New Zol­gens­ma da­ta sug­gest com­pa­ra­ble ef­fi­ca­cy to Spin­raza — an­a­lysts

As No­var­tis awaits the FDA de­ci­sion on its spinal mus­cu­lar at­ro­phy (SMA) gene-ther­a­py, Zol­gens­ma, the com­pa­ny that de­vel­oped the treat­ment for the rare, dead­ly in­her­it­ed dis­or­der, AveX­is, pre­sent­ed da­ta snap­shots from on­go­ing tri­als on Sun­day, prompt­ing an­a­lysts to sug­gest that the one-shot ther­a­py was look­ing com­pa­ra­ble to Bio­gen’s ap­proved Spin­raza.

In the on­go­ing late-stage STR1VE study, de­signed to eval­u­ate the ef­fi­ca­cy and safe­ty of a one-time IV in­fu­sion of Zol­gens­ma in pa­tients with SMA Type 1 who are <6 months of age, da­ta showed pa­tients con­tin­ued to show event-free sur­vival well above nor­mal his­tor­i­cal con­trols, AveX­is sug­gest­ed at the Amer­i­can Acad­e­my of Neu­rol­o­gy an­nu­al meet­ing.

SMA caus­es mus­cle weak­ness and pro­gres­sive loss of move­ment, trig­gered by a ge­net­ic de­te­ri­o­ra­tion in the nerve cells con­nect­ing the brain and spinal cord to the body’s mus­cles. Ba­bies with type 1 rarely sur­vive be­yond the first few years of life, while most chil­dren with type 2 sur­vive in­to adult­hood. Types 3 and 4 don’t usu­al­ly af­fect life ex­pectan­cy. The Swiss drug­mak­er has sug­gest­ed a price of $4 -$5 mil­lion for Zol­gens­ma, which it ac­quired via its $8.7 bil­lion takeover of AveX­is.

An­oth­er sig­nif­i­cant up­date was the snap­shot from the STRONG study, which is eval­u­at­ing the in­trathe­cal de­liv­ery of Zol­gens­ma in pa­tients with SMA Type 2. Pa­tients were strat­i­fied in­to two groups based on age at time of dos­ing: pa­tients who are ≥6 months but <24 months, and pa­tients who are ≥24 months but <60 months. The pri­ma­ry ef­fi­ca­cy out­come for pa­tients in the first group is the abil­i­ty to stand with­out sup­port ≥3 sec­onds; the main goal for the sec­ond group is a change in Ham­mer­smith Func­tion­al Mo­tor Scale-Ex­pand­ed (HFMSE) score from base­line. Since dos­ing, 22 mo­tor mile­stones in 10 pa­tients have been achieved across Dose A and Dose B, in­clud­ing two pa­tients who gained the abil­i­ty to stand in­de­pen­dent­ly, one of whom went on to walk alone, and one pa­tient who gained the abil­i­ty to walk with as­sis­tance. The me­di­an du­ra­tion of fol­low-up was 6.5 months and all 30 pa­tients are alive.

“The av­er­age age at en­roll­ment in STRONG was 17 months…these re­sults are chal­leng­ing to in­ter­pret or com­pare with the Spin­raza da­ta since the Bio­gen/Io­n­is study en­rolled pa­tients who were slight­ly old­er (3 years at base­line). Thus, we be­lieve the most com­pa­ra­ble dat­a­point is ef­fi­ca­cy on the HFMSE, which was the pri­ma­ry end­point in Bio­gen/Io­n­is’ Spin­raza tri­al. On this mea­sure, AVXS-101 pro­duced a mean 4.2 point im­prove­ment at a me­di­an fol­low up time of 7.5 months; by com­par­i­son, Spin­raza gen­er­at­ed a ~3 point im­prove­ment at 9 months in the Phase III CHER­ISH study. The mag­ni­tude of these im­prove­ments are ob­vi­ous­ly very close to one an­oth­er, and when we think about STRONG/CHER­ISH de­signs and the re­cruit­ed tri­al pop­u­la­tions, the bal­ance of con­found­ing vari­ables prob­a­bly fa­vors the STRONG study a lit­tle, un­der­ly­ing our con­clu­sion that the ef­fi­ca­cy of gene ther­a­py and Spin­raza are prob­a­bly pret­ty sim­i­lar,” Stifel an­a­lysts wrote in a note.

Ever­core ISI’s Umer Raf­fat sug­gest­ed that in the sec­ond group, al­though Zol­gens­ma ap­pears to kick in faster, both the gene-ther­a­py and Bio­gen’s $BI­IB Spin­raza plateau at the same. But, there is one cru­cial caveat — the pa­tients in AveX­is tri­al seemed to have low­er HFMSE scores to be­gin with, he wrote.

Over­all, no treat­ment-emer­gent deaths have been pre­sent­ed in the new da­ta, he not­ed. Rough­ly two weeks ago, AveX­is dis­closed that one of the in­fants in the STR1VE-EU study died from an in­fec­tion, and au­thor­i­ties are in­ves­ti­gat­ing whether Zol­gens­ma played a role in the death. Al­though reg­u­la­to­ry bod­ies are ex­pect­ed to be ac­com­mo­dat­ing for safe­ty is­sues when it comes to a po­ten­tial once-and-done treat­ment for the lethal dis­ease, com­pe­ti­tion ab­sent these safe­ty con­cerns could cer­tain­ly tem­per adop­tion.

The AveX­is da­ta “looks com­pet­i­tive and like a vi­able op­tion for pa­tients, in­clud­ing new in­trathe­cal dos­ing for Type 2, etc, and be­yond just in­fants (where gene ther­a­py is most com­pet­i­tive to start). We think FDA ap­proval and a fair­ly ‘broad la­bel’ could be com­ing for No­var­tis as soon as this week. Our doc sur­vey sug­gests more than 1/3 of pa­tients could opt for this; hence, Bio­gen es­ti­mates may be too high for Spin­raza,” Jef­feries an­a­lysts wrote in a note.

PTC Ther­a­peu­tics $PTCT and Roche’s oral SMA ther­a­py, ris­diplam, will like­ly be tak­en to the FDA for re­view  lat­er this year for a broad pop­u­la­tion, and could be on the mar­ket by the end of 2020, they added.

“Bot­tom line — we could see a 1/3, 1/3, 1/3 split of mar­ket over time,” Jef­feries an­a­lysts said. Doc­tors sug­gest gene ther­a­pies “could be 30-33% share of new SMA Type I-III pa­tients over time. An es­ti­mat­ed 20-25% could look to switch from Spin­raza to gene ther­a­py (de­pends on weight of pa­tient). 2) Sim­i­lar­ly, docs sug­gest 1/3 share for oral ris­diplam, too, af­ter 3-5 years; 3) Com­men­tary by docs sug­gests an even split of opin­ions on the mar­ket as well — from oral pills ‘very ap­peal­ing’ and ‘game chang­er’ and ‘es­pe­cial­ly at­trac­tive for teens/adults’ to oth­er ther­a­pies need more da­ta and like­ly com­bo,” cit­ing their sur­vey.

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.

Ted Love. HAVERFORD COLLEGE

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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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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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.

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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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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Fol­low­ing CAR-T pi­o­neer­s' foot­steps, Tes­sa launch­es Chi­na JV in $120M deal

These days just about every biotech se­ri­ous about glob­al de­vel­op­ment — and not just com­mer­cial­iza­tion — has a Chi­na strat­e­gy. Tes­sa Ther­a­peu­tics, a Bay­lor as­so­ci­at­ed out­fit based out of Sin­ga­pore, is no ex­cep­tion.

Tak­ing a page out of the CAR-T pi­o­neers’ play­book, Tes­sa is es­tab­lish­ing a joint ven­ture with Chi­na-Sin­ga­pore Guangzhou Knowl­edge City, which is ini­tial­ly putting down $40 mil­lion for a 13% stake with $40 mil­lion more to come in a sec­ond stage. The biotech, which now re­tains an 87% con­trol, is al­so rolling out its own con­tri­bu­tions in two phas­es, start­ing with $20 mil­lion and all its tech­nol­o­gy li­cense rights for Chi­na.

Cue the M&A chat­ter: UniQure is scout­ing for a buy­out deal as gene ther­a­py field siz­zles — re­port

All the en­thu­si­asm that’s been whipped up in the gene ther­a­py field this past year has helped stoke the ru­mor mill about all sorts of pos­si­bil­i­ties for uniQure $QURE, which has seen a quick run-up on its share price. And now the biotech’s back­ers are get­ting a big boost from Bloomberg to keep the run go­ing.

There’s no deal to re­port, but sources are telling the busi­ness news ser­vice that uniQure has brought in ad­vis­ers to see what might be done — in­clud­ing a sale — with the phar­ma gi­ants now prowl­ing the clin­i­cal play­ers for part­ners and ac­qui­si­tions.