Is FDA too lax with its drug ap­proval stan­dards? Se­nior FDA of­fi­cials dis­cuss

From in­dus­try to acad­e­mia, com­menters have ar­gued that the FDA drug ap­proval stan­dards are be­com­ing in­ap­pro­pri­ate­ly low and that the re­quired postap­proval eval­u­a­tions are ei­ther in­ad­e­quate or left un­done.

But three se­nior FDA of­fi­cials of­fered sev­er­al coun­ter­points on Mon­day at the fifth an­nu­al Bio­phar­ma Con­gress in Wash­ing­ton, DC.

Janet Wood­cock FDA

Janet Wood­cock, di­rec­tor of the FDA’s Cen­ter for Drug Eval­u­a­tion and Re­search, ex­plained that the agency is work­ing on its own analy­ses to pro­vide “a more ro­bust re­sponse” to these cri­tiques. She al­so ex­plained how the high num­ber of ap­provals in re­cent years for rare dis­eases may be in­flu­enc­ing this per­cep­tion of a low­er bar, es­pe­cial­ly as more treat­ments are ap­proved on the ba­sis of a sin­gle-arm study or with an ex­ter­nal con­trol group. In ad­di­tion, she point­ed to the “as­tound­ing­ly” high launch prices for some of these rare dis­ease treat­ments that may al­so be part of the rea­son for the push­back.

“We can’t opine on [prices] but we need to get the facts and fig­ures to­geth­er on the tra­jec­to­ries of what they were and what they are now,” Wood­cock said, not­ing she does not think there are any con­cerns from FDA staff re­lat­ed to ther­a­pies ap­proved with a break­through or oth­er ac­cel­er­at­ed des­ig­na­tion.

Pe­ter Marks FDA

Pe­ter Marks, di­rec­tor of the FDA’s Cen­ter for Bi­o­log­ics Eval­u­a­tion and Re­search (CBER), said he thinks the FDA will “al­ways be crit­i­cized for be­ing too fast or too slow,” and that he’s “try­ing to strike the right bal­ance.” He said it’s been help­ful that with some gene ther­a­pies, “it’s very clear that the out­comes are very ap­par­ent, but the prob­lem is that many are not that clear.”

He al­so said that with some re­gen­er­a­tive med­i­cine prod­ucts, CBER sees the op­po­site ex­treme as the “ther­a­pies that are not ef­fec­tive and they want us to say they are ef­fec­tive.” When the FDA says a prod­uct has the ap­pro­pri­ate ef­fi­ca­cy and safe­ty, “we want peo­ple to put ap­pro­pri­ate­ly placed hope in those prod­ucts,” he added.

But Marks cau­tioned: “If there’s no ef­fi­ca­cy, noth­ing is safe enough,” re­fer­ring to some re­gen­er­a­tive med­i­cine prod­ucts that pa­tients are be­ing charged for but which are in­ef­fec­tive.

He al­so said the FDA may get it wrong oc­ca­sion­al­ly with an ap­proval, echo­ing com­ments made by Act­ing Com­mis­sion­er Ned Sharp­less at lunch with re­gard to ac­cel­er­at­ed ap­provals, but Marks added: “That’s what hap­pens when you’re work­ing at the edge.”

Gideon Blu­men­thal FDA

Gideon Blu­men­thal, deputy di­rec­tor of the FDA’s Of­fice of On­col­o­gy Ex­cel­lence (OCE), added that over­all sur­vival “is the gold stan­dard end­point” for on­col­o­gy drugs, and “that’s what we al­ways want to at­tain but there are cir­cum­stances where pa­tient pop­u­la­tions are get­ting small­er and small­er, and it would be im­pos­si­ble to de­tect over­all sur­vival.”

Marks al­so said that the largest de­vel­op­ment he’s seen re­cent­ly is a tran­si­tion from per­son­al­ized to in­di­vid­u­al­ized med­i­cine.

“We’re un­der­stand­ing the mol­e­c­u­lar mech­a­nisms of dis­ease and var­i­ous in­di­vid­ual char­ac­ter­is­tics of dis­ease that we can tar­get prod­ucts for,” he said, which means a “unique ap­proach to reg­u­la­tion be­cause it’s not mak­ing prod­ucts for tra­di­tion­al clin­i­cal de­vel­op­ment. It’s a dif­fer­ent par­a­digm to find ways to have a pro­to­type prod­uct sup­ple­ment­ed with small changes, or for some prod­ucts they won’t even be li­censed but be per­pet­u­al­ly un­der an IND.”

Marks al­so dis­cussed how the pace of in­no­va­tion right now “is in­cred­i­bly fast – we have to be on top of what’s go­ing on at in­dus­try, aca­d­e­m­ic or­ga­ni­za­tions and in­dus­try or­ga­ni­za­tions. Our re­search teams are go­ing through a hori­zon scan­ning process to con­tin­u­al­ly re­tool with ques­tions,” he added.

But Marks al­so not­ed that CBER is go­ing to need to quick­ly in­crease in size to keep up with the pace of new sub­mis­sions. FDA of­fi­cials have pre­vi­ous­ly said that by 2025, the agency will be ap­prov­ing be­tween 10 and 20 cell and gene ther­a­py prod­ucts an­nu­al­ly.

“We’re lucky to have at­tract­ed some skilled peo­ple, com­mit­ted to gene and cell ther­a­py, but it re­mains a chal­lenge par­tic­u­lar­ly with this growth. I wouldn’t be sur­prised if the cell and gene ther­a­py branch­es need to dou­ble in size over the next three to five years,” Marks said.


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.

Author

Zachary Brennan

managing editor, RAPS

UP­DAT­ED: In a stun­ning turn­around, Bio­gen says that ad­u­canum­ab does work for Alzheimer's — but da­ta min­ing in­cites con­tro­ver­sy and ques­tions

Biogen has confounded the biotech world one more time.

In a stunning about-face, the company and its partners at Eisai say that a new analysis of a larger dataset on aducanumab has restored its faith in the drug as a game-changer for Alzheimer’s and, after talking it over with the FDA, they’ll now be filing for an approval of a drug that had been given up for dead.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 63,000+ biopharma pros reading Endpoints daily — and it's free.

Vas Narasimhan. Getty Images

UP­DAT­ED: Failed PhI­II fe­vip­iprant tri­als pour more cold wa­ter on No­var­tis' block­buster R&D en­gine — and briefly spread the chill to a high-pro­file biotech

Back in July, during an investor call where Novartis execs ran through an upbeat assessment of their Q2 performance, CEO Vas Narasimhan and development chief John Tsai were pressed to predict which of the two looming Phase III readouts — involving cardio drug Entresto and asthma therapy fevipiprant, respectively — had a higher likelihood of success. Tsai gave the PARAGON-HF study with Entresto minimally better odds, but Narasimhan emphasized that their strategy of giving fevipiprant to more severe patients gave them confidence.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 63,000+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: The FDA sets a reg­u­la­to­ry speed record, pro­vid­ing a snap OK for Ver­tex's break­through triplet for cys­tic fi­bro­sis

The FDA has approved Vertex’s new triplet for cystic fibrosis at a record-setting speed.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 63,000+ biopharma pros reading Endpoints daily — and it's free.

IM­brave150: Roche’s reg­u­la­to­ry crew plans a glob­al roll­out of Tecen­triq com­bo for liv­er can­cer as PhI­II scores a hit

Just weeks after Bristol-Myers Squibb defended its failed pivotal study pitting Opdivo against Nexavar in liver cancer, Roche says it’s beat the frontline challenge with a combination of their PD-L1 Tecentriq with Avastin. And now they’re rolling their regulatory teams in the US, Europe and China in search of a new approval — badly needed to boost a trailing franchise effort.
Given their breakthrough and Big Pharma status as well as the use of two approved drugs, FDA approval may well prove to be something of a formality. And the Chinese have been clear that they want new drugs for liver cancer, where lethal disease rates are particularly high.
Researchers at their big biotech sub, Genentech, say that the combo beat Bayer’s Nexavar on both progression-free survival as well as overall survival — the first advance in this field in more than a decade. We won’t get the breakdown in months of life gained, but it’s a big win for Roche, which has lagged far, far behind Keytruda and Opdivo, the dominant PD-1s that have captured the bulk of the checkpoint market so far.
Researchers recruited hepatocellular carcinoma — the most common form of liver cancer — patients for the IMbrave150 study who weren’t eligible for surgery ahead of any systemic treatment of the disease.
Roche has a fairly low bar to beat, with modest survival benefit for Nexavar, approved for this indication 12 years ago. But they also plan to offer a combo therapy that could have significantly less toxicity, offering patients a much easier treatment regimen.
Cowen’s Steven Scala recently sized up the importance of IMbrave150, noting:

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 63,000+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: Clay Sie­gall’s $614M wa­ger on tu­ca­tinib pays off with solid­ly pos­i­tive piv­otal da­ta and a date with the FDA

Back at the beginning of 2018, Clay Siegall snagged a cancer drug called tucatinib with a $614 million cash deal to buy Cascadian. It paid off today with a solid set of mid-stage data for HER2 positive breast cancer that will in turn serve as the pivotal win Siegall needs to seek an accelerated approval in the push for a new triplet therapy.

And if all the cards keep falling in its favor, they’ll move from 1 drug on the market to 3 in 2020, which is shaping up as a landmark year as Seattle Genetics prepares for its 23rd anniversary on July 15.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 63,000+ biopharma pros reading Endpoints daily — and it's free.

David Liu, Liu Group

David Liu un­veils newest ad­vance­ment in CRISPR tech: Prime edit­ing

The researcher behind base-editing is out with what some scientists are hailing as the biggest advancement in CRISPR technology since that 2016 breakthrough: “prime editing.” The new molecular gadget is capable of erasing any base pair and stenciling in another and cutting or adding long segments of DNA without breaking both strands of the helix.

David Liu, base editing pioneer and founder of Beam Therapeutics, published the findings in Nature alongside Andrew Anzalone. They estimated that the breakthrough “in principle” puts 89% of human diseases in purview — although experts cautioned that human therapies were a long way off.

Bhaskar Chaudhuri. Frazier Healthcare Partners

Fra­zier Health­care Part­ner­s' der­ma­tol­ogy up­start at­tracts a mar­quee syn­di­cate, $94M+ for 'in-be­tween' top­i­cal drug

For the past three years Frazier Healthcare Partners’ Bhaskar Chaudhuri has been carefully and quietly grooming Arcutis Therapeutics, a new dermatology play he co-founded to deliver topical formulations of well-known drugs. Now that the biotech is poised to enter Phase III, he’s being joined by a marquee syndicate for its $94.5 million Series C.

HBM Healthcare Investments, Vivo Capital, BlackRock, Omega Funds, Pivotal BioVentures, and Goldman Sachs jumped on board, joining Bain Capital Life Sciences, OrbiMed and RA Capital Management in backing Arcutis’ lead topical cream for plaque psoriasis.

A new com­pa­ny en­ters the Tec­fidera fight, of­fer­ing to kill two birds

The remedy for the most common side effect for one of the most common multiple sclerosis drugs is simple: aspirin.

Taking aspirin with Biogen’s Tecfidera will reduce the flush, a sometimes painful form of red skin irritation, many patients experiences. The problem is that the aspirin has to be taken at least 30 minutes before Tecfidera, turning a simple twice-a-day, one-dose oral drug into a staggered two-drug regimen.

UP­DAT­ED: Bris­tol-My­ers makes Op­di­vo pitch for front­line lung can­cer with open la­bel PhI­II study

Despite a head start, when Bristol-Myers Squibb and its pioneering checkpoint inhibitor Opdivo suffered a key lung cancer setback in 2016, they found themselves relegated to the backseat as Merck’s Keytruda seized the wheel on the road to immunotherapy stardom. Bristol-Myers has since suffered blow after blow in its quest to take a big slice of the lucrative market, peppered with some small successes. On Tuesday, the New Jersey drugmaker touted positive data from a Phase III open-label study in a bid to carve itself a piece of the frontline lung cancer market.