Fresh safe­ty, tol­er­a­bil­i­ty da­ta snap­shot from ear­ly-stage study of Wave's DMD drug spooks in­vestors

Wave Life Sci­ences irked in­vestors with the lat­est snap­shot of safe­ty da­ta on its ex­per­i­men­tal Duchenne mus­cu­lar dy­s­tro­phy (DMD) drug on Tues­day, caus­ing Wall Street to ques­tion whether the re­sults from the ear­ly-stage study fore­shad­owed trou­ble ahead.

The ex­per­i­men­tal drug, su­vodirsen, is be­ing test­ed in the same DMD pop­u­la­tion that Sarep­ta’s $SRPT pi­o­neer­ing Ex­ondys 51 is ap­proved to treat — boys who are amenable to ex­on 51 skip­ping. In the Phase I study, 36 pa­tients re­ceived a dose of 0.5 mg/kg, 1 mg/kg, 2 mg/kg, 5 mg/kg, 7 mg/kg or 10 mg/kg of su­vodirsen (n=26) or place­bo (n=10) in five as­cend­ing dose co­horts and were fol­lowed for 85 days.

Re­sults from the first four co­horts (0.5 mg/kg – 5 mg/kg) showed that 16/24 pa­tients who re­ceived su­vodirsen and 8/10 pa­tients who re­ceived the place­bo ex­pe­ri­enced one or more ad­verse events of mild-to-mod­er­ate in­ten­si­ty in­clud­ing pyrex­ia, headache, vom­it­ing and tachy­car­dia.

On Tues­day, da­ta from the fifth co­hort — 2 pa­tients ad­min­is­tered with the 7 mg/kg or 10 mg/kg dose of su­vodirsen — were un­veiled. Sim­i­lar side ef­fects were re­port­ed as those ob­served at low­er dos­es, but were more se­vere in in­ten­si­ty, Wave said. The Cam­bridge, Mass­a­chu­setts-based com­pa­ny’s shares $WVE tum­bled more than 28% to close up at $24.47 on Tues­day, as in­vestors took is­sue with the drug’s tol­er­a­bil­i­ty pro­file.

Paul Mat­teis

These “ap­pear to be dose-lim­it­ing im­muno­tox­i­c­i­ties…it’s un­clear if this pro­file will get bet­ter or worse up­on re­peat dos­ing,” Stifel’s Paul Mat­teis wrote in a note.

For the piv­otal Phase II/III tri­al — ex­pect­ed to com­mence in Ju­ly 2019 — Wave has cho­sen to eval­u­ate 3.0 or 4.5 mg/kg of su­vodirsen once week­ly for 48 weeks in 150 boys. How­ev­er, an im­prove­ment in man­u­fac­tur­ing has al­lowed the com­pa­ny to arm the 4.5 mg/kg dose with the same quan­ti­ty of ac­tive in­gre­di­ent as the 5 mg/kg used in the Phase I study.

“The fact that FDA has signed off on this tri­al is a pos­i­tive, but it’s hard for us to have con­vic­tion that these dose lev­els will be suf­fi­cient,” Mat­teis added.

An­oth­er pos­si­ble stick­ing point is the com­par­i­son of su­vodirsen with Bio­Marin’s $BM­RN re­ject­ed DMD drug, dris­apersen, SVB Leerink’s Mani Foroohar wrote in a note.

Mani Foroohar

“(I)nvestors seem to see neg­a­tive read-throughs for the po­ten­tial ef­fi­ca­cy of su­vodirsen at 5 mg/kg, giv­en that dris­apersen was dosed at 6 mg/kg in clin­i­cal tri­als, we be­lieve that due to dif­fer­ences in chem­istry be­tween the com­pounds, com­par­i­son of dos­es be­tween drugs is not an ap­pro­pri­ate proxy of po­ten­tial ef­fi­ca­cy.”

Foroohar said he was main­tain­ing a 30% prob­a­bil­i­ty of suc­cess on the su­vodirsen pro­gram.

“We be­lieve we have se­lect­ed the op­ti­mal dos­es to bring for­ward in our on­go­ing open-la­bel ex­ten­sion study and planned Phase 2/3 tri­al. We look for­ward to shar­ing the dy­s­trophin re­sults from mus­cle biop­sies tak­en from the open-la­bel ex­ten­sion study in the sec­ond half of this year,” Wave chief Paul Bol­no said in an emailed state­ment.

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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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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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).

Bain’s biotech team has cre­at­ed a $1B-plus fund — with an eye to more Big Phar­ma spin­outs

One of the biggest investors to burst onto the biotech scene in recent years has re-upped with more than a billion dollars flowing into its second fund. And this next wave of bets will likely include more of the Big Pharma spinouts that highlighted their first 3 years in action.

Adam Koppel and Jeff Schwartz got the new life sciences fund at Bain Capital into gear in the spring of 2016, as they were putting together a $720 million fund with $600 million flowing in from external investors and the rest drawn from the Bain side of the equation. This time the external investors chipped in $900 million, with Bain coming in for roughly $180 million more.

They’re not done with Fund I, with plans to add a couple more deals to the 15 they’ve already posted. And once again, they’re estimating another 15 to 20 investments over a 3- to 5-year time horizon for Fund II.

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