Al­ny­lam spot­lights just how good the ef­fi­ca­cy da­ta are for givosir­an — tamp­ing down on safe­ty con­cerns

Al­ny­lam $AL­NY took an­oth­er turn on its tran­si­tion lap to a ful­ly fledged com­mer­cial biotech to­day, post­ing its de­tailed — and very promis­ing — ef­fi­ca­cy da­ta for their RNAi drug givosir­an while hop­ing to tamp down the fret­ting over safe­ty is­sues that spoiled their ear­li­er top-line an­nounce­ment.

We knew go­ing in­to the Eu­ro­pean As­so­ci­a­tion for the Study of the Liv­er meet­ing in Vi­en­na that the drug had a great p val­ue — now backed up by a 90% me­di­an re­duc­tion in at­tacks of acute he­pat­ic por­phyr­ia, a painful and de­bil­i­tat­ing ill­ness with no cur­rent­ly ap­proved ther­a­pies. Half of the pa­tients end­ed at­tack free, which would make this a no-brain­er for reg­u­la­tors.

What rat­tled some of the an­a­lysts last time was that the rate of se­ri­ous ad­verse events in the drug arm was more than twice what was seen in the place­bo group. A se­ri­ous safe­ty sig­nal could ham­per or tor­pe­do any drug, and in­deed we learned that sev­er­al of the pa­tients ex­pe­ri­enced se­ri­ous is­sues trig­gered by the ther­a­py. Specif­i­cal­ly, this in­volved cas­es of chron­ic kid­ney dis­ease, pyrex­ia and ab­nor­mal liv­er func­tion test.

Al­ny­lam CEO John Maraganore, though, says that with this drug for this dis­ease in these pa­tients, it will pass muster to soon be­come Al­ny­lam’s sec­ond ap­proved ther­a­py — a land­mark event for a com­pa­ny that has be­come a stan­dard-set­ter for many of the de­vel­op­ment-stage com­pa­nies hop­ing to tran­si­tion in­to mar­ket­ing one day.

Al­ny­lam CEO John Maraganore Get­ty Im­ages

Click on the im­age to see the full-sized ver­sion


“This is a dis­ease that’s about as bad as it gets,” Maraganore told me in a pre­view of to­day’s pre­sen­ta­tion. “It is a ter­ri­ble, ter­ri­ble dis­ease, and ob­vi­ous­ly when you look at the ben­e­fit it’s pret­ty over­whelm­ing.”

Maraganore knows that 2 cas­es of CKD won’t go un­no­ticed by any­one, but in bal­anc­ing the risk/ben­e­fit, he says there’s no doubt that the drug will get a green light. Be­sides, he adds, these pa­tients typ­i­cal­ly have a high risk of kid­ney dis­ease and liv­er is­sues, which reg­u­la­tors will cer­tain­ly take in­to ac­count.

As for pa­tients, he says, the da­ta speak for them­selves, with 93 of 94 pa­tients go­ing on to en­roll in the ex­ten­sion pe­ri­od of the study.

“We couldn’t be more hap­py about the da­ta,” he adds. “If my daugh­ter had this dis­ease I wouldn’t hes­i­tate for a nanosec­ond” to get her on the drug. And then he threw his moth­er and him­self in­to that sce­nario. 

Every­body gets the drug.

That has Jef­feries? Mau­ry Ray­croft fore­cast­ing $600 mil­lion in peak sales by 2030. He adds:

For us, there were no sur­pris­es at EASL, and as a re­sult we are more con­fi­dent in gi­vo’s over­all pro­file and po­ten­tial. The ph.III in­ves­ti­ga­tor and AL­NY be­lieve the drug can be used broad­ly in AHP; add’ly, both AL­NY and the in­ves­ti­ga­tor an­tic­i­pate re­sults will con­tin­ue to im­prove.

Some of the ob­servers ear­li­er al­so weren’t too hap­py about a mixed set of sec­ondary end­points, with the ther­a­py scor­ing for sev­er­al bio­mark­ers of the dis­ease but falling short of sta­tis­ti­cal sig­nif­i­cance on sec­on­daries like pain and fa­tigue and nau­sea, what pa­tients are feel­ing.

Maraganore con­ced­ed those points but coun­tered that you don’t have to hit every sec­ondary to get an ap­proval — true enough — and that a set of pa­tient-re­port­ed out­comes in­di­cat­ed that 89% re­port­ed an im­prove­ment on ther­a­py com­pared to 37% on place­bo.

Maraganore is like­ly right about the caveats. No ther­a­py is per­fect, and reg­u­la­tors will bend over back­wards on side ef­fects if they can get a treat­ment for this dis­ease. That leaves Al­ny­lam com­ing out of EASL with a time­line that an­tic­i­pates an ap­proval by this time next year.

As of now, they’re odds-on fa­vorites for an ap­proval.


Im­age: Kristof­fer Trip­plaar for SIPA AP

The top 10 block­buster drugs in the late-stage pipeline — Eval­u­ate adds 6 new ther­a­pies to heavy-hit­ter list

Vertex comes in for a substantial amount of criticism for its no-holds-barred tactical approach toward wresting the price it wants for its commercial drugs in Europe. But the flip side of that coin is a highly admired R&D and commercial operation that regularly wins kudos from analysts for their ability to engineer greater cash flow from the breakthrough drugs they create.

Both aspects needed for success in this business are on display in the program backing Vertex’s triple for cystic fibrosis. VX-659/VX-445 + Tezacaftor + Ivacaftor — it’s been whittled down to 445 now — was singled out by Evaluate Pharma as the late-stage therapy most likely to win the crown for drug sales in 5 years, with a projected peak revenue forecast of $4.3 billion.

The latest annual list, which you can see here in their latest world preview, includes a roster of some of the most closely watched development programs in biopharma. And Evaluate has added 6 must-watch experimental drugs to the top 10 as drugs fail or go on to a first approval. With apologies to the list maker, I revamped this to rank the top 10 by projected 2024 sales, instead of Evaluate's net present value rankings.

It's how we roll at Endpoints News.

Here is a quick summary of the rest of the top 10:

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John Reed at JPM 2019. Jeff Rumans for Endpoints News

Sanofi's John Reed con­tin­ues to re­or­ga­nize R&D, cut­ting 466 jobs while boost­ing can­cer, gene ther­a­py re­search

The R&D reorganization inside Sanofi is continuing, more than a year after the pharma giant brought in John Reed to head the research arm of the Paris-based company.
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How small- to mid-sized biotechs can adopt pa­tient cen­tric­i­ty in their on­col­o­gy tri­als

By Lucy Clos­sick Thom­son, Se­nior Di­rec­tor of On­col­o­gy Pro­ject Man­age­ment, Icon

Clin­i­cal tri­als in on­col­o­gy can be cost­ly and chal­leng­ing to man­age. One fac­tor that could re­duce costs and re­duce bar­ri­ers is har­ness­ing the pa­tient voice in tri­al de­sign to help ac­cel­er­ate pa­tient en­roll­ment. Now is the time to adopt pa­tient-cen­tric strate­gies that not on­ly fo­cus on pa­tient needs, but al­so can main­tain cost ef­fi­cien­cy.

In­vestor day prep at Mer­ck in­cludes a new strat­e­gy to pick up the pace on M&A — re­port

Mer­ck’s re­cent deals to buy up two bolt-on biotechs — Ti­los and Pelo­ton — weren’t an aber­ra­tion. In­stead, both ac­qui­si­tions mark a new strat­e­gy to beef up its dom­i­nant can­cer drug op­er­a­tions cen­tered on Keytru­da while look­ing to ad­dress grow­ing con­cerns that too many of its eggs are in the one I/O bas­ket for their PD-1 pro­gram. And Mer­ck is go­ing af­ter more small- and mid-sized buy­outs to calm those fears.

John Chiminski, Catalent CEO - File Photo

'It's a growth play': Catal­ent ac­quires Bris­tol-My­er­s' Eu­ro­pean launch pad, ex­pand­ing glob­al CD­MO ops

Catalent is staying on the growth track.

Just two months after committing $1.2 billion to pick up Paragon and take a deep dive into the sizzling hot gene therapy manufacturing sector, the CDMO is bouncing right back with a deal to buy out Bristol-Myers’ central launchpad for new therapies in Europe, acquiring a complex in Anagni, Italy, southwest of Rome, that will significantly expand its capacity on the continent.

There are no terms being offered, but this is no small deal. The Anagni campus employs some 700 staffers, and Catalent is planning to go right in — once the deal closes late this year — with a blueprint to build up the operations further as they expand on oral solid, biologics, and sterile product manufacturing and packaging.

This is an uncommon deal, Catalent CEO John Chiminski tells me. But it offers a shortcut for rapid growth that cuts years out of developing a green fields project. That’s time Catalent doesn’t have as the industry undergoes unprecedented expansion around the world.

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Partners Innovation Fund

David de Graaf now has his $28.5M launch round in place, build­ing a coen­zyme A plat­form in his lat­est start­up

Long­time biotech ex­ec David de Graaf has the cash he needs to set up the pre­clin­i­cal foun­da­tion for his coen­zyme A me­tab­o­lism com­pa­ny Comet. A few high-pro­file in­vestors joined the ven­ture syn­di­cate to sup­ply Comet with $28.5 mil­lion in launch mon­ey — enough to get it two years in­to the plat­form-build­ing game, with­in knock­ing dis­tance of the clin­ic.

Canaan jumped in along­side ex­ist­ing in­vestor Sofinno­va Part­ners to co-lead the round, with par­tic­i­pa­tion by ex­ist­ing in­vestor INKEF Cap­i­tal and new in­vestor BioIn­no­va­tion Cap­i­tal.

Dave Barrett, Brian Chee, Amir Nashat, Amy Schulman. Polaris

Bob Langer's first port of call — Po­laris Part­ners — maps $400M for ninth fund

Health and tech ven­ture group Po­laris Part­ners, which counts Alec­tor, Al­ny­lam and Ed­i­tas Med­i­cine as part of its port­fo­lio, is set­ting up its ninth fund, rough­ly two years af­ter it closed Po­laris VI­II with $435 mil­lion in the bank, sur­pass­ing its tar­get by $35 mil­lion.

The Boston-based firm, in an SEC fil­ing, said it in­tends to raise $400 mil­lion for the fund. Po­laris — which rou­tine­ly backs com­pa­nies mold­ed out of the work done in the lab of pro­lif­ic sci­en­tist Bob Langer of MIT  — typ­i­cal­ly in­vests ear­ly, and sticks around till com­pa­nies are in the green. Like its peers at Flag­ship and Third Rock, Po­laris is all about cham­pi­oning the lo­cal biotech scene with a steady flow of start­up cash.

Right back at you, Pfiz­er: BeiGene and a Pfiz­er spin­out launch a new­co to de­vel­op a MEK/BRAF in­hibitor that could ri­val $11.4B com­bo

A day af­ter Pfiz­er bought Ar­ray and its ap­proved can­cer com­bo, BeiGene and Pfiz­er spin­out Spring­Works have part­nered in launch­ing a new biotech that has an eye on the very same mar­ket the phar­ma gi­ant just paid bil­lions for. And they’re plan­ning on us­ing an ex-Pfiz­er drug to do it.

In a nut­shell, Chi­na’s BeiGene is toss­ing in a pre­clin­i­cal BRAF in­hibitor — BGB-3245, which cov­ers both V600 and non-V600 BRAF mu­ta­tions — for a big stake in a new, joint­ly con­trolled biotech called Map­Kure with Bain-backed Spring­Works.

Sanofi aligns it­self with Google to stream­line drug de­vel­op­ment

Tech­nol­o­gy is bleed­ing in­to health­care, and big phar­ma is rid­ing the wave. Sanofi $SNY ap­point­ed its first chief dig­i­tal of­fi­cer this Feb­ru­ary, fol­low­ing the foot­steps of its peers. By May, the French drug­mak­er and some of its big phar­ma com­pa­tri­ots joined forces with Google par­ent Al­pha­bet’s Ver­i­ly unit to aug­ment clin­i­cal tri­al re­search. On Tues­day, the Parisian com­pa­ny tied up with Google to ac­cess its cloud com­put­ing and ar­ti­fi­cial in­tel­li­gence tech to spur the de­vel­op­ment of new ther­a­pies.