Al­ny­lam slammed af­ter pa­tient death forces in­ves­ti­ga­tors to halt dos­ing of fi­tusir­an, rais­ing new safe­ty fears

Al­ny­lam $AL­NY has been slammed by an­oth­er round of safe­ty fears, forced to sus­pend all treat­ment with fi­tusir­an af­ter a pa­tient died from a blood clot in a Phase II he­mo­phil­ia A study.

Al­ny­lam ex­ecs plan to re­sume dos­ing as soon as pos­si­ble, but the com­pa­ny has been hob­bled by deaths be­fore that re­cent­ly KO’d a top pro­gram at the RNAi group. New safe­ty ques­tions about a key late-stage drug like this is the last thing that Al­ny­lam wants to grap­ple with now.

Al­ny­lam will now put plans to start the Phase III AT­LAS study on hold un­til this is re­solved, with the on­go­ing Phase II OLE study side­lined for now. And shares of the biotech dropped 11% on the news Thurs­day morn­ing.

There’s no telling how deep the dam­age could be, though. As Paul Mat­teis at Leerink not­ed, blood clot­ting has been a con­cern for some time among the thought lead­ers in the field. And even if Al­ny­lam gets past this hur­dle, an in­ci­dent like this could crip­ple mar­ket ex­pec­ta­tions.

While we look to more col­or re­gard­ing AL­NY’s pre­lim­i­nary plans on the com­pa­ny’s call this morn­ing, our ini­tial re­ac­tion is that even if the dos­ing and late stage pro­grams are re­sumed for fi­tusir­an, the com­mer­cial op­por­tu­ni­ty may now be lim­it­ed giv­en the risk-averse na­ture of the he­mo­phil­ia pa­tient pop­u­la­tion (es­pe­cial­ly pa­tients with­out in­hibitors).

The in­ci­dent be­gan when a pa­tient com­plained of ex­er­cise-in­duced hip pain fol­lowed by a se­vere headache. He was di­ag­nosed with a sub­arach­noid he­m­or­rhage on the ba­sis of CT imag­ing and treat­ed with fac­tor VI­II con­cen­trate ad­min­is­tered two to three times dai­ly.

Four­teen days af­ter he was ad­mit­ted to the hos­pi­tal, he died from cere­bral ede­ma. And the cause of death was de­ter­mined to be cere­bral ve­nous si­nus throm­bo­sis, hit­ting a si­nus which drains blood from the brain, not a sub­arach­noid he­m­or­rhage — trig­ger­ing the fear that the clot was trig­gered by the ther­a­py.

The set­back oc­curs just 10 months af­ter Sanofi agreed to pay $100 mil­lion to opt in on the Phase III fi­tusir­an study af­ter part­ner­ing with Al­ny­lam in a $700 mil­lion buy-in back in 2014. Two months ago the part­ners re­port­ed en­cour­ag­ing da­ta from the Phase II tri­al.

Al­ny­lam is no stranger to safe­ty scares and con­cerns about killing pa­tients with its RNAi tech. Last fall the biotech was forced to scrap its sec­ond most ad­vanced drug — re­vusir­an — af­ter re­searchers tracked an im­bal­ance in the num­ber of deaths be­tween the drug arm and the con­trol group. That oc­curred just days af­ter Al­ny­lam took a nasty hit on its stock price af­ter a much ear­li­er-stage drug, the RNAi liv­er dis­ease drug ALN-AAT, was scrapped af­ter three pa­tients ex­pe­ri­enced spik­ing liv­er en­zymes in a Phase I/II.

“We are deeply sad­dened to learn of this pa­tient’s death, and we ex­tend our sym­pa­thies to his fam­i­ly,” said Ak­shay Vaish­naw, ex­ec­u­tive vice pres­i­dent of R&D at Al­ny­lam. “We be­lieve that fi­tusir­an holds great promise as a po­ten­tial treat­ment op­tion for pa­tients with he­mo­phil­ia, and we re­main ful­ly com­mit­ted to its on­go­ing de­vel­op­ment. Fol­low­ing fur­ther in­ves­ti­ga­tion of this safe­ty find­ing, im­ple­men­ta­tion of a risk mit­i­ga­tion strat­e­gy, and align­ment with glob­al reg­u­la­to­ry au­thor­i­ties, we ex­pect to re­sume fi­tusir­an dos­ing in our clin­i­cal stud­ies as soon as pos­si­ble, po­ten­tial­ly as ear­ly as late 2017, with a goal of ad­vanc­ing this in­no­v­a­tive in­ves­ti­ga­tion­al med­i­cine to he­mo­phil­ia pa­tients in need.”

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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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.)

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.

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.

Gene ther­a­pies seize the top of the list of the most ex­pen­sive drugs on the plan­et — and that trend has just be­gun

Anyone looking for a few simple reasons why the gene therapy field has caught fire with the pharma giants need only look at the new list of the 10 most expensive therapies from GoodRx.

Two recently approved gene therapies sit atop this list, with Novartis’ Zolgensma crowned the king of the priciest drugs at $2.1 million. Right below is Luxturna, the $850,000 pioneer from Spark, which Roche is pushing hard to acquire as it adds a gene therapy group to the global mix.

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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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