Dy­navax takes a big step to­ward an OK for hep B vac­cine, but nag­ging safe­ty is­sues re­main

Ed­die Gray, Dy­navax CEO

Will the third time prove the charm for Dy­navax?

More than a few an­a­lysts are still ask­ing that ques­tion af­ter a pan­el of out­side ex­perts formed by the FDA of­fered a lop­sided vote in fa­vor of an ap­proval — with three ab­sten­tions for its hep B vac­cine Hep­lisav and on­ly one op­posed for safe­ty rea­sons.

Ef­fi­ca­cy was nev­er re­al­ly in doubt. The da­ta are sol­id. But there was plen­ty of fret­ting about Hep­lisav’s safe­ty pro­file, af­ter reg­u­la­tors spot­light­ed an im­bal­ance of deaths and car­diac events which has nev­er been ex­plained. The in­ter­nal FDA re­view last Wednes­day forced the stock $DVAX down 10%, but it rock­et­ed up 80% Fri­day evening af­ter the ex­perts weighed in on ways that the biotech could keep a care­ful eye on the health of the peo­ple tak­ing their vac­cine.

Whether the FDA signs off on that and green-lights the vac­cine, af­ter post­ing a sol­id set of da­ta in com­par­i­son with Glax­o­SmithK­line’s En­ger­ix-B, is now the big ques­tion. The agency on­ly rarely bucks its out­side ex­perts, and the man­date at the agency now is def­i­nite­ly in fa­vor of ap­provals over de­lay.

This pro­gram has al­ready been stiff-armed twice at the FDA, fol­low­ing a clin­i­cal hold ear­ly on in 2008.

RBC’s Matt Eck­ler is bet­ting that the com­pa­ny and the FDA can square away a plan for phar­ma­covig­i­lance, al­low­ing an ap­proval by Au­gust 10 and a launch next year — whether or not the biotech can land a part­ner. But there are plen­ty of un­re­solved ques­tions re­gard­ing the de­tails and how they may in­flu­ence the com­mer­cial re­cep­tion. He wrote:

Pri­or to the pos­i­tive vote, pan­el mem­bers ex­pressed lin­ger­ing con­cerns over the MI (my­ocar­dial in­farc­tion) sig­nal seen in HBV-23, as well as the suf­fi­cien­cy of the pro­posed de­sign of the post mar­ket­ing sur­veil­lance pro­gram. The cur­rent pro­pos­al from DVAX is to con­duct ob­ser­va­tion­al elec­tron­ic med­ical record re­view at Kaiser Per­ma­nente North­ern Cal­i­for­nia to com­pare 3-point MACE, and pre-spec­i­fied im­mune-me­di­at­ed events, in 20,000 Hep­lisav-B re­cip­i­ents vs 20,000 per­sons who re­ceive an­oth­er he­pati­tis B vac­cine. Based on this de­sign, the first in­ter­im analy­sis is es­ti­mat­ed with­in 12 months fol­low­ing ini­ti­a­tion. No­table pan­el mem­ber con­cerns with the de­sign in­clud­ed the po­ten­tial for se­lec­tion against high-risk pa­tients, which would lim­it the abil­i­ty to de­tect a safe­ty sig­nal, as well as the ca­pac­i­ty to pro­vide de­fin­i­tive an­swers with­in a rea­son­able time frame. Ad­di­tion­al­ly, pan­el mem­bers ex­pressed the view that full safe­ty da­ta should be in Hep­lisav’s la­bel, but that such a la­bel may cause physi­cians to se­lect against us­ing in high-risk pa­tients for whom the un­met med­ical need is great­est.

Dy­navax is bet­ting that the eas­i­er dos­ing reg­i­men will give them an edge in the mar­ket over the GSK ri­val, but there are no sure things in this mar­ket.

“The two-dose reg­i­men of­fers the po­ten­tial to in­crease pa­tient com­pli­ance, which physi­cians and ad­vo­cates agree is es­sen­tial to pre­vent­ing more cas­es of he­pati­tis B and achiev­ing the pub­lic health goal of erad­i­ca­tion,” said CEO Ed­die Gray in a state­ment. “We look for­ward to com­plet­ing our on­go­ing dis­cus­sions with the FDA re­gard­ing an ap­pro­pri­ate post-mar­ket­ing com­mit­ment as it fi­nal­izes its re­view.”

We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology

ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development

CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at help@endpointsnews.com with any issues.

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Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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UP­DAT­ED: Pay­back? An­a­lysts say Sarep­ta was blind­sided by an FDA re­jec­tion dri­ven by reg­u­la­to­ry re­venge

In one of the least anticipated moves of the year, the FDA has rejected Sarepta’s application for an accelerated approval of its Duchenne MD drug golodirsen after fretting over safety issues.

In a statement that arrived after the bell on Monday, Sarepta explained the CRL, saying:

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FDA de­ci­sion on Ver­tex's CF triple will come just ahead of planned CEO shake­up

Vertex has clinched a priority review for the all-important cystic fibrosis triple that will blaze the trail for treating a large group of patients unhelped by its current drugs.

FDA regulators have set a PDUFA date of March 19, 2020, just a year after the Boston biotech posted positive Phase III results showing that people with two F508del mutations experienced statistically significant improvements in lung function after a 4-week regimen of VX-445, tezacaftor and ivacaftor. After reviewing 24-week data among patients with one F508del mutation and one minimal function mutation — and thoroughly comparing the VX-445 triple with another combo featuring VX-659 on scores like safety, drug-drug interactions, and photosensitivity — Vertex ultimately went with VX-445.

An MIT spin­out kills one of its ‘liv­ing ther­a­peu­tics’ af­ter flunk­ing an ear­ly-stage study — shares rout­ed

Just a few weeks after bagging $80 million in a deal to collaborate with Gingko Bioworks on its special blend of engineered bacteria used for “living therapeutics,” little Synlogic in Boston $SYBX is tossing one of its two clinical programs after watching an early-stage study go down in defeat.

Their Phase Ib/IIa study for SYNB1020 to counter the accumulation of ammonia in the body, a condition called hyperammonemia or urea cycle disorder, floundered at the interim readout, forcing the biotech to kill it and reserve its cash for pipeline therapies with greater potential.

Elan­co to buy Bay­er's an­i­mal health busi­ness for $7.6B, as deal­mak­ing gath­ers steam in the sec­tor

Last week, Elanco explicitly dodged answering questions about its rumored interest in Bayer’s animal health business in its post-earnings call. On Tuesday, the Eli Lilly spinoff disclosed it was purchasing the German drug maker’s veterinary unit in a cash-and-stock deal worth $7.6 billion. 

Elanco $ELAN has been busy on the deal-making front. In April, it laid out plans to swallow its partner, Kansas-based pet therapeutics company Aratana $PETX. A July report by Reuters suggested a potential Bayer deal was being explored, and Bloomberg last week said the deal was imminent, citing sources. 

As­traZeneca's di­a­betes drug Farx­i­ga helps pa­tients with heart dis­ease and with­out di­a­betes in land­mark tri­al

Months ago, data on J&J’s $JNJ Invokana indicated the diabetes drug conferred cardiovascular (CV) benefit in patients who do and do not have preexisting CV disease. On Tuesday, AstraZeneca’s $AZN rival treatment, Farxiga, was shown to cut the risk of CV death or the worsening of heart failure in patients with heart disease, in a landmark trial.

The treatments, in addition to Jardiance from Eli Lilly $LLY, belong to a class of diabetes drugs called sodium-glucose co-transporter 2 (SGLT2) inhibitors, which work by curbing the absorption of glucose via the kidneys so that surplus glucose is excreted through urination.

Levi Garraway. Broad Institute via Youtube

Roche raids Eli Lil­ly for its next chief med­ical of­fi­cer as San­dra Horn­ing plans to step down

We found out Monday morning where Levi Garraway was headed after he left Eli Lilly as head of oncology R&D a few days ago. Roche named Garraway as their new chief medical officer, replacing Sandra Horning, who they say is retiring from the company.

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Af­ter a posse of Wall Street an­a­lysts pre­dict a like­ly new win for Sarep­ta, we're down to the wire on a crit­i­cal FDA de­ci­sion

As Bloomberg notes, most of the Wall Street analysts that cover Sarepta $SRPT are an upbeat bunch, ready to cheer on the team when it comes to their Duchenne MD drugs, or offer explanations when an odd setback occurs — as happened recently with a safety signal that was ‘erroneously’ reported last week.

Ritu Baral Cowen
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