FDA, NIH look to stream­line over­sight of gene ther­a­pies

The FDA and NIH are propos­ing to fur­ther lim­it the role of the NIH and its Re­com­bi­nant DNA Ad­vi­so­ry Com­mit­tee (RAC) in the re­view of hu­man gene ther­a­pies.

The changes, an­nounced in the Fed­er­al Reg­is­ter on Thurs­day, are aimed at re­duc­ing over­laps in the two agen­cies’ over­sight of gene ther­a­pies which re­sult in du­plica­tive work for spon­sors as the field pro­gress­es fol­low­ing the ap­proval of the first three gene ther­a­pies last year.

Scott Got­tlieb

In an ac­com­pa­ny­ing per­spec­tive by FDA Com­mis­sion­er Scott Got­tlieb and NIH Di­rec­tor Fran­cis Collins in the New Eng­land Jour­nal of Med­i­cine, the two agency heads write that there is no longer a com­pelling need to sub­ject gene ther­a­pies to ad­di­tion­al over­sight com­pared to oth­er types of bio­med­ical prod­ucts.

“In the view of the se­nior lead­ers of the FDA and the NIH, there is no longer suf­fi­cient ev­i­dence to claim that the risks of gene ther­a­py are en­tire­ly unique and un­pre­dictable—or that the field still re­quires spe­cial over­sight that falls out­side our ex­ist­ing frame­work for en­sur­ing safe­ty,” they write.

Cur­rent­ly, spon­sors of clin­i­cal tri­als in­volv­ing gene ther­a­pies are re­quired to sub­mit ini­tial pro­to­cols, an­nu­al re­ports, amend­ments and se­ri­ous ad­verse event re­ports to both agen­cies.

Fran­cis Collins

His­tor­i­cal­ly, the RAC al­so played a role in re­view­ing gene ther­a­py pro­to­cols and safe­ty da­ta aris­ing from such stud­ies, though in 2016 the NIH lim­it­ed the com­mit­tee’s role to pro­to­cols “that raised ex­cep­tion­al is­sues or con­cerns” based on a rec­om­men­da­tion from the In­sti­tute of Med­i­cine. Ac­cord­ing to the NIH, the RAC has on­ly re­viewed three of the 275 gene ther­a­py pro­to­cols sub­mit­ted since that change took ef­fect.

How­ev­er, un­der the FDA and NIH’s pro­pos­al, the RAC’s role in re­view­ing gene ther­a­py pro­to­cols would be en­tire­ly elim­i­nat­ed and spon­sors would no longer be re­quired to sub­mit re­ports to NIH on such pro­to­cols.

Ad­di­tion­al­ly, the NIH says it will re­vise the roles of In­sti­tu­tion­al Biosafe­ty Com­mit­tees (IBCs), which are tasked with lo­cal over­sight of stud­ies in­volv­ing re­com­bi­nant or syn­thet­ic nu­cle­ic acid mol­e­cules, to en­sure their over­sight of hu­man gene ther­a­py pro­to­cols is con­sis­tent with oth­er re­search sub­ject to the NIH Guide­lines.

Ac­cord­ing to Got­tlieb and Collins, ad­vances in the gen­er­al frame­work for clin­i­cal tri­al and med­ical prod­uct over­sight and the cre­ation of Clin­i­cal­Tri­als.gov have re­duced the need for spe­cial over­sight for gene ther­a­pies.

The two al­so cite oth­er ef­forts, such as re­vi­sions to the Com­mon Rule and the FDA’s re­lease of draft guid­ance on man­u­fac­tur­ing is­sues, long-term fol­low up and clin­i­cal de­vel­op­ment path­ways for gene ther­a­pies, as re­duc­ing the need for spe­cial over­sight of gene ther­a­py pro­to­cols by the NIH.

“Even as our un­der­stand­ing of gene ther­a­py has ad­vanced, so has our gen­er­al frame­work for med­ical prod­uct safe­ty. The tools we use to ad­dress oth­er ar­eas of sci­ence are now well suit­ed to gene ther­a­py,” they write.

Go­ing for­ward, the NIH says the RAC will con­tin­ue to func­tion as an ad­vi­so­ry board to the NIH on emerg­ing fields such as gene edit­ing, syn­thet­ic bi­ol­o­gy and neu­rotech­nol­o­gy.


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. 

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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Step­ping on Roche's toes, Mer­ck cuts in­to SCLC niche with third-line Keytru­da OK

In the in­creas­ing­ly crowd­ed check­point race, small cell lung can­cer has been a rare area where Roche, a sec­ond run­ner-up, has a lead over the en­trenched lead­ers Mer­ck and Bris­tol-My­ers Squibb. But Mer­ck is fi­nal­ly mak­ing some head­way in that di­rec­tion with the lat­est ap­proval for its PD-1 star.

The lat­est green light en­dors­es Keytru­da in the third-line treat­ment of metasta­t­ic SCLC, where it would be giv­en to pa­tients whose dis­ease ei­ther don’t re­spond to or re­lapse af­ter chemother­a­py, which would have fol­lowed at least one pri­or line of ther­a­py.

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.