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.”

Albert Bourla appears before the Senate Committee on Finance for a hearing on prescription drug pricing on Capitol Hill in Washington, DC, February 26, 2019. Chris Kleponis for CNP via AP Images

UP­DAT­ED: Pfiz­er CEO Al­bert Bourla is back in the M&A game, but why is he pay­ing $11.4B for Ar­ray?

Pfiz­er $PFE has cut short its time on the side­lines of bio­phar­ma M&A.

Mon­day morn­ing the phar­ma gi­ant un­veiled an $11.4 bil­lion deal to ac­quire Ar­ray Bio­Phar­ma, beef­ing up its on­col­o­gy work and adding a new re­search hub in Boul­der, Col­orado to its glob­al op­er­a­tions.

At $48 a share, Ar­ray $AR­RY in­vestors will be get­ting a 62% pre­mi­um off the Fri­day close of $29.59.

Pfiz­er, which has strug­gled to gain all the up­side promised in past buy­outs like Medi­va­tion, high­light­ed the ac­qui­si­tion of 2 ap­proved drugs in the deal — Braftovi (en­co­rafenib) and Mek­tovi (binime­tinib).

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In­vestors fret as VBI's hep B vac­cine fails key sec­ondary PhI­II study goal

Sobered by mount­ing costs, Dy­navax $DVAX last month made the de­ci­sion to fo­cus all its re­sources on its 2017-ap­proved he­pati­tis B vac­cine Hep­lisav-B, which ri­vals and su­per­sedes the ef­fi­ca­cy and con­ve­nience pro­file of GSK’s $GSK es­tab­lished En­ger­ix-B. The Cal­i­for­nia-based com­pa­ny will be on the look­out for an­oth­er com­peti­tor — VBI Vac­cines, which on Mon­day un­veiled late-stage da­ta on its hep B vac­cine: Sci-B-Vac.

Image: Shutterstock

Gene ther­a­py R&D deals turn red hot as Big Phar­ma steps up to play

This September will mark the 20th anniversary of the death of Jesse Gelsinger, a young man suffering from X-linked genetic disease of the liver. He was killed in a gene therapy study conducted by Penn’s James Wilson, and the entire field endured a lengthy deep freeze as the field grappled with the safety issues inherent in the work.

Some thought gene therapy R&D would never survive. But it did. And this year marked a landmark approval for Zolgensma, a new gene therapy for spinal muscular atrophy Novartis priced at $2.1 million.

“Gene therapy is the hottest item on the block now. But there was a time when we first got into this trial, where there wasn’t a person in the world who believed that gene therapy would work. We have to remember that,” noted gene therapy investigator Jerry Mendell told SMA News Today.

We’re still right on the pioneering frontier when it comes to getting approvals for gene therapies and launching marketing campaigns with the European green light for bluebird's leading program last Friday underscoring the nascent nature of the field. But gene therapy R&D is booming, and has been for several years now.

The rapid growth of gene therapy clinical development is well known, but we decided to put some numbers on it, to quantify what’s going on. DealForma chief Chris Dokomajilar took a lot over the past 10 years, as the number of deals, R&D partnerships and buyouts steadily gained steam, spiking last year and on track to maintain the surge in 2019.

The upfronts and totals for the dollars on deals so far in 2019 is already close to the 2018 mark, underscoring a new phase of negotiations as the major players step up to gain a piece of the late-stage and commercial action.

Once again, we’re looking at an “overnight” biotech success story, decades in the making.

At some point, that may start to brake the numbers we’re seeing. But for now, as rivals line up to compete for frontline prominence across a range of diseases, the arrows are all pointed north.

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A uni­corn stalks Wall Street in search of IPO cash; CASI Phar­ma in-li­cens­es CD19 ther­a­py from Chi­na’s Ju­ven­tas

→ A herd of up­start biotechs will look to Wall Street for some ma­jor wind­falls this week as a burst of new of­fer­ings con­tin­ues to feed cash in­to the R&D sys­tem. To­day we learned that Bridge­Bio will look to raise in the neigh­bor­hood of $225 mil­lion by of­fer­ing 15 mil­lion shares for $14 to $16 each. And they have a string of joint bookrun­ners: J.P. Mor­gan, Gold­man Sachs, Jef­feries, SVB Leerink, KKR, Piper Jaf­fray, Mizuho Se­cu­ri­ties, BMO Cap­i­tal Mar­kets and Ray­mond James. If suc­cess­ful, Bridge­Bio will emerge with a mar­ket cap of around $1.7 bil­lion. There are 5 biotechs look­ing to IPO this week, in­clud­ing Akero and Pre­vail.

UP­DAT­ED: Sanofi Gen­zyme deserts gene ther­a­py de­vel­op­er Voy­ager Ther­a­peu­tics

While gene ther­a­py com­pa­nies re­joice as the sec­tor gains trac­tion with ap­provals and a flur­ry of M&A ac­tiv­i­ty, one play­er is feel­ing the heat.

Back in 2015, Voy­ager Ther­a­peu­tics joined forces with Sanofi Gen­zyme in a deal worth up to $845 mil­lion ($100 mil­lion up­front + a po­ten­tial $745 mil­lion in mile­stones) to co-de­vel­op gene ther­a­pies for se­vere cen­tral ner­vous sys­tem dis­or­ders. But two years lat­er, the French drug­mak­er re­treat­ed, elect­ing to not pick up the op­tion to work on Voy­ager’s Parkin­son’s dis­ease pro­gram. (Last year, the FDA dis­ap­point­ed Voy­ager, telling the com­pa­ny that it was not open to an ac­cel­er­at­ed fil­ing on the Parkin­son’s drug on the ba­sis of Phase II da­ta — in­stead of re­quir­ing an ad­di­tion­al piv­otal study.)

John Oyler, Founder & CEO of BeiGene, at the US-China Biopharma Innovation and Investment Summit in Shanghai on October 23, 2018; Credit: Endpoints News, PharmCube

UP­DAT­ED: As Bris­tol-My­ers/Cel­gene tie up loose ends, BeiGene pock­ets $150M from PD-1 breakup

As soon as Bristol-Myers Squibb announced its $74 billion buyout for Celgene, BeiGene emerged as a prominent example of a player whose pact with the big biotech could sour, as its PD-1 candidate seems to overlap with Opdivo. After six months of suspense, the partners say they are finally bringing the 2-year-old deal to an amicable end.

BeiGene $BGNE gets $150 million for the termination in addition to full global rights to tislelizumab. In 2017 Celgene had paid $263 million in upfront license fees to develop the PD-1 inhibitor for solid cancers in the US, Europe, Japan and the rest of the world outside Asia. It also threw in a $150 million equity investment in exchange for BeiGene handling its commercial operations — think Abraxane, Revlimid and Vidaza — in China.

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Exterior of the 1 million square foot Discovery Labs in Upper Merion, PA (PR Newswire)

Philadel­phia cham­pi­ons life sci­ences 'co-work­ing,' re­viv­ing for­mer GSK cam­pus in $500M makeover

In a boost to Philadel­phia’s thriv­ing life sci­ences scene, a for­mer Glax­o­SmithK­line cam­pus and a near­by site has been turned in­to what its de­vel­op­er calls “the largest cowork­ing ecosys­tem” for health­care com­pa­nies in the coun­try.

The Dis­cov­ery Labs, a com­pa­ny spawned by MLP Ven­tures, has se­lect­ed two lo­ca­tions in the King of Prus­sia area as the $500 mil­lion test case for its strat­e­gy of ac­quir­ing and con­vert­ing old phar­ma­ceu­ti­cal R&D fa­cil­i­ties world­wide. The sites add up to 1.64 mil­lion square feet.

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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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.