Safe­ty threat forces FDA to put a hold on Re­gen­eron, Te­va’s big NGF pain drug fas­inum­ab

George Yan­copou­los, Re­gen­eron

Just one month af­ter Te­va agreed to pay Re­gen­eron $250 mil­lion in cash to part­ner on its NGF pain pro­gram, the FDA has slapped a clin­i­cal hold on their Phase IIb study of fas­inum­ab for low­er back pain.

The hold was trig­gered af­ter a pa­tient in the study suf­fer­ing from ad­vanced os­teoarthri­tis de­vel­oped a case of ad­ju­di­cat­ed arthropa­thy – joint dis­ease. And the new part­ners are coun­ter­ing the hold by plan­ning to ex­clude os­teoarthri­tis pa­tients from a planned Phase III.

The deal be­tween the two com­pa­nies, which al­so in­clud­ed $2.3 bil­lion in mile­stones, was the lat­est in a se­ries of ad­vance­ments in the late-stage field. And the hold rais­es old fears that these drugs could de­stroy pa­tients’ joints.

NGF drugs were all the rage un­til five years ago, when some of the pa­tients in clin­i­cal stud­ies be­gan to blow out their joints with meds de­signed to si­lence nerve growth fac­tors. The safe­ty is­sues side­lined the drugs, once tapped as like­ly block­busters, but de­vel­op­ers slow­ly worked out a plan to pro­tect pa­tients, and Pfiz­er got back in­to the clin­ic, with Eli Lil­ly sign­ing on to part­ner in a $1.8 bil­lion deal. J&J came back in right along­side, with fal­ranum­ab, in-li­censed from Am­gen.

Even though J&J had a huge Phase III ef­fort un­der­way, with four late-stage stud­ies, the phar­ma gi­ant de­cid­ed to aban­don the work ear­li­er this year, say­ing on­ly that it was repri­or­i­tiz­ing its pipeline.

In­ves­ti­ga­tors on the fas­inum­ab pro­gram say that as a re­sult of the FDA de­ci­sion they com­plet­ed an un­planned in­ter­im re­view of the da­ta that showed “clear ev­i­dence of ef­fi­ca­cy.” But at least one an­a­lyst says that the set­back may spur sec­ond thoughts at Te­va, which is still on the hook for pay­ing half of a bil­lion-dol­lar Phase III pro­gram.

“Te­va has paid $250M up­front to REGN, but the more se­ri­ous cash out­lays are yet to hap­pen (i.e., Ph 3 out­comes),” notes Umer Raf­fat at Ever­core ISI.  “This may be a good time to cut the loss­es – es­pe­cial­ly with this new up­date on clin­i­cal hold (does it trig­ger some “MAC” clause?).”

And Ge­of­frey Porges at Leerink was with­er­ing in his as­sess­ment of the drug, which he is now writ­ing off as a com­plete loss:

Based on this hold, and the his­to­ry of the class, we are re­duc­ing our prob­a­bil­i­ty of suc­cess to ze­ro, and re­mov­ing all fas­inum­ab rev­enue (and fu­ture mile­stones) from our mod­el and REGN val­u­a­tion. The hold is for the low back pain pro­gram (phase IIb) but al­so in­volves ad­di­tion­al scruti­ny and changes to the de­vel­op­ment plans for the os­teoarthri­tis pro­gram as well. We be­lieve that these dis­clo­sures sug­gest that fas­inum­ab will have all of the li­a­bil­i­ties of pri­or drugs in this class, and will face the same re­peat­ed de­lays, in­creased scruti­ny and la­belling lim­i­ta­tions that plagued oth­er pro­grams in the same class.

The NGF tar­get has re­mained a tempt­ing field in pain R&D, es­pe­cial­ly as fresh alarms over the epi­dem­ic of opi­oid ad­dic­tion rais­es fears from coast-to-coast in the US. Find­ing a new way to treat pain with­out opi­oids would open up a big mar­ket, as reg­u­la­tors look for al­ter­na­tives that can re­place ad­dic­tive treat­ments. And the Re­gen­eron/Te­va team are com­mit­ted to mak­ing their drug work.

“We are mak­ing da­ta-dri­ven de­ci­sions on Phase 3 fas­inum­ab dos­ing that we be­lieve will max­i­mize po­ten­tial ben­e­fit for pa­tients in need, while min­i­miz­ing the like­li­hood of side ef­fects,” said George D. Yan­copou­los, Re­gen­eron’s high pro­file CSO, in a state­ment. “We look for­ward to work­ing with glob­al health au­thor­i­ties to ad­vance this im­por­tant in­ves­ti­ga­tion­al ther­a­py for pa­tients with of­ten dif­fi­cult-to-treat os­teoarthri­tis pain and chron­ic low back pain.”

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.


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.