Shoot­ing for a new stan­dard on os­teoarthri­tis, Mer­ck KGaA out­lines promis­ing da­ta for a po­ten­tial game-chang­er

Mer­ck KGaA’s phar­ma group is tak­ing one more step in a long jour­ney to­ward re­hab­bing its rep in the R&D field this week­end. Com­pa­ny ex­ecs turned up at the ACR sci­en­tif­ic con­fer­ence in San Diego to roll out a promis­ing look at some key Phase II os­teoarthri­tis da­ta — which comes with a crit­i­cal caveat.

The drug is sprifer­min, which Mer­ck Serono has had in its pipeline for the past 13 years af­ter bag­ging it from Zy­mo­Ge­net­ics, now a part of Bris­tol-My­ers Squibb. In the first two-year ef­fi­ca­cy as­sess­ment of the five-year study, re­searchers are now proud­ly point­ing to a slight in­crease of car­ti­lage in the knee, as op­posed to the re­morse­less de­cline that leads to ex­pen­sive knee re­place­ment surgery.

Lu­ciano Ros­set­ti

By Mer­ck re­search chief Lu­ciano Ros­set­ti’s reck­on­ing, this is the first time a drug has ac­tu­al­ly trig­gered a re­ver­sal of this dis­ease — rather than just man­ag­ing the symp­toms of the dis­ease — leav­ing the Ger­man Mer­ck with a po­ten­tial­ly ground­break­ing drug in a field that ac­counts for 5% of the world’s pop­u­la­tion, with 237 mil­lion peo­ple whose lives have been crimped by this dis­ease.

“The most strik­ing re­sponse is the dis­ease re­sponse,” Ros­set­ti tells me. And what’s par­tic­u­lar­ly ex­cit­ing, he added, is that the drug — re­com­bi­nant hu­man FGF-18 pro­tein — is not just block­ing the de­cline of car­ti­lage, but sig­nif­i­cant­ly build­ing nor­mal car­ti­lage in a 2-year time frame.

At the high­est dosage, re­searchers tracked a 0.05 mm in­crease in car­ti­lage thick­ness, with a step down in dose to a 0.04 mm in­crease. Con­sid­er­ing that a 0.04 mm loss puts pa­tients at a great­ly high­er risk of knee re­place­ment, he says, they’re look­ing at a ma­jor treat­ment shift.

If the da­ta are borne out in Phase III, Mer­ck KGaA be­lieves it can line up an­oth­er drug be­hind its big PD-1 drug avelum­ab, part­nered with Pfiz­er in the biggest up­front ever record­ed in biotech. Mer­ck KGaA al­so re­cent­ly won a Eu­ro­pean ap­proval for the MS drug cladrib­ine, ini­tial­ly aban­doned in 2010 af­ter it was spurned by reg­u­la­tors on both sides of the At­lantic. That marked a low point for Mer­ck KGaA, which went for more than a decade with­out a sin­gle ma­jor win on the R&D side of the busi­ness.

Ros­set­ti and the rest of the team want to put the bad old days be­hind the com­pa­ny for good, and sprifer­min could help.

But there’s a big catch. The drug failed to reg­is­ter any kind of no­tice­able im­prove­ment over place­bo on pa­tients’ symp­toms in­volv­ing pain or func­tion, an es­sen­tial part of the sec­ondary end­point pro­file.

Just get­ting an in­jec­tion of ei­ther place­bo or drug in the knee had a big im­pact, says Ros­set­ti, mak­ing it im­pos­si­ble to tease out the drug’s ef­fect. They now have to see if reg­u­la­tors are open to us­ing a mark­er on car­ti­lage thick­ness rather than an ef­fect on symp­toms as a Phase III pri­ma­ry end­point.

There is no set plan for Phase III, he adds, with up­com­ing reg­u­la­to­ry ex­changes need­ed to sort out tri­al de­sign and length. You can be sure it won’t be easy or quick, though. Glob­al­Da­ta re­cent­ly es­ti­mat­ed that the drug could hit the mar­ket in 2021, with fair­ly lim­it­ed near-term com­mer­cial prospects in a mar­ket dom­i­nat­ed by cheap gener­ics.

Still, it’s for­ward progress for Mer­ck KGaA in the clin­ic. And that is big.

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.

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 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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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.

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.

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.

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.