Avro­bio takes a sec­ond stab at a good first im­pres­sion — but dura­bil­i­ty ques­tions still dog gene ther­a­py

Ge­off MacK­ay

Four months ago, Avro­bio’s shares $AVRO were sub­ject­ed to a rit­u­al slaugh­ter on Wall Street af­ter in­vestors were spooked by their lead gene ther­a­py’s poor per­for­mance on a key mea­sure re­flect­ing po­ten­tial dura­bil­i­ty. To­day, the top ex­ecs at the com­pa­ny are mak­ing a new pitch, hop­ing that they can win over the mar­ket with up­dat­ed ev­i­dence that the gene ther­a­py is work­ing for pa­tients with Fab­ry dis­ease.

But you can ex­pect plen­ty of more ques­tions to come on its longterm prospects.

The big ques­tion last Oc­to­ber was cen­tered on the vec­tor copy num­bers re­flect­ed in the hand­ful of pa­tients who had re­ceived Avro­bio’s AVR-RD-01. The VCN is a mark­er for the gene ther­a­py’s abil­i­ty to in­sert healthy copies of the GLA gene that en­codes for a de­fi­cient en­zyme in Fab­ry dis­ease. And it has to be right in a field pur­su­ing once-and-done treat­ments. Blue­bird went back to the draw­ing board af­ter track­ing VCN num­bers of 0.3 and 0.6 in the first gen­er­a­tion of its gene ther­a­py for be­ta-tha­lassemia, herald­ing a spike to 1.5 and 2.1 for two pa­tients in a Lenti-Glo­bin study. And blue­bird knows full well that a high­er, or ris­ing, VCN breeds con­fi­dence.

In Avro­bio’s case, the VCN head­ed down in sev­er­al cas­es. And their re­lease un­der­scores that adding a few months of ob­ser­va­tion didn’t im­prove mat­ters.  

Ac­cord­ing to CEO Ge­off MacK­ay, who de­cid­ed to add the VCN num­bers to this morn­ing’s re­lease in­stead of wait­ing for the evening pre­sen­ta­tion of the da­ta for an­a­lysts, this was all “as ex­pect­ed.” Pa­tient #1’s VCN, he said in an email, is “sta­ble” at 0.1.

In the Oc­to­ber re­sults we saw:

Pa­tient #1 start­ed ther­a­py with a VCN of 0.7 and then re­searchers tracked a steady drop to 0.1 18 months post-treat­ment. Pa­tient #2 dropped from 1.4 to 0.4 in 6 months. Pa­tient #3: 0.2 to 0.8 at 3 months. And pa­tient #4 went from 0.7 to 0.5 in a few months.

In the up­date to­day Pa­tient #1’s VCN is still at 0.1 22 months af­ter treat­ment. Pa­tient #2 is still at 0.4 at 12 months and Pa­tient #3 dropped to 0.5 at 6 months. Pa­tient #1 in the Phase II is at 0.2 at 6 months, drop­ping from 0.5 at 3 months af­ter start­ing out at 0.2.

The biotech set out to high­light the bio­mark­er ev­i­dence to back up their ther­a­py’s abil­i­ty to sub­sti­tute the chron­ic use of en­zyme re­place­ment ther­a­py for Fab­ry. The com­pa­ny not­ed:

All (evalu­able) pa­tients with re­port­ed da­ta ex­hib­it AGA en­zyme ac­tiv­i­ty above the di­ag­nos­tic range for males with clas­sic Fab­ry dis­ease af­ter re­ceiv­ing AVR-RD-01, in­clud­ing at 22 months for Pa­tient 1 of the Phase 1 study.

Two of the pa­tients in the Phase I have sus­pend­ed use of ERT.

We’ll see how in­vestors think about that now. But you can ex­pect plen­ty of ques­tions ahead on moves the com­pa­ny is mak­ing to im­prove the VCN rank­ings.

As of yes­ter­day’s close Avro­Bio’s shares were down 70% from their high of $51 last fall. The stock was tread­ing wa­ter at the open this morn­ing, slight­ly in the red dur­ing mid-morn­ing trad­ing.

In starved an­tibi­ot­ic field, Melin­ta soars as FDA grants speedy drug re­view

Such is the state of af­fairs in an­tibi­ot­ic land that the FDA agree­ing to pri­or­i­ty re­view an ap­pli­ca­tion to ex­pand the use of an an­tibi­ot­ic can rock­et up a stock more than two-fold.

On Wednes­day, Melin­ta Ther­a­peu­tics said its ap­proved an­tibi­ot­ic Baxdela had been grant­ed pri­or­i­ty re­view for use in com­mu­ni­ty-ac­quired bac­te­r­i­al pneu­mo­nia (CAPB). The FDA is ex­pect­ed to make its de­ci­sion by Oc­to­ber 24. Shares of the Con­necti­cut drug­mak­er $ML­NT cat­a­pult­ed, clos­ing up near­ly 224% at $6.41.

Ken Frazier 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

Who’s next in line to suc­ceed Ken Fra­zier as CEO of the Keytru­da-blessed Mer­ck?

When Merck waved off a looming forced retirement for Ken Frazier last September, the board cited flexibility in CEO transition as a key factor in the decision. Having Frazier — who’s also chairman of the company — around beyond his 65th birthday in 2019 would ensure they install the best person at the best time, they said.

The board has evidently begun that process with a clear preference for internal candidates, sources told Bloomberg. CFO Robert Davis, chief marketing officer Michael Nally, and chief commercial officer Frank Clyburn are all in the running, according to an insider.

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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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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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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.

Brent Saunders at an Endpoints News event in 2017 — File photo

An­a­lyst call with Al­ler­gan ex­ecs stokes an­tic­i­pa­tion of a plan to split the com­pa­ny in ‘a month or two’

So what’s up at Al­ler­gan?

Ear­li­er this week the ubiq­ui­tous Ever­core ISI an­a­lyst Umer Raf­fat was on the line with com­pa­ny ex­ec­u­tives to probe in­to the lat­est on the num­bers as well as CEO Brent Saun­ders’ re­cent de­c­la­ra­tion that he’d be do­ing some­thing de­fin­i­tive to help long-suf­fer­ing in­vestors who have watched their shares dwin­dle in val­ue.

He came away with the im­pres­sion that a sig­nif­i­cant com­pa­ny split is on the way. And not on some dis­tant time hori­zon.

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.