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.”

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Pfiz­er's big block­buster Xel­janz flunks its post-mar­ket­ing safe­ty study, re­new­ing harsh ques­tions for JAK class

When the FDA approved Pfizer’s JAK inhibitor Xeljanz for rheumatoid arthritis in 2012, they slapped on a black box warning for a laundry list of adverse events and required the New York drugmaker to run a long-term safety study.

That study has since become a consistent headache for Pfizer and their blockbuster molecule. Last year, Pfizer dropped the entire high dose cohort after an independent monitoring board found more patients died in that group than in the low dose arm or a control arm of patients who received one of two TNF inhibitors, Enbrel or Humira.

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Covid-19 roundup: EU and As­traZeneca trade blows over slow­downs; Un­usu­al unions pop up to test an­ti­bod­ies, vac­cines

After coming under fire for manufacturing delays last week, AstraZeneca’s feud with the European Union has spilled into the open.

The bloc accused the pharma giant on Wednesday of pulling out of a meeting to discuss cuts to its vaccine supplies, the AP reported. AstraZeneca denied the reports, saying it still planned on attending the discussion.

Early Wednesday, an EU Commission spokeswoman said that “the representative of AstraZeneca had announced this morning, had informed us this morning that their participation is not confirmed, is not happening.” But an AstraZeneca spokesperson later called the reports “not accurate.”

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Adeno-associated virus-1 illustration; the use of AAVs resurrected the gene therapy field, but companies are now testing the limits of a 20-year-old technology (File photo, Shutterstock)

Af­ter 3 deaths rock the field, gene ther­a­py re­searchers con­tem­plate AAV's fu­ture

Nicole Paulk was scrolling through her phone in bed early one morning in June when an email from a colleague jolted her awake. It was an article: Two patients in an Audentes gene therapy trial had died, grinding the study to a halt.

Paulk, who runs a gene therapy lab at the University of California, San Francisco, had planned to spend the day listening to talks at the American Association for Cancer Research annual meeting, which was taking place that week. Instead, she skipped the conference, canceled every work call on her calendar and began phoning colleagues across academia and industry, trying to figure out what happened and why. All the while, a single name hung in the back of her head.

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Pascal Soriot, AP

As­traZeneca CEO Pas­cal So­ri­ot sev­ers an un­usu­al board con­nec­tion, steer­ing clear of con­flicts while re­tain­ing im­por­tant al­liances

CSL Behring chief Paul Perreault scored an unusual coup last summer when he added AstraZeneca CEO Pascal Soriot to the board, via Zoom. It’s rare, to say the least, to see a Big Pharma CEO take any board post in an industry where interests can simultaneously connect and collide on multiple levels of operations.

The tie set the stage for an important manufacturing connection. The Australian pharma giant agreed to supply the country with 10s of millions of AstraZeneca’s Covid-19 vaccine, once it passes regulatory muster.

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Jackie Fouse, Agios CEO

Agios scores its sec­ond pos­i­tive round of da­ta for its lead pipeline drug — but that won't an­swer the stub­born ques­tions that sur­round this pro­gram

Agios $AGIO bet the farm on its PKR activator drug mitapivat when it recently decided to sell off its pioneering cancer drug Tibsovo and go back to being a development-stage company — for what CEO Jackie Fouse hoped would be a short stretch before they got back into commercialization.

On Tuesday evening, the bellwether biotech flashed more positive topline data — this time from a small group of patients in a single-arm study. And the executive team plans to package this with its earlier positive results from a controlled study to make its case for a quick OK.

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George Yancopoulos (L) and Len Schleifer (Regeneron)

Re­gen­eron touts pos­i­tive pre­lim­i­nary im­pact of its Covid an­ti­body cock­tail, pre­vent­ing symp­to­matic in­fec­tions in high-risk group

Regeneron flipped its cards on an interim analysis of the data being collected for its Covid-19 antibody cocktail used as a safeguard against exposure to the virus. And the results are distinctly positive.

The big biotech reported Tuesday morning that their casirivimab and imdevimab combo prevented any symptomatic infections from occurring in a group of 186 people exposed to the virus through a family connection, while the placebo arm saw 8 of 223 people experience symptomatic infection. Symptomatic combined with asymptomatic infections occurred in 23 people among the 223 placebo patients compared to 10 of the 186 subjects in the cocktail arm.

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As­traZeneca scores new goal on the pipeline front, adding its first AI-gen­er­at­ed tar­get to the port­fo­lio

As more and more biopharmas develop artificial intelligence platforms, the drug discovery process is being reshaped to fit new goals on cutting down the prodigious amount of time, energy and money that go into a drug program. Now one of the most ambitious players in the drive to improve on ROI, AstraZeneca, is marking a milestone on that front by adding the first target generated by AI to its portfolio.

Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

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