Ver­tex's new dilem­ma: With more pos­i­tive PhI­II da­ta on hand, which of their promis­ing com­bos should go to the FDA, EMA?

Ver­tex $VRTX has a pleas­ant dilem­ma on its hands.

The big biotech re­port­ed that its Phase III tri­al for a cock­tail used to treat cys­tic fi­bro­sis has come in with pos­i­tive re­sults for VX-445, teza­caftor and iva­caftor.

In fact, they’re al­most iden­ti­cal to the Phase III re­sults they got for VX-659 com­bined with teza­caftor and iva­caftor. And that means the ju­ry on which triple will head to reg­u­la­tors on both sides of the At­lantic is still out.

Now the ex­ec­u­tives at Ver­tex say they’ll wait for 24-week da­ta due on both late-stage com­bi­na­tions in Q2, then de­cide which will get pitched to the FDA and EMA. Bot­tom line:

Da­ta from a pre-spec­i­fied in­ter­im analy­sis of the Phase III study in peo­ple with one F508del mu­ta­tion and one min­i­mal func­tion mu­ta­tion showed a mean ab­solute im­prove­ment in ppFEV1 of 13.8 per­cent­age points from base­line at week 4 of treat­ment com­pared to place­bo (p<0.0001). In the Phase 3 study in peo­ple with two F508del mu­ta­tions, the ad­di­tion of VX-445 in pa­tients al­ready re­ceiv­ing teza­caftor and iva­caftor re­sult­ed in a mean ab­solute im­prove­ment in ppFEV1 of 10.0 per­cent­age points from base­line at week 4 of treat­ment com­pared to the con­trol group in whom place­bo was added to teza­caftor and iva­caftor (p<0.0001).

VX-659 was cred­it­ed with a 14% place­bo-ad­just­ed im­prove­ment from base­line in FEV1 for pa­tients with one F508del mu­ta­tion and one min­i­mal func­tion mu­ta­tion, with a clear score on the p val­ue (p<0.0001). In a sep­a­rate Phase III pa­tients ho­mozy­gous for the F508del mu­ta­tion al­ready tak­ing Symdeko saw an av­er­age 10% im­prove­ment with VX-659 added on.

Cue the en­thu­si­as­tic re­sponse from an­a­lysts. Not­ed SVB Leerink’s Ge­of­frey Porges:

This triple da­ta is, if any­thing, even bet­ter than the pre­vi­ous­ly re­leased VX-659 triple re­sults, and in our view ef­fec­tive­ly guar­an­tees the launch, ap­proval, com­mer­cial­iza­tion and adop­tion of one of these com­bi­na­tions, with re­sult­ing mul­ti-bil­lion dol­lar sales to Ver­tex (re­gard­less of the UK’s in­tran­si­gence). ​

Resh­ma Ke­wal­ra­mani

“Both the VX-659 and VX-445 triple com­bi­na­tion reg­i­mens showed high­ly con­sis­tent and sig­nif­i­cant im­prove­ments in lung func­tion across our Phase III pro­grams, un­der­scor­ing the im­por­tant clin­i­cal ben­e­fit that a triple com­bi­na­tion reg­i­men may pro­vide to pa­tients with two F508del mu­ta­tions and to those with one F508del and one min­i­mal func­tion mu­ta­tion,” said Ver­tex CMO Resh­ma Ke­wal­ra­mani. “We look for­ward to sub­mit­ting glob­al reg­u­la­to­ry ap­pli­ca­tions for one of these triple com­bi­na­tion reg­i­mens for both pa­tient pop­u­la­tions lat­er this year.”

Ver­tex has ac­quired quite a cheer­ing sec­tion among an­a­lysts cov­er­ing the mar­ket, with many see­ing the com­pa­ny step­ping up with a triple that can sig­nif­i­cant­ly broad­en their mar­ket share.

Once ap­proved — if the op­ti­mists are cor­rect — Ver­tex will al­so throw their com­bo in­to the bat­tle over ac­cess in Eu­rope. Sev­er­al sin­gle pay­er sys­tems, most no­tably the UK, have bucked at the price of their best­seller Orkam­bi. But CEO Jeff Lei­den has waged a PR war against his pric­ing foes, adamant­ly seek­ing more than what NICE and oth­ers are will­ing to pay. 

That show­down will come to a head to­mor­row, as Ver­tex ex­ecs square off with pub­lic health of­fi­cials in a high pro­file, head-to-head bat­tle over the price. The triple can on­ly add more heat to the al­ready fetid con­fronta­tion that has now lin­gered for 3 years, with pa­tients caught in the mid­dle.

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.

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).