Sci­en­tists hold out hope for re­gen­er­a­tive in­fu­sion via brain im­plant — de­spite fail­ing its first test in Parkin­son's

A re­gen­er­a­tive ap­proach to treat­ing Parkin­son’s dis­ease — fea­tur­ing an im­plant to pump a pro­tein di­rect­ly in­to pa­tients’ brains — floun­dered on its first clin­i­cal test, but that hasn’t stopped re­searchers in the UK from hold­ing out hope that it can even­tu­al­ly work by restor­ing dam­aged brain cells.

Cham­pi­oned by Parkin­son’s UK, the treat­ment works by boost­ing the lev­els of GDNF, or glial cell line de­rived neu­rotroph­ic fac­tor, a nat­u­ral­ly oc­cur­ring pro­tein thought to pro­tect cells and help them re­cov­er or re­grow. To re­ceive the pro­tein — which is too large to pen­e­trate the blood-brain bar­ri­er — pa­tients first have to un­der­go a ro­bot-as­sist­ed surgery to have four tubes placed in­to their brains, then get hooked to a ma­chine that in­fuse GDNF to pre­cise lo­ca­tions of the brain via a port on the side of the head.

Af­ter con­firm­ing safe­ty with six pa­tients, sci­en­tists re­cruit­ed 35 more pa­tients to see if in­fus­ing GDNF this way led to im­prove­ments in Parkin­son’s symp­toms, from mo­tor move­ments to dai­ly ac­tiv­i­ties.

The short an­swer is no: The “en­cour­ag­ing signs of im­prove­ments” among pa­tients in the drug arm did not con­sti­tute a sig­nif­i­cant dif­fer­ence from the place­bo group.

Alan Whone

But prin­ci­pal in­ves­ti­ga­tor Alan Whone was quick to of­fer po­ten­tial ex­pla­na­tions, name­ly the short dou­ble-blind tri­al time (nine months), the rel­a­tive­ly low dosage of GDNF, and the stage that pa­tients were al­ready at by the time they en­rolled.

His op­ti­mism is backed up by some ev­i­dence that GDNF had promis­ing ef­fects on brain cells al­ready rav­aged by the dis­ease — show­ing a 100% im­prove­ment in a key area of the brain af­fect­ed in the con­di­tion com­pared to place­bo, which didn’t in­duce any change.

“The spa­tial and rel­a­tive mag­ni­tude of the im­prove­ment in the brain scans is be­yond any­thing seen pre­vi­ous­ly in tri­als of sur­gi­cal­ly de­liv­ered growth-fac­tor treat­ments for Parkin­son’s,” Whone said in a state­ment. “This rep­re­sents some of the most com­pelling ev­i­dence yet that we may have a means to pos­si­bly reawak­en and re­store the dopamine brain cells that are grad­u­al­ly de­stroyed in Parkin­son’s.”

Fur­ther­more, a nine-month fol­low-up pe­ri­od dur­ing which the place­bo group al­so switched to GNDF saw all par­tic­i­pants demon­strat­ing “mod­er­ate to large im­prove­ment in symp­toms” com­pared to their own base­line scores, bol­ster­ing the hope that the ef­fects on symp­toms were just lag­ging be­hind im­prove­ment in brain cells.

Erich Mohr

All of this spells “ex­cit­ing signs of promise” for de­vice man­u­fac­tur­er Ren­ishaw as well as Med­Ge­n­e­sis, the biotech de­vel­op­ing GDNF and div­ing in­to an in­creas­ing­ly crowd­ed field with plen­ty of small­er play­ers tied up with big part­ners, tout­ing new tech­nolo­gies like pro­tein degra­da­tion to gene ther­a­py.

“We be­lieve this ex­per­i­men­tal Parkin­son’s Dis­ease Com­pos­ite Re­sponse (PD­CORE) may bet­ter cap­ture the full ef­fects of GDNF and we’re work­ing to get it sci­en­tif­i­cal­ly val­i­dat­ed so that it can be used in fu­ture tri­als,” CEO Erich Mohr said.

GDNF de­vice. Cred­it: Mint­Mo­tion for Pas­sion­ate Pro­duc­tions

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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.

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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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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Savara shares are crushed as PhI­II tri­al flunks pri­ma­ry, key sec­on­daries — but they can’t stop be­liev­ing

In­vestors are in no mood to hear biotechs tout the suc­cess of a “key” sec­ondary end­point when the piv­otal Phase III flunks the pri­ma­ry goal. Just ask Savara. 

The Texas biotech $SVRA went look­ing for a sil­ver lin­ing as com­pa­ny ex­ecs blunt­ly con­ced­ed that Mol­gradex, an in­haled for­mu­la­tion of re­com­bi­nant hu­man gran­u­lo­cyte-macrophage colony-stim­u­lat­ing fac­tor (GM-CSF), failed to spur sig­nif­i­cant­ly im­proved treat­ment out­comes for pa­tients with a rare res­pi­ra­to­ry dis­ease called au­toim­mune pul­monary alve­o­lar pro­teinosis, or aPAP.

As an­oth­er an­tibi­otics biotech sinks in­to a cri­sis, warn­ings of a sec­tor ‘col­lapse’

Another antibiotics company is scrambling to survive today, forcing the company’s founding CEO to exit in a reorganization that eliminates its research capabilities as the survivors look to improve on minuscule sales of their newly approved treatment. And the news — on top of an alarming series of failures — spurred at least one figure in the field to warn of a looming collapse of the antimicrobial resistance research field.

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'We kept at it': Jef­frey Blue­stone plots late-stage come­back af­ter teplizum­ab shown to de­lay type 1 di­a­betes

Late-stage da­ta pre­sent­ed at the Amer­i­can Di­a­betes As­so­ci­a­tion an­nu­al meet­ing in 2010 pushed Eli Lil­ly to put a crimp on teplizum­ab as the phar­ma gi­ant found it un­able to re­set the clock on new­ly di­ag­nosed type 1 di­a­betes. At the same con­fer­ence but in dif­fer­ent hands nine years lat­er, the drug is mak­ing a crit­i­cal come­back by scor­ing suc­cess in an­oth­er niche: de­lay­ing the on­set of the dis­ease.

In a Phase II tri­al with 76 high-risk in­di­vid­u­als — rel­a­tives of pa­tients with type 1 di­a­betes who have di­a­betes-re­lat­ed au­toan­ti­bod­ies in their bod­ies — teplizum­ab al­most dou­bled the me­di­an time of di­ag­no­sis com­pared to place­bo (48.4 months ver­sus 24.4 months). The haz­ard ra­tio for di­ag­no­sis was 0.41 (p=0.006).