Hit-and-miss PhI­I­Is leave Lund­beck and Ot­su­ka’s lat­est Alzheimer’s pro­gram in a pre­car­i­ous po­si­tion

Sev­en months af­ter Lund­beck and Ot­su­ka re­port­ed a Phase III flop for their Alzheimer’s drug idalopir­dine, the part­ners are back with a hit-and-miss score on eas­ing Alzheimer’s ag­i­ta­tion for their block­buster ther­a­py Rex­ul­ti (br­ex­pipra­zole).

Al­ready ap­proved for schiz­o­phre­nia and ma­jor de­pres­sion, the col­lab­o­ra­tors were look­ing for the first ap­proval of an an­tipsy­chot­ic specif­i­cal­ly for ag­i­ta­tion trig­gered by Alzheimer’s de­men­tia, a con­di­tion that af­flicts mil­lions of peo­ple in the US and mil­lions more world­wide. Ag­i­ta­tion can be ex­pressed in many ways, run­ning from wan­der­ing to ag­gres­sive be­hav­ior.

But in try­ing to gain pos­i­tive da­ta reg­u­la­tors want to see from two big late-stage stud­ies, re­searchers scored a hit on the pri­ma­ry — change from base­line in the Co­hen-Mans­field Ag­i­ta­tion In­ven­to­ry to­tal score — in one study but missed in the sec­ond, though the drug did achieve the key sec­ondary end­point as­sess­ing the sever­i­ty of ag­i­ta­tion.

Is it enough for an ap­proval?

Lund­beck didn’t spell out the da­ta, which makes this too tough to call. Reg­u­la­tors have been sig­nal­ing their flex­i­bil­i­ty when it comes to Alzheimer’s, a field which has seen noth­ing but fail­ure for dis­ease mod­i­fy­ing and symp­to­matic drugs over the last 15 years. So it’s a pos­si­bil­i­ty. With Rex­ul­ti on the mar­ket al­ready, and like­ly in use for de­men­tia-re­lat­ed ag­i­ta­tion, an­a­lysts were ex­pect­ing a clear win. But it may just come down to the safe­ty pro­file.

“Im­por­tant­ly, in the two Rex­ul­ti stud­ies over­all mor­tal­i­ty was low (0.86%) with no deaths con­sid­ered to be treat­ment re­lat­ed,” not­ed Jef­feries’ Pe­ter Welford. He added:

Lund­beck and part­ner Ot­su­ka plan to meet with the FDA to dis­cuss these Rex­ul­ti da­ta. Typ­i­cal­ly we be­lieve reg­u­la­to­ry au­thor­i­ties re­quire two pos­i­tive stud­ies to sup­port ap­proval but we note equiv­o­cal study out­comes are com­mon in CNS in­di­ca­tions. Fur­ther­more, no drugs are US ap­proved specif­i­cal­ly to treat ag­i­ta­tion as­so­ci­at­ed with de­men­tia, de­spite the wide­spread use of an­tipsy­chotics. Rex­ul­ti’s com­par­a­tive­ly clean safe­ty pro­file could po­ten­tial­ly al­lay class-wide con­cerns and nu­mer­ous ini­tia­tives are on­go­ing to de­crease the off-la­bel use of an­tipsy­chotics in nurs­ing homes.

One like­ly line that the com­pa­nies will take fo­cus­es on their take­away that the da­ta var­ied by coun­try. The da­ta sep­a­ra­tion be­tween place­bo and drug was par­tic­u­lar­ly poor in Rus­sia, they said, which could be due to stan­dard of care rather than the qual­i­ty of the med­i­cine. Rus­sia and East­ern Eu­rope have been reg­u­lar­ly held out as prob­lem­at­ic lo­ca­tions for drug tri­als, which makes you won­der why Lund­beck and Ot­su­ka’s team de­cid­ed to in­clude the coun­try in a world­wide tri­al in the first place.

It will be up to the FDA now to sig­nal which way this ap­pli­ca­tion could go.

The two part­ners have been vexed by Alzheimer’s, like most oth­er com­pa­nies in this field. They re­cent­ly wrote off their 5HT6 symp­to­matic drug af­ter it flopped in stud­ies. An­tipsy­chotics, though, are not your run-of-the-mill kind of Alzheimer’s drug, open­ing up some new op­por­tu­ni­ties to fol­low.

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.