FDA de­vel­op­ing guid­ance on re­al-world da­ta qual­i­ty is­sues, of­fi­cials say

As the FDA grap­ples with how to use re­al-world da­ta for reg­u­la­to­ry de­ci­sions, two FDA of­fi­cials wrote in a per­spec­tive pub­lished last Fri­day in the Clin­i­cal Jour­nal of the Amer­i­can So­ci­ety of Nephrol­o­gy that the agency is de­vel­op­ing guid­ance on da­ta qual­i­ty is­sues unique to the re­al-world da­ta set­ting and re­lat­ed study de­sign con­sid­er­a­tions.

Al­iza Thomp­son and Mary Ross South­worth of the Di­vi­sion of Car­dio­vas­cu­lar and Re­nal Prod­ucts with­in FDA’s Cen­ter for Drug Eval­u­a­tion and Re­search (CDER) ex­plain: “Al­though the FDA has ex­pe­ri­ence us­ing ob­ser­va­tion­al (non­in­ter­ven­tion­al) study de­signs in the post­mar­ket set­ting to eval­u­ate prod­uct risks in broad pop­u­la­tions, us­ing non­ran­dom­ized method­olo­gies to de­ter­mine ef­fec­tive­ness can be prob­lem­at­ic be­cause of con­cerns about the abil­i­ty to ad­e­quate­ly con­trol for con­found­ing, se­lec­tion bias, and the pos­si­bil­i­ty of mis­clas­si­fi­ca­tion er­ror.”

New da­ta stan­dards will need to be de­vel­oped and the FDA is “cur­rent­ly ex­plor­ing,” they write, when the use of ob­ser­va­tion­al da­ta “may be ap­pro­pri­ate for eval­u­at­ing ef­fec­tive­ness from a broad pol­i­cy per­spec­tive and al­so, as in­di­vid­ual drug man­u­fac­tur­ers sub­mit pro­pos­als for us­ing re­al world da­ta to sup­port mar­ket­ing ap­pli­ca­tions.”

The draft guid­ance in de­vel­op­ment is not on CDER’s 2019 guid­ance agen­da, but the FDA did pub­lish draft guid­ance in May on re­al-world ev­i­dence (RWE) sub­mis­sions. Last De­cem­ber, the agency al­so re­leased its frame­work for the use of RWE.

“There is wide­spread recog­ni­tion that there will be a learn­ing curve and that demon­stra­tion projects will play a crit­i­cal role in defin­ing how and when re­al world da­ta and re­al world ev­i­dence can be used,” Thomp­son and South­worth add.

Kid­ney Dis­ease

They al­so dis­cuss how re­al-world da­ta and RWE could pro­vide a way to ac­cel­er­ate the de­vel­op­ment of ther­a­pies that im­prove the lives of pa­tients with kid­ney dis­ease.

“Many have not­ed the po­ten­tial to in­te­grate RCTs [ran­dom­ized con­trolled tri­als] in­to the da­ta-rich clin­i­cal care set­ting of pa­tients on dial­y­sis, and ef­forts are un­der­way to un­der­stand and ad­dress cur­rent chal­lenges to do­ing so,” they ex­plain. “In RCTs of pa­tients with com­mon kid­ney dis­eases, such as di­a­bet­ic kid­ney dis­ease, re­al world da­ta could be used to fa­cil­i­tate the iden­ti­fi­ca­tion and en­roll­ment of pa­tients in­to tri­als. Study method­olo­gies aimed at cap­tur­ing key ef­fi­ca­cy out­comes us­ing both tra­di­tion­al meth­ods, and elec­tron­ic health records or claims da­ta could pro­vide in­sight in­to the chal­lenges and op­por­tu­ni­ties of us­ing re­al world da­ta to as­sess out­comes of in­ter­est by en­abling a com­par­i­son be­tween the two.”

But they warn that giv­en the “size of the pop­u­la­tion with stage 4 and 5 CKD [chron­ic kid­ney dis­ease] and frag­men­ta­tion of health care among var­i­ous US health care sys­tems, suc­cess­ful use of such da­ta will like­ly re­quire col­lab­o­ra­tion among re­searchers and the ag­gre­ga­tion of re­al world da­ta from mul­ti­ple sources. How­ev­er, these nov­el ap­proach­es should not sup­plant larg­er ef­forts to in­clude these pop­u­la­tions in reg­is­tra­tion tri­als for drugs, where ap­pro­pri­ate, or con­duct ded­i­cat­ed RCTs in these pop­u­la­tions.”

RAPS: First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.


Zachary Brennan

managing editor, RAPS

UP­DAT­ED: Akcea’s top 3 C-suite ex­ecs are chopped out as Io­n­is sends in an in­ter­im quar­ter­back from their bench

The top 3 execs running Ionis’ majority-owned spinoff Akcea are hitting the exit in a surprise twist Monday morning.

Akcea $AKCA reported this morning that CEO Paula Soteropoulos, President Sarah Boyce and COO Jeffrey Goldberg are out in a clean sweep. The board has placed Damien McDevitt — the chief business officer on the mother ship — in the interim chief executive spot as they hunt for some permanent replacements. Michael J. Yang and Joseph ‘Skip’ Klein III, meanwhile have joined the company’s board of directors,

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 60,300+ biopharma pros reading Endpoints daily — and it's free.

Irene Frachon at the courthouse. (Michel Euler via AP Images)

Servi­er be­gins manslaugh­ter tri­al over weight loss drug

French pharma Servier begins trial today, as the company stands accused of manslaughter and deceit over a diabetes weight loss drug linked to as many as 2,000 deaths.

The drug, Mediator (benfluorex), was pulled out of French pharmacies in 2009 after 33 years on the market. A year later, the French medicine safety agency announced the drug was suspected of causing multiple deaths, sparking outrage, a criminal investigation and a series of reforms to the country’s system of regulating the pharmaceutical industry.

As­traZeneca vet heads to UK biotech as the new CSO; Mallinck­rodt touts pos­i­tive PhI­II da­ta

→ UK-based early cancer detection company Oncimmune Holdings has welcomed Tariq Sethi as CSO, Matthew Luttrell as CMO and Cléa Rosenfeld as head of investor relations. Sethi is a professor of respiratory medicine at King’s College London. Before jumping on board at Oncimmune, Sethi was chief physician-scientist, vice president in the clinical discovery unit at AstraZeneca. He is also the founder of Galecto Biotech. Luttrell joins the company after a stint as head of hematology, growth and emerging markets at Shire (now Takeda). He’s served in other roles at Eli Lilly, Novo Nordisk, Gilead, and GSK. Rosenfeld brings experience to her new role from her time as head of investor relations at Shire, where she helped bring the company from a FTSE 250 Company to a top 50 FTSE company.

FDA puts the brakes on a rare dis­ease biotech’s PhI­II as reg­u­la­tors wait for an up­date — shares crum­ble

Little Abeona Therapeutics $ABEO is back in trouble this morning.

The biotech reported that the FDA is slamming the brakes on their Phase III study of EB-101 for rare cases of recessive dystrophic epidermolysis bullosa, which is characterized by fragile skin that blisters quickly.

The drug uses gene transfer to deliver COL7A1 genes into a patient’s own skin cells, which are then put back into the patient’s skin for improved wound healing. It has RMAT and breakthrough status at the FDA but doesn’t have approval for the Phase III.

A long-suf­fer­ing Clo­vis makes a leap in­to ra­dio­phar­ma­ceu­ti­cals, pay­ing $12M in cash to beef up the pipeline

In the 17 months since Clovis won an approval for their PARP drug Rubraca, the reality of anemic sales revenue against a backdrop of major league competition has crushed its shares and raised doubts about its future. So now it’s going about the business of adding new candidates to the pipeline that might help inspire some renewed enthusiasm for the company.

Monday morning Clovis reported that it is handing over $12 million in upfront payments to Berlin-based 3B Pharmaceuticals to nab rights to preclinical radiopharmaceuticals. And the Boulder, CO-based biotech says it plans to steer the first drug to the clinic in the second half of next year.

UP­DAT­ED: Here comes the oral GLP-1 drug for di­a­betes — and No­vo Nordisk wants to price Ry­bel­sus 'at a sim­i­lar lev­el as Ozem­pic'

Novo Nordisk’s priority review voucher on oral semaglutide has paid off. The FDA approval for the GLP-1 drug hit late Friday morning, around six months after the NDA filing.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 60,300+ biopharma pros reading Endpoints daily — and it's free.

As Nas­daq en­rolls the fi­nal batch of 2019 IPOs, how have the num­bers com­pared to past years?

IGM Biosciences’ upsized IPO haul, coming after SpringWorks’ sizable public debut, has revved up some momentum for the last rush of biotech IPOs in 2019.

With 39 new listings on the books and roughly two more months to go before winding down, Nasdaq’s head of healthcare listings Jordan Saxe sees the exchange marking 50 to 60 biopharma IPOs for the year.

“December 15 is usually the last possible day that companies will price,” he said, as companies get ready for business talks at the annual JP Morgan Healthcare Conference in January.

That won’t come close to the record-setting numbers last year — the government shutdown at the beginning of the year was partly to blame — but it’s good enough to be at least on par with the few years before.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 60,300+ biopharma pros reading Endpoints daily — and it's free.

David Grainger [file photo]

'Dis­con­nect the bas­tard­s' — one biotech's plan to break can­cer cell­s' uni­fied de­fens­es

Chemotherapy and radiotherapy are the current gladiators of cancer treatment, but they come with well-known limitations and side-effects. The emergence of immunotherapy — a ferocious new titan in oncologist’s toolbox — takes the brakes off the immune system to kill cancer cells with remarkable success in some cases, but the approach is not always effective. What makes certain forms of cancer so resilient? Scientists may have finally pieced together a tantalizing piece of the puzzle, and a new biotech is banking on a new approach to fill the gap.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 60,300+ biopharma pros reading Endpoints daily — and it's free.

A fa­vorite in Alex­ion’s C-suite is leav­ing, and some mighty sur­prised an­a­lysts aren’t the least bit hap­py about it

Analysts hate to lose a biotech CFO they’ve come to trust and admire — especially if they’re being blindsided by a surprise exit.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 60,300+ biopharma pros reading Endpoints daily — and it's free.