Study repli­cates piv­otal tri­al re­sults us­ing 're­al world ev­i­dence'

A study pub­lished in JA­MA In­ter­nal Med­i­cine on Mon­day was able to repli­cate the re­sults of a large ran­dom­ized con­trolled clin­i­cal tri­al for the blood pres­sure drug telmis­ar­tan us­ing so-called re­al world ev­i­dence gath­ered from in­sur­ance claims da­ta.

The goal of the study, which was con­duct­ed by re­searchers at Har­vard Med­ical School, was to in­ves­ti­gate whether health care data­bas­es can be used to con­firm find­ings from clin­i­cal tri­als con­duct­ed to sup­port ad­di­tion­al in­di­ca­tions for al­ready ap­proved drugs.

In re­cent years, the FDA has stepped up its ef­forts to ad­vance the use of da­ta gath­ered from “re­al world” sources, such as in­sur­ance claims da­ta, elec­tron­ic health records, and pa­tient reg­istries in its de­ci­sion mak­ing.

His­tor­i­cal­ly, FDA’s use of re­al world ev­i­dence has fo­cused on iden­ti­fy­ing and as­sess­ing safe­ty is­sues for mar­ket­ed prod­ucts, but re­cent­ly lead­ers at the agency have sug­gest­ed re­al world ev­i­dence (RWE) could be used to sup­port new in­di­ca­tions or la­bel ex­pan­sions for drugs, and in June the agency ex­pand­ed the use of Ed­wards Life­sciences’ Sapi­en 3 tran­scatheter aor­tic valve based on da­ta gath­ered from a pa­tient reg­istry.


To con­duct the study the au­thors looked at anonymized in­sur­ance claims da­ta for some 64,000 pa­tients that were avail­able be­fore the sup­ple­men­tal in­di­ca­tion for telmis­ar­tan was ap­proved for pa­tients new­ly pre­scribed ei­ther telmis­ar­tan or ramipril, an­oth­er drug used to treat high blood pres­sure.

The piv­otal study, known as On­go­ing Telmis­ar­tan Alone and in Com­bi­na­tion with Ramipril Glob­al End-point Tri­al (ON­TAR­GET), was con­duct­ed to de­ter­mine whether telmis­ar­tan is non­in­fe­ri­or to ramipril in pre­vent­ing car­dio­vas­cu­lar events and to see whether the com­bi­na­tion of the two drugs is su­pe­ri­or to ramipril alone.

“Among pa­tients new­ly pre­scribed telmis­ar­tan and ramipril be­fore the FDA’s de­ci­sion to ap­prove a sup­ple­men­tal in­di­ca­tion for telmis­ar­tan, we found re­sults that were al­most iden­ti­cal to those of the ran­dom­ized clin­i­cal tri­al that led to telmis­ar­tan’s sup­ple­men­tal in­di­ca­tion,” the au­thors write.

The au­thors say the study shows promise as a way to re­duce the amount of time and mon­ey spent to sup­port sup­ple­men­tal in­di­ca­tions for some drugs. While ON­TAR­GET took sev­en years to com­plete and cost tens of mil­lions of dol­lars, the au­thors say their study was com­plet­ed in just 12 weeks and at a hun­dredth of the cost.

But while the au­thors were able to con­firm the re­sults of ON­TAR­GET with their co­hort study, they note that do­ing so for sup­ple­men­tal in­di­ca­tions for most drugs would not be fea­si­ble.

From 2005-2014 the au­thors iden­ti­fied 138 new in­di­ca­tions for drugs ap­proved by FDA, more than three-quar­ters (78%) of which were grant­ed based on a pri­ma­ry out­come that would not be iden­ti­fi­able in ex­ist­ing health­care data­bas­es, such as pathol­o­gy re­sults or changes in clin­i­cal scores.

“The fact that our case study bol­stered the con­clu­sions of a tri­al de­signed to iden­ti­fy a sup­ple­men­tal in­di­ca­tion for a mar­ket­ed med­ica­tion and was done rel­a­tive­ly ef­fi­cient­ly us­ing avail­able da­ta sets, rig­or­ous epi­demi­o­log­ic meth­ods, and mod­ern soft­ware plat­forms sup­ports the con­cept of con­duct­ing sim­i­lar data­base analy­ses as part of rou­tine prac­tice for man­u­fac­tur­ers sub­mit­ting ap­pli­ca­tions for sup­ple­men­tal in­di­ca­tions to the FDA,” the au­thors write, not­ing that FDA could fa­cil­i­tate the use of such stud­ies by pro­vid­ing guid­ance on they are ap­pro­pri­ate.

First pub­lished here. Reg­u­la­to­ry Fo­cus is the flag­ship on­line pub­li­ca­tion of the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety (RAPS), the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care and re­lat­ed prod­ucts, in­clud­ing med­ical de­vices, phar­ma­ceu­ti­cals, bi­o­log­ics and nu­tri­tion­al prod­ucts. Email for more in­for­ma­tion.

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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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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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.”

UP­DAT­ED: Chica­go biotech ar­gues blue­bird, Third Rock 'killed' its ri­val, pi­o­neer­ing tha­lassemia gene ther­a­py in law­suit

Blue­bird bio $BLUE chief Nick Leschly court­ed con­tro­ver­sy last week when he re­vealed the com­pa­ny’s be­ta tha­lassemia treat­ment will car­ry a jaw-drop­ping $1.8 mil­lion price tag over a 5-year pe­ri­od in Eu­rope — mak­ing it the plan­et’s sec­ond most ex­pen­sive ther­a­py be­hind No­var­tis’ $NVS fresh­ly ap­proved spinal mus­cu­lar at­ro­phy ther­a­py, Zol­gens­ma, at $2.1 mil­lion. A Chica­go biotech, mean­while, has been fum­ing at the side­lines. In a law­suit filed ear­li­er this month, Er­rant Gene Ther­a­peu­tics al­leged that blue­bird and ven­ture cap­i­tal group Third Rock un­law­ful­ly prised a vi­ral vec­tor, de­vel­oped in part­ner­ship with the Memo­r­i­al Sloan Ket­ter­ing Can­cer Cen­ter (MSK), from its grasp, and thwart­ed the de­vel­op­ment of its sem­i­nal gene ther­a­py.

Neil Woodford. Woodford Investment Management via YouTube

Wood­ford braces po­lit­i­cal storm as UK fi­nan­cial reg­u­la­tors scru­ti­nize fund sus­pen­sion

The shock of Neil Wood­ford’s de­ci­sion to block with­drawals for his flag­ship fund is still rip­pling through the rest of his port­fo­lio — and be­yond. Un­der po­lit­i­cal pres­sure, UK fi­nan­cial reg­u­la­tors are now tak­ing a hard look while in­vestors con­tin­ue to flee.

In a re­sponse let­ter to an MP, the Fi­nan­cial Con­duct Au­thor­i­ty re­vealed that it’s opened an in­ves­ti­ga­tion in­to the sus­pen­sion fol­low­ing months of en­gage­ment with Link Fund So­lu­tions, which tech­ni­cal­ly del­e­gat­ed Wood­ford’s firm to man­age its funds.

Gilead baits new al­liance with $45M up­front, div­ing in­to the busy pro­tein degra­da­tion field

Gilead is jump­ing on board the pro­tein degra­da­tion band­wag­on. And they’re turn­ing to a low-pro­file Third Rock start­up for the ex­per­tise. But if you were look­ing for a trans­for­ma­tion­al deal to kick up fresh en­thu­si­asm for Gilead, you’ll have to re­main pa­tient.

This one will have a long way to go be­fore they get in­to the clin­ic.

The big biotech said Wednes­day morn­ing that it is pay­ing $45 mil­lion up­front and re­serv­ing a whop­ping $2.3 bil­lion in biotech bucks if San Fran­cis­co-based Nurix can point the way to new can­cer ther­a­pies, as well as drugs for oth­er, un­spec­i­fied dis­eases.

A new num­ber 1 drug? Keytru­da tapped to top the 10 biggest block­busters on the world stage by 2024

Analysts may be fretting about Keytruda’s longterm prospects as a host of rival therapies elbow their way to the market. But the folks at Evaluate Pharma are confident that last year’s $7 billion earner is headed for glory, tapping it to beat out the current #1 therapy Humira as AbbVie watches that franchise swoon over the next 5 years.

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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.

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.