FDA out­lines a laun­dry list of sur­ro­gate end­points with an eye to ex­pand­ing the ros­ter for drug de­vel­op­ers

The FDA on Wednes­day pub­lished a list of sur­ro­gate end­points to help in­form drug de­vel­op­er dis­cus­sions with rel­e­vant Cen­ter for Bi­o­log­ics Eval­u­a­tion and Re­search (CBER) or Cen­ter for Drug Eval­u­a­tion and Re­search (CDER) re­view di­vi­sions.

The list, which was cre­at­ed thanks to the 21st Cen­tu­ry Cures Act, in­cludes sur­ro­gate end­points that spon­sors have used as pri­ma­ry ef­fi­ca­cy clin­i­cal tri­al end­points for ap­proval of new drug ap­pli­ca­tions (NDAs) or bi­o­log­ics li­cense ap­pli­ca­tions (BLAs). It al­so in­cludes sur­ro­gate end­points that may be ap­pro­pri­ate for use as pri­ma­ry ef­fi­ca­cy clin­i­cal tri­al end­points for drug or bi­o­log­ic ap­provals, al­though they have not yet been used to sup­port an ap­proved NDA or BLA.

The list, which will be up­dat­ed every six months, fea­tures sur­ro­gate end­points for nu­mer­ous dis­eases in­clud­ing acromegaly, dif­fer­ent can­cers, chron­ic kid­ney dis­ease, cys­tic fi­bro­sis, he­pati­tis A, B and C, HIV, hy­per­ten­sion and os­teo­poro­sis, among oth­ers.

“The ac­cept­abil­i­ty of these sur­ro­gate end­points for use in a par­tic­u­lar drug or bi­o­log­ic de­vel­op­ment pro­gram will be de­ter­mined on a case-by-case ba­sis,” the FDA said.

The list, which sep­a­rates adult and pe­di­atric end­points, does not in­clude com­pos­ite end­points that are a com­bi­na­tion of bio­mark­er sur­ro­gate end­points and clin­i­cal end­points. The ta­ble al­so does not in­clude sur­ro­gate end­points that may have been ac­cept­ed for past drug de­vel­op­ment pro­grams but are no longer ac­cept­able as an end­point to sup­port reg­is­tra­tion.

And crit­ics of the list note a lack of speci­fici­ty.

Vinay Prasad

Vinay Prasad, as­so­ciate pro­fes­sor of med­i­cine at Ore­gon Health and Sci­ence Uni­ver­si­ty, told Fo­cus: “I would say, at least for can­cer, it is done at such a high lev­el with so lit­tle de­tail, it is pret­ty much use­less. A bet­ter sum­ma­ry of sur­ro­gates used to jus­ti­fy ap­provals and their strength can be found in our pa­per from the Mayo clin­ic pro­ceed­ings…We are show­ing the sur­ro­gate used by ap­proval, the path­way of ap­proval, and the strength of the sur­ro­gate in the bio­med­ical lit­er­a­ture. They just say what sur­ro­gates are used in what tu­mors, but do not ex­plain the line of ther­a­py, the drugs that uti­lized the path­way or the strength of cor­re­la­tion.”

Back­ground

Ac­cord­ing to sec­tion 507(e)(9) of the Food Drug & Cos­met­ic Act, “[t]he term ‘sur­ro­gate end­point’ means a mark­er, such as a lab­o­ra­to­ry mea­sure­ment, ra­di­ograph­ic im­age, phys­i­cal sign, or oth­er mea­sure, that is not it­self a di­rect mea­sure­ment of clin­i­cal ben­e­fit, and (A) is known to pre­dict clin­i­cal ben­e­fit and could be used to sup­port tra­di­tion­al ap­proval of a drug or bi­o­log­i­cal prod­uct; or (B) is rea­son­ably like­ly to pre­dict clin­i­cal ben­e­fit and could be used to sup­port the ac­cel­er­at­ed ap­proval of a drug or bi­o­log­i­cal prod­uct in ac­cor­dance with sec­tion 506(c).”


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 news@raps.org for more in­for­ma­tion. 

Author

Zachary Brennan

managing editor, RAPS

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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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.

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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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.

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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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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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.”

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.