Lethal ex­per­i­men­tal can­cer drug from Han­mi, Boehringer killed three pa­tients — re­port

Ko­re­an health of­fi­cials have tied the deaths of three pa­tients to a can­cer drug launched by Han­mi Phar­ma­ceu­ti­cals and part­nered with Boehringer In­gel­heim, ac­cord­ing to a fol­lowup sto­ry in The Ko­rea Her­ald.

Cit­ing a re­port from the coun­try’s Min­istry of Food and Drug Safe­ty, which was re­leased by Rep. Kwon Mi-hyuk to­day, the three were a 75-year-old pa­tient who died in late 2015, a 57-year-old who died in March and a 54-year-old who died in June.

Al­to­geth­er eight pa­tients died in the study, ac­cord­ing to the Her­ald’s re­port­ing of the min­istry re­view, with 29 “se­ri­ous ad­verse events and ad­verse drug re­ac­tions,” though health of­fi­cials have not con­firmed a link with the drug in every case.

Late Fri­day, Boehringer is­sued a tardy re­sponse to End­points News.

“Boehringer In­gel­heim in­formed reg­u­la­to­ry au­thor­i­ties, in­clud­ing the FDA, about rel­e­vant safe­ty da­ta re­lat­ed to ol­mu­tinib, in­clud­ing side ef­fects such as se­vere skin re­ac­tions men­tioned in the drug safe­ty let­ter,” the com­pa­ny said in a state­ment. “At the same time Boehringer In­gel­heim in­formed all in­ves­ti­ga­tors. We al­so made sure pa­tients re­ceived time­ly com­mu­ni­ca­tions and up­dat­ed their con­sents re­gard­ing these find­ings. We are not aware of any ad­di­tion­al of­fi­cial re­port or com­mu­ni­ca­tion is­sued by the South Ko­re­an Au­thor­i­ty.”

Boehringer In­gel­heim abrupt­ly washed its hand of the drug just days ago with­out ini­tial­ly rais­ing any is­sues with deaths or ad­verse events. Queried by End­points News, a spokesper­son for the com­pa­ny pro­vid­ed a state­ment say­ing that Ko­re­an of­fi­cials had is­sued a let­ter re­fer­ring to “two cas­es of tox­ic epi­der­mal necrol­y­sis, one of them fa­tal, and one case of Stevens-John­son-Syn­drome (non-fa­tal).”

The ap­pro­pri­ate reg­u­la­tors, the com­pa­ny added, had been in­formed of “rel­e­vant safe­ty da­ta re­lat­ed to ol­mu­tinib, in­clud­ing side ef­fects such as se­vere skin re­ac­tions.” Boehringer not­ed that the two cas­es of tox­ic epi­der­mal necrol­y­sis oc­curred in two stud­ies: HM-EM­SI-101 and HM-EM­SI-202. The 101 study is list­ed on clin­i­cal­tri­als.gov as spon­sored by Han­mi with Boehringer cit­ed as a col­lab­o­ra­tor.

Not long ago, though, Boehringer — which has paid Han­mi $65 mil­lion of a $730 mil­lion deal — had been ea­ger to see if it could quick­ly put the drug through a mid-stage study and then seek a fast ap­proval.

Back in May, two months af­ter the sec­ond pa­tient death re­port­ed by Ko­re­an of­fi­cials, Boehringer put out a re­lease tout­ing the Ko­re­an ap­proval of the drug, stat­ing:

Ol­mu­tinib (BI 1482694 / HM61713) is a nov­el third-gen­er­a­tion, oral, EGFR mu­ta­tion-spe­cif­ic TKI. It is cur­rent­ly in ac­cel­er­at­ed de­vel­op­ment through the am­bi­tious ELUXA clin­i­cal tri­al pro­gramme with the aim to sub­mit da­ta and ev­i­dence to the US FDA and EU EMA in 2016. The piv­otal Phase II tri­al ELUXA 1 (HM-EM­SI-202 (NCT02485652) is on­go­ing, en­rolling EGFR T790M mu­ta­tion-pos­i­tive lung can­cer pa­tients who have be­come re­sis­tant to pre­vi­ous TKI treat­ment.

“This first ap­proval of ol­mu­tinib is an ex­cit­ing mile­stone for the com­pound and we are work­ing dili­gent­ly to make this nov­el treat­ment op­tion glob­al­ly avail­able to pa­tients and physi­cians as quick­ly as pos­si­ble,” said Boehringer on­col­o­gy chief Jörg Barth, in a state­ment.

Han­mi, mean­while, is now un­der in­ves­ti­ga­tion to see if there was any in­sid­er trad­ing of com­pa­ny stock around the re­port on ad­verse events, which came out just hours af­ter the com­pa­ny com­plet­ed a tie-up with Genen­tech. In the mean­time, Ko­re­an of­fi­cials have re­port­ed­ly de­cid­ed to keep the drug on the mar­ket un­der the con­di­tion­al ap­proval that was hand­ed out ear­li­er in the year. Even though there was one re­port­ed pa­tient death at the time, they said, they had no di­rect link to the drug. Pa­tients would have to be in­formed of the risks, they said, be­fore they were giv­en the drug.

Look­ing to make a big move in­to brand­ed drugs, Han­mi has been rack­ing up a se­ries of part­ner­ships with mar­quee drug de­vel­op­ers. Just yes­ter­day Genen­tech signed on to part­ner on an ear­ly-stage can­cer drug. Last fall, Sanofi paid €400 mil­lion up­front to part­ner with Han­mi on a port­fo­lio of di­a­betes drugs. Be­fore that, there was a pact with Eli Lil­ly worth up to $690 mil­lion on an au­toim­mune drug for a va­ri­ety of dis­eases. And J&J has al­so part­nered with Han­mi, which has been beef­ing up its R&D arm in a con­cert­ed ef­fort to build a port­fo­lio of brand­ed ther­a­pies.

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.”