Armed with up­dat­ed 24-week PhI­II da­ta, GBT con­vinces FDA to re­view sick­le cell drug un­der ac­cel­er­at­ed path­way

In yet an­oth­er sign of the FDA’s en­hanced flex­i­bil­i­ty un­der com­mis­sion­er Scott Got­tlieb, Glob­al Blood Ther­a­peu­tics $GBT has man­aged to con­vinced the reg­u­la­tor to al­low its ex­per­i­men­tal drug, vox­elo­tor, to be eval­u­at­ed un­der the ac­cel­er­at­ed ap­proval path­way for sick­le cell dis­ease (SCD), a group of in­her­it­ed red blood cell dis­or­ders that typ­i­cal­ly af­flict those of African an­ces­try.

SCD im­pacts he­mo­glo­bin, a pro­tein found in red blood cells that car­ries oxy­gen through­out the body, and is char­ac­ter­ized by episodes of sear­ing pain as well as or­gan dam­age.

On Mon­day, the San Fran­cis­co-based biotech said the FDA had agreed to let it ap­ply for vox­elo­tor’s ap­proval un­der this fast-track path­way on the ba­sis of its da­ta from an on­go­ing late-stage study that showed the drug was rais­ing he­mo­glo­bin lev­els, which the com­pa­ny deemed a re­li­able in­di­ca­tor that the once-dai­ly oral ther­a­py would like­ly re­duce the risk of stroke.

Vox­elo­tor is de­signed to work by in­creas­ing he­mo­glo­bin’s affin­i­ty for oxy­gen. SCD pa­tients have atyp­i­cal he­mo­glo­bin mol­e­cules, which can dis­tort red blood cells in­to a sick­le, or cres­cent, shape. Symp­toms such as ane­mia, re­peat­ed in­fec­tions and pe­ri­od­ic episodes of pain, be­gin to ap­pear in ear­ly child­hood. These episodes de­prive the body of oxy­gen-rich blood, which can cul­mi­nate in wide­spread tis­sue and or­gan dam­age, par­tic­u­lar­ly in the lungs, kid­neys, spleen, heart and brain, and dras­ti­cal­ly di­min­ish life ex­pectan­cy.

Ear­li­er this year, the com­pa­ny re­port­ed da­ta from the first tranche of its phase III HOPE study, which showed vox­elo­tor met the main goal of an im­prove­ment in he­mo­glo­bin greater than 1 g/dL with vox­elo­tor 1500 mg, com­pared with place­bo at 12 weeks. As part of ASH, the com­pa­ny pro­vid­ed up­dat­ed 24-week re­sults, which demon­strat­ed the drug con­ferred a sus­tained im­prove­ment in he­mo­glo­bin lev­els.

Da­ta showed that 65% of pa­tients tak­ing vox­elo­tor 1500 mg (p<0.0001) achieved a greater than 1 g/dL in­crease in he­mo­glo­bin at 24 weeks ver­sus 10% of pa­tients on the place­bo. Mean­while, 33% of pa­tients on the low­er 900 mg vox­elo­tor dose achieved (p=0.0159) a sim­i­lar in­crease in he­mo­glo­bin lev­els.

In ad­di­tion, vox­elo­tor ther­a­py was as­so­ci­at­ed with few­er va­so-oc­clu­sive crises (VOCs) – painful com­pli­ca­tions of SCD which oc­cur when sick­le shaped red blood cells get stuck in­side blood ves­sels – de­spite sub­stan­tial in­creas­es in he­mo­glo­bin.

The drug was well tol­er­at­ed with sim­i­lar safe­ty pro­files be­tween the two dos­es, and there was was no ev­i­dence of im­pair­ment of tis­sue oxy­gena­tion at ei­ther dose, the com­pa­ny said.

“These da­ta from the Phase 3 HOPE Study, in­clud­ing the clin­i­cal­ly mean­ing­ful and sta­tis­ti­cal­ly sig­nif­i­cant in­crease in he­mo­glo­bin, have been a key el­e­ment in the dis­cus­sions with the FDA which led to the agency’s agree­ment with GBT’s pro­pos­al for vox­elo­tor un­der the sub­part H ac­cel­er­at­ed ap­proval path­way,” GBT chief Ted Love said in a state­ment.

The com­pa­ny plans to re­quest a pre-NDA meet­ing for the first quar­ter of next year, it said on Mon­day. If ap­proved, it will con­duct a sep­a­rate study post-ap­proval to show the drug can de­fin­i­tive­ly re­duce the risk of stroke.

 

 

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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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.

UP­DAT­ED: Roche fields first ap­proval for Ro­z­lytrek in the run-up to a show­down with Bay­er, Pfiz­er

While it’s wait­ing to hear back from FDA reg­u­la­tors, Roche is be­gin­ning the vic­to­ry lap for en­trec­tinib in Japan.

Roche is giv­ing Bay­er a run for their mon­ey with this tu­mor-ag­nos­tic drug, which tar­gets NTRK gene fu­sions. Now dubbed Ro­z­lytrek, it’s sanc­tioned to treat adult and pe­di­atric pa­tients in Japan with neu­rotroph­ic ty­ro­sine re­cep­tor ki­nase fu­sion-pos­i­tive, ad­vanced re­cur­rent sol­id tu­mors.

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.”