Pfiz­er ax­es a key Duchenne MD pro­gram af­ter PhII flop, rais­ing new doubts for a drug cat­e­go­ry that at­tract­ed Roche and Bio­gen

Pfiz­er is jet­ti­son­ing an­oth­er dis­ap­point­ing drug that’s been in the clin­ic for Duchenne mus­cu­lar dy­s­tro­phy. The phar­ma gi­ant says it’s ax­ing work on do­ma­grozum­ab (PF-06252616) — rais­ing the odds against one R&D fo­cus in the field that has at­tract­ed some mar­quee play­ers around the world.

The drug is one of sev­er­al de­signed to in­hib­it myo­statin, which flopped against a one-year test of mus­cle strength, fail­ing to help pa­tients to any sig­nif­i­cant de­gree. By sup­press­ing myo­statin, which blunts mus­cles, the the­o­ry is that a prop­er ther­a­py can help slow the mus­cle-wast­ing ail­ment that in­evitably proves fa­tal to the boys who in­her­it this dis­ease.

Seng Cheng

The fail­ure elim­i­nates one of sev­er­al an­ti-myo­statin ther­a­pies, in­clud­ing BMS-986089, a drug which Bris­tol-My­ers sold to Roche in the spring of 2017 for $170 mil­lion in cash and $205 mil­lion in mile­stones. That drug — now called RG6206 (RO7239361) — is in a Phase II/III study.

Just a month ago Bio­gen al­so got in­to the myo­statin game, pay­ing $27 mil­lion in cash to grab a Phase Ia drug called ALG-801 (BI­IB110) and a pre­clin­i­cal drug ALG-802 from Alive­G­en. Bio­gen not­ed at the time that the two drugs “rep­re­sent nov­el ways of tar­get­ing the myo­statin path­way, which is one of the most thor­ough­ly stud­ied ap­proach­es for mus­cle en­hance­ment.” These ther­a­pies are de­signed to tar­get the nys­tatin path­way, which Bio­gen be­lieves could work bet­ter than oth­er drugs in the clin­ic.

There’s noth­ing un­usu­al about fail­ure in this field, though, where Duchenne MD has proven a tough ob­jec­tive. No­var­tis ex­pe­ri­enced a late-stage set­back with their myo­statin drug bima­grum­ab (BYM338) in 2016. Atara–an Am­gen ($AMGN) spin­off–saw its clin­i­cal can­di­date PIN­TA 745 fail a Phase II study for pro­tein en­er­gy wast­ing in pa­tients with end-stage re­nal dis­ease, forc­ing the biotech to halt de­vel­op­ment ef­forts and switch fo­cus to can­cer. Back in 2011, Ac­celeron ($XL­RN) and Shire ($SH­PG) al­so halt­ed clin­i­cal work on ACE-031, an­oth­er myo­statin drug with big dreams in fight­ing mus­cle wast­ing, then de­cid­ed to scrap it al­to­geth­er in 2013 af­ter run­ning some ad­di­tion­al pre­clin­i­cal tests.

It’s just as bad in oth­er re­lat­ed mus­cle drug fields. Two months ago shares of Sum­mit were crushed in the wake of their failed Phase II for a utrophin mod­u­la­tor, ezutro­mid.

Duchenne MD has al­so been a mine field of con­tro­ver­sy in R&D. Sarep­ta gained an ap­proval for eteplirsen, with­out con­vinc­ing reg­u­la­tors it ac­tu­al­ly works. Now the biotech has been shift­ing at­ten­tion to its gene ther­a­py — put on hold re­cent­ly due to im­pu­ri­ties found in a third-par­ty pro­vid­ed plas­mid — which has looked promis­ing at the very ear­li­est stages of track­ing pa­tient re­spons­es. PTC, mean­while, has been pur­su­ing an FDA OK for ataluren, ap­proved in Eu­rope de­spite re­peat­ed fail­ures in the clin­ic. 

Not to be over­looked is Schol­ar Rock, where the ex­ec­u­tive team be­lieves they can find suc­cess by tar­get­ing la­tent rather than ac­tive myo­statin. The biotech, though, felt the heat Thurs­day morn­ing, with its shares plung­ing 12% on the news. That set­back trig­gered a flur­ry of de­fen­sive posts from an­a­lysts de­fend­ing Schol­ar Rock and bur­nish­ing their chances, with one less ri­val to wor­ry about.

Pfiz­er hasn’t quite giv­en up on its drug, leav­ing the door open to fu­ture tri­als in mus­cu­lar dis­eases. But its big re­main­ing ef­fort in DMD is in a gene ther­a­py pro­gram it has un­der­way for PF-06939926, an AAV de­liv­ered treat­ment which car­ries a short­ened ver­sion of the hu­man dy­s­trophin gene (mi­ni-dy­s­trophin).

“We are dis­ap­point­ed by these re­sults and while we are not pro­gress­ing with the stud­ies, the da­ta will con­tribute to a greater un­der­stand­ing of this dis­ease and we will eval­u­ate the to­tal da­ta set to see if there is a place for this med­i­cine in mus­cu­lar dis­eases,” said Seng Cheng, the CSO for the Pfiz­er Rare Dis­ease Re­search Unit.

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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Arc­turus ex­pands col­lab­o­ra­tion, adding $30M cash; Ku­ra shoots for $100M raise

→  Rare dis­ease play­er Ul­tragenyx $RARE is ex­pand­ing its al­liance with Arc­turus $ARCT, pay­ing $24 mil­lion for eq­ui­ty and an­oth­er $6 mil­lion in an up­front as the two part­ners ex­pand their col­lab­o­ra­tion to in­clude up to 12 tar­gets. “This ex­pand­ed col­lab­o­ra­tion fur­ther so­lid­i­fies our mR­NA plat­form by adding ad­di­tion­al tar­gets and ex­pand­ing our abil­i­ty to po­ten­tial­ly treat more dis­eases,” said Emil Kakkis, the CEO at Ul­tragenyx. “We are pleased with the progress of our on­go­ing col­lab­o­ra­tion. Our most ad­vanced mR­NA pro­gram, UX053 for the treat­ment of Glyco­gen Stor­age Dis­ease Type III, is ex­pect­ed to move in­to the clin­ic next year, and we look for­ward to fur­ther build­ing up­on the ini­tial suc­cess of this part­ner­ship.”

UP­DAT­ED: Chica­go biotech ar­gues blue­bird, Third Rock 'killed' its ri­val, pi­o­neer­ing tha­lassemia gene ther­a­py in law­suit

Blue­bird bio $BLUE chief Nick Leschly court­ed con­tro­ver­sy last week when he re­vealed the com­pa­ny’s be­ta tha­lassemia treat­ment will car­ry a jaw-drop­ping $1.8 mil­lion price tag over a 5-year pe­ri­od in Eu­rope — mak­ing it the plan­et’s sec­ond most ex­pen­sive ther­a­py be­hind No­var­tis’ $NVS fresh­ly ap­proved spinal mus­cu­lar at­ro­phy ther­a­py, Zol­gens­ma, at $2.1 mil­lion. A Chica­go biotech, mean­while, has been fum­ing at the side­lines. In a law­suit filed ear­li­er this month, Er­rant Gene Ther­a­peu­tics al­leged that blue­bird and ven­ture cap­i­tal group Third Rock un­law­ful­ly prised a vi­ral vec­tor, de­vel­oped in part­ner­ship with the Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter (MSK), from its grasp, and thwart­ed the de­vel­op­ment of its sem­i­nal gene ther­a­py.

Neil Woodford. Woodford Investment Management via YouTube

Wood­ford braces po­lit­i­cal storm as UK fi­nan­cial reg­u­la­tors scru­ti­nize fund sus­pen­sion

The shock of Neil Wood­ford’s de­ci­sion to block with­drawals for his flag­ship fund is still rip­pling through the rest of his port­fo­lio — and be­yond. Un­der po­lit­i­cal pres­sure, UK fi­nan­cial reg­u­la­tors are now tak­ing a hard look while in­vestors con­tin­ue to flee.

In a re­sponse let­ter to an MP, the Fi­nan­cial Con­duct Au­thor­i­ty re­vealed that it’s opened an in­ves­ti­ga­tion in­to the sus­pen­sion fol­low­ing months of en­gage­ment with Link Fund So­lu­tions, which tech­ni­cal­ly del­e­gat­ed Wood­ford’s firm to man­age its funds.

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.