Af­ter se­cur­ing quick OK for PNH pa­tients, Alex­ion's Ul­tomiris suc­ceeds in aHUS piv­otal study

About a month af­ter the FDA gave Alex­ion a Christ­mas present in the form of an ear­ly ap­proval for its rare blood dis­or­der drug, Ul­tomiris, for pa­tients with PNH, the drug­mak­er has re­port­ed pos­i­tive piv­otal da­ta eval­u­at­ing the mon­o­clon­al an­ti­body in a sin­gle-arm study in­volv­ing atyp­i­cal he­molyt­ic ure­mic syn­drome (aHUS) pa­tients.

The Boston-based biotech is now prep­ping reg­u­la­to­ry sub­mis­sions in the Unit­ed States, EU and Japan for Ul­tomiris. The drug is Alex­ion’s shot at pro­tect­ing its block­buster blood dis­or­der fran­chise that is cur­rent­ly cen­tered around its flag­ship drug, Soliris, which is a com­ple­ment in­hibitor typ­i­cal­ly ad­min­is­tered every two weeks. Ul­tomiris has a sim­i­lar mech­a­nism of ac­tion but re­quires less-fre­quent dos­ing — every eight weeks.

aHUS is a chron­ic, pro­gres­sive ul­tra-rare dis­ease that can lead to po­ten­tial­ly ir­re­versible dam­age to kid­neys and oth­er vi­tal or­gans and can be fa­tal. It is char­ac­ter­ized by in­flam­ma­tion and the for­ma­tion of blood clots in small blood ves­sels through­out the body, or throm­bot­ic mi­croan­giopa­thy (TMA).

In the 56-pa­tient late-stage study in­volv­ing adults who had not been pre­vi­ous­ly treat­ed with a com­ple­ment in­hibitor, 53.6% of pa­tients (95% CI [39.6%, 67.5%]) demon­strat­ed com­plete throm­bot­ic mi­croan­giopa­thy (TMA) re­sponse af­ter treat­ment with Ul­tomiris in the ini­tial 26-week treat­ment pe­ri­od — meet­ing the main goal of the study.

Soliris’ la­bel in­di­cates the drug achieved a 56% and 64% TMA re­sponse rate in adult and pe­di­atric aHUS pa­tients.

This da­ta is “broad­ly com­pa­ra­ble to ex­ist­ing Soliris da­ta in sim­i­lar pa­tient pop­u­la­tions, but with added con­ve­nience of every 8 week dos­ing. Alex­ion still has an­oth­er Ul­tomiris phase III study out­stand­ing in pe­di­atric and ado­les­cent aHUS, which is ex­pect­ed in the next few months,” Leerink’s Ge­of­frey Porges wrote in a note.

The news “es­sen­tial­ly de-risks the near term clin­i­cal as­pects of Alex­ion’s life cy­cle man­age­ment strat­e­gy for their $3.5 bil­lion com­ple­ment fran­chise. We ex­pect adop­tion of UIt­o­miris to be even faster in aHUS than PNH giv­en the sub­stan­tial ad­min­is­tra­tive ben­e­fit of Ul­tomiris (Q8 vs Q2 week dos­ing) and the cost sav­ings for pay­ers from Ul­tomiris’ price (~$475,000 vs ~$700,000) com­pared to Soliris.”

In De­cem­ber, Alex­ion said it would price Ul­tomiris at a dis­count to Soliris, which has long been one of the most ex­pen­sive ther­a­pies on the block. In an SEC fil­ing last month, the drug­mak­er dis­closed Ul­tomiris would car­ry a list price of $6,404 per vial, ver­sus Soliris that is priced at $6,543 per vial. The FDA has im­posed a black box warn­ing — the agency’s most se­vere — on both drugs.

The com­pa­ny’s shares $ALXN inched about 3% low­er in ear­ly Mon­day trad­ing. “If in­vestors re­act neg­a­tive­ly to the ap­par­ent sim­i­lar­i­ty of the Ul­tomiris re­sult (54% re­sponse) to the Soliris re­sult in a much ear­li­er tri­al (65% re­sponse) or to the safe­ty events in this study, we would rec­om­mend tak­ing ad­van­tage of that weak­ness giv­en the grow­ing tail val­ue of the com­pa­ny’s fu­ture cash flows,” Porges added.

Cred­it Su­isse’s Mar­tin Auster, in a note ahead of the Phase III re­sults, said he ex­pect­ed a bulk of Soliris pa­tients would switch to Ul­tomiris in the com­ing years.

He mod­elled a rough­ly “80% con­ver­sion from Soliris to Ul­tomiris for the PNH/aHUS fran­chise in 3-4 years in the US/ex-US, re­spec­tive­ly.”

Oth­er drug de­vel­op­ers are al­so de­vel­op­ing treat­ments for the blood dis­or­ders that could po­ten­tial­ly eat in­to sales. But Auster not­ed that aHUS is “a more chal­leng­ing in­di­ca­tion for com­peti­tors to en­roll clin­i­cal tri­als, con­sid­er­ing the dis­ease sever­i­ty, im­por­tance for ear­ly treat­ment to avoid or­gan dam­age, and well-es­tab­lished ef­fi­ca­cy with Soliris. ALXN ben­e­fits from or­phan drug pro­tec­tion in the EU un­til 2023 pos­si­bly push­ing a biosim­i­lar launch in the in­di­ca­tion in­to 2024/2025. The com­pa­ny al­so has com­po­si­tion of mat­ter patents in the US/JP out to 2027.”

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:

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,100+ biopharma pros reading Endpoints daily — and it's free.

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.
Endpoints News

Basic subscription required

Unlock this story instantly and join 53,100+ biopharma pros reading Endpoints daily — and it's free.

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.

Endpoints News

Basic subscription required

Unlock this story instantly and join 53,100+ biopharma pros reading Endpoints daily — and it's free.

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.”