Durable, safe and ef­fec­tive long-term kid­ney drug da­ta from Tri­ci­da fu­el block­buster po­ten­tial

Kid­ney drug de­vel­op­er Tri­ci­da’s shares shot up on Thurs­day, af­ter long-term da­ta high­light­ed its lead drug’s durable ef­fi­ca­cy and safe­ty pro­file as a treat­ment for meta­bol­ic aci­do­sis, in which faulty kid­neys are not able to ex­pel the acid caus­ing a buildup in the body.

The drug — TRC101 — is de­signed to bind to hy­drochlo­ric acid in the GI tract, trig­ger­ing the ejec­tion of acid via ex­cre­tion — there­by di­min­ish­ing acid lev­els and stim­u­lat­ing blood bi­car­bon­ate. The com­pa­ny ex­pects to sub­mit an ap­pli­ca­tion to mar­ket the drug by the sec­ond half of this year for the con­di­tion com­mon­ly caused by chron­ic kid­ney dis­ease (and be­lieved to ac­cel­er­ate the pro­gres­sion of CKD), in­crease the risk of mus­cle wast­ing and cause the loss of bone den­si­ty. If ap­proved, it will be the first drug to win the FDA nod specif­i­cal­ly for meta­bol­ic aci­do­sis.

Ger­rit Klaern­er

Da­ta post­ed last June showed the drug in­duced a sta­tis­ti­cal­ly sig­nif­i­cant in­crease in blood bi­car­bon­ate in 208 pa­tients af­ter 12 weeks in a Phase III study, hours af­ter the com­pa­ny ad­ver­tised plans to go pub­lic in a $150 mil­lion IPO. On Thurs­day, Tri­ci­da re­vealed da­ta from a 40-week ex­ten­sion to that study in the 185 pa­tients that com­plet­ed one year as part of the tri­al.

The drug met all the pri­ma­ry and sec­ondary goals of the ex­ten­sion por­tion of the tri­al. The main goal of the ex­ten­sion study was the as­sess­ment of the long-term safe­ty pro­file of TRC101 ver­sus place­bo — and da­ta showed 2.6% of the pa­tients on TRC101 ver­sus 9.8% on place­bo dis­con­tin­ued the 40-week treat­ment pe­ri­od pre­ma­ture­ly.

Sig­nif­i­cant­ly, da­ta on the drug’s dura­bil­i­ty were al­so pos­i­tive. Over 52 weeks, 63% of the 111 TRC101-treat­ed pa­tients ex­hib­it­ed an in­crease in blood bi­car­bon­ate lev­el of at least 4 mil­liequiv­a­lents per liter, or achieved a blood bi­car­bon­ate lev­el in the nor­mal range — com­pared to 38% of the 74 place­bo sub­jects (p=0.0015).

The sta­tis­ti­cal plan al­so called for the eval­u­a­tion of TRC101 ver­sus place­bo for the com­pos­ite end­point of: all-cause mor­tal­i­ty, dial­y­sis/kid­ney trans­plant or a ≥50% de­cline in es­ti­mat­ed glomeru­lar fil­tra­tion rate (a test used to check how well the kid­neys are work­ing) — DD50 when tak­en to­geth­er — over the 52 week pe­ri­od. Of the 124 sub­jects giv­en TRC101, 4% (5) had a DD50 event, in­clud­ing one pa­tient who ini­ti­at­ed dial­y­sis. In con­trast, of the 93 sub­jects ran­dom­ized to the place­bo group, 10.8% (10) sub­jects had a DD50 event, in­clud­ing four deaths and one who ini­ti­at­ed dial­y­sis.

While the tri­al was not pow­ered to as­sess all-cause mor­tal­i­ty and/or the pro­gres­sion of CKD out­comes, Tri­ci­da said it ob­served a 65% re­duc­tion in the an­nu­al­ized event rate of the com­pos­ite end­point of all-cause mor­tal­i­ty and/or the pro­gres­sion of CKD in TRC101-treat­ed sub­jects ver­sus the place­bo group.

“The 52-week…re­sults far ex­ceed­ed our ex­pec­ta­tions,” said com­pa­ny chief Ger­rit Klaern­er said in a state­ment. “We did not an­tic­i­pate that we would ob­serve ev­i­dence of clin­i­cal ben­e­fit be­yond the in­crease in blood bi­car­bon­ate in pa­tients treat­ed with TRC101 un­til the read out of the re­sults of our post­mar­ket­ing tri­al…in the 2022 to 2023 time­frame.”

Shares of the South San Fran­cis­co-based drug de­vel­op­er $TC­DA leapt more than 57% on Thurs­day, clos­ing at $37.80.

Cowen’s Phil Nadeau, who deemed the da­ta ‘im­pres­sive,’ ex­pects TRC101 will achieve $1 bil­lion in rev­enue by 2025.

(T)here is a ma­jor need to con­trol meta­bol­ic aci­do­sis and slow the pro­gres­sion of CKD. Though sodi­um bi­car­bon­ate is ef­fec­tive, its high sodi­um con­cen­tra­tion makes most CKD pa­tients in­el­i­gi­ble for it…With 25 mil­lion peo­ple in the U.S. hav­ing stage 3, 4, or 5 CKD, TRC101 al­so ad­dress­es a large pa­tient pop­u­la­tion, and even mod­est pen­e­tra­tion could yield bil­lions in sales.

(T)he com­pos­ite end­point da­ta com­bined with the phys­i­cal func­tion­ing scores show clear, clin­i­cal­ly mean­ing­ful ben­e­fits to pa­tients. In fact, the dra­mat­ic re­duc­tion in the com­pos­ite end­point im­plies that physi­cians need to treat at most 3 pa­tients in or­der for 1 to de­rive a clin­i­cal­ly mean­ing­ful re­duc­tion in CKD pro­gres­sion.

Sep­a­rate­ly, Tri­ci­da on Thurs­day said it had amend­ed its debt fa­cil­i­ty with Her­cules Cap­i­tal, rais­ing the to­tal amount avail­able to up to $200 mil­lion from the $100 mil­lion agreed in Feb­ru­ary 2018.

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.”