem cell trans­plan­ta­tion of­fers hope in the search for a long-await­ed cure for HIV/AIDS,” added Pro­fes­sor Ed­uar­do Olavar­ria from Im­pe­r­i­al Col­lege Lon­don.

Ac­cord­ing to the WHO, there are near­ly 37 mil­lion peo­ple glob­al­ly liv­ing with HIV — of which rough­ly 60% are on ARV, as of 2017. Once a death sen­tence, the virus that caus­es AIDS is typ­i­cal­ly sup­pressed us­ing ARV ther­a­py and is now up­grad­ed to the po­si­tion of a chron­ic dis­ease.

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.