Top FDA of­fi­cial ac­cused CDER chief Wood­cock of ap­pear­ing bi­ased, brow­beat­ing re­view­ers in de­mand­ing eteplirsen OK

While FDA com­mis­sion­er Rob Califf was try­ing to nav­i­gate an in­ter­nal civ­il war at the agency over its con­tro­ver­sial de­ci­sion to pro­vide an ac­cel­er­at­ed ap­proval for Sarep­ta’s eteplirsen, John Jenk­ins, then head of the Of­fice of New Drugs, sent him a memo which de­tailed a blis­ter­ing at­tack on CDER chief Janet Wood­cock.

Janet Wood­cock

It was Wood­cock who de­mand­ed, and won, the ar­gu­ment in fa­vor of an ac­cel­er­at­ed OK of the Duchenne mus­cu­lar dy­s­tro­phy drug.

But Jenk­ins, who sided with oth­er top of­fi­cials at the FDA in op­pos­ing the ap­proval, says that Wood­cock cre­at­ed an “ap­pear­ance of bias” in push­ing for the ap­proval from an ear­ly point. Wood­cock, he wrote Califf in a memo dat­ed Sep­tem­ber 14, 2016, left the FDA re­view team feel­ing pres­sured to come over to her side. And she by­passed the usu­al chain of com­mand to get what she want­ed, in­sist­ing on an ap­proval even be­fore the re­view team had com­plet­ed its task and leav­ing them dis­trust­ful of her role and man­ner.

Not on­ly did Jenk­ins ob­ject to Wood­cock’s han­dling of eteplirsen, a drug which had the vo­cal sup­port of the Duchenne com­mu­ni­ty, he al­so told Califf that he had de­layed his re­tire­ment specif­i­cal­ly be­cause Wood­cock in­tend­ed to take his place af­ter he left. And that is ex­act­ly what she did.

The memo was high­light­ed in a re­port by Charles Seife on Un­dark, an on­line site that al­so in­clud­ed a copy of the full let­ter. You can read the whole doc­u­ment here.

While Califf pub­lished much of the doc­u­men­ta­tion around the dis­pute, this par­tic­u­lar memo did not sur­face un­til Seife’s FOIA law­suit forced it out. And it in­cludes the re­mark­able sug­ges­tion that Califf should coun­sel the pow­er­ful CDER chief on her man­ner and her meth­ods.

Jenk­ins has since re­tired from the FDA, but he de­clined to talk to Seife, as did Wood­cock. But his memo de­serves care­ful at­ten­tion. One ex­cerpt:

John Jenk­ins

On page 4, you state “there is al­so abun­dant ev­i­dence that Dr. Wood­cock heard and read FDACDER0001 all the sci­en­tif­ic ev­i­dence…” This im­plies she took these ac­tions BE­FORE reach­ing a de­ci­sion on the ap­pli­ca­tion, which is clear­ly not cor­rect giv­en her state­ment to the re­view team of her in­ten­tion to over­rule them and ap­prove the drug BE­FORE they had com­plet­ed their re­views. Keep in mind this oc­curred af­ter an AC (ad­vi­so­ry com­mit­tee) meet­ing at which the ma­jor­i­ty of the pan­el vot­ed against both AA and full ap­proval. It is al­so clear that she was pre­pared to ap­prove the drug over the team’s ob­jec­tions by the orig­i­nal PDU­FA goal date and on­ly re­luc­tant­ly agreed to press the spon­sor for ad­di­tion­al da­ta on dy­s­trophin pro­duc­tion from the on­go­ing open-la­bel tri­al. While I am glad she agreed to go along with that re­quest, con­vinc­ing her to take what seemed like a very log­i­cal ac­tion was not easy. So, I find it hard to rec­on­cile your state­ments about the process with the ac­tions tak­en. Keep in mind that the usu­al course of ac­tion would be for the Of­fice to is­sue a CR let­ter and then the spon­sor could sub­mit a FDRR that would first come to me and on­ly if I sup­port­ed the Of­fice would an FDRR go to the Cen­ter Di­rec­tor. In this case that process was by­passed.

His memo goes on to out­line his con­cerns about the com­plete lack of da­ta on ef­fi­ca­cy as well as con­cerns that ac­cel­er­at­ed ap­proval would clear­ly low­er the bar at the agency on a new drug OK.

Al­so on page 9 it is iron­ic that you at­tribute to Janet the idea of ran­dom­iz­ing ear­ly in or­der to gen­er­ate good ev­i­dence. That is ex­act­ly what the re­view team planned to re­quire of Sarep­ta af­ter the re­sults of the 12-pa­tient study be­came avail­able, but it was Janet that pressed that a new ran­dom­ized tri­al not be re­quired. So, if Janet had fol­lowed the nor­mal CDER process in this case the re­view team would have re­quired place­bo-con­trolled tri­als, as they did for dris­apersen and we would have bet­ter da­ta on which to make a de­ci­sion.

Jenk­ins stops one step short of ac­cus­ing Wood­cock of bul­ly­ing the staff.

While I un­der­stand your de­sire not to un­der­cut her role as Cen­ter Di­rec­tor, her ac­tions have at best cre­at­ed a serous …ap­pear­ance of bias among the re­view team mem­bers and that has cre­at­ed dis­trust and a sense of un­due pres­sure to “come around” to her way of think­ing. Even if you up­hold her de­ci­sion I would think you should coun­sel her about how her be­hav­ior and ac­tions have un­der­mined her cred­i­bil­i­ty among the re­view staff and should be avoid­ed in fu­ture sim­i­lar cas­es. Ef­fec­tive lead­ers must have the trust and re­spect of their staff.

Lat­er, just be­fore he re­tired, Jenk­ins gave a speech in which he tried to warn oth­er drug de­vel­op­ers to avoid try­ing to fol­low the same path that Sarep­ta took. But he was clear­ly con­cerned about the fu­ture:

As you know, I had planned to re­tire from FDA last spring. I have de­layed my de­par­ture for a va­ri­ety of rea­sons, but one of the most im­por­tant rea­sons is that Janet has told me she plans to serve as act­ing in my place as head of OND once I leave. I am very con­cerned about the im­pact of that de­ci­sion on the fu­ture of the new drugs re­view pro­gram and would be hap­py to dis­cuss those con­cerns fur­ther.

UP­DAT­ED: Roche bags 'break­through' an­ti-fi­bro­sis drug in $1.4B biotech buy­out deal

Roche is snapping up a “breakthrough” anti-fibrotic drug in a $1.4 billion buyout.

The pharma giant announced Friday that it is acquiring Promedior, primarily to get its hands on PRM-151, a recombinant form of human pentraxin-2 (PTX-2) protein that has nailed down mid-stage clinical data on idiopathic pulmonary fibrosis and demonstrating its potential for a range of fibrotic conditions.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,700+ biopharma pros reading Endpoints daily — and it's free.

(Image: Associated Press)

Amarin emerges from an ex­pert pan­el re­view with a clear en­dorse­ment for Vas­cepa and high odds of suc­cess when the FDA weighs in for­mal­ly

Several FDA experts who gathered Thursday to consider the landmark approval of Vascepa to reduce cardio events in an at-risk population voiced their unease about various aspects of the efficacy and safety data, or ultimately the population it should be used to treat. But the overwhelming belief that the data pointed to the drug’s benefit and clearly outweighed risks carried the day for Amarin.

The panel voted unanimously (16 to 0) to support the company’s positive data presentation — backing an OK for expanding the label to include reducing cardio risk. The vote points Amarin $AMRN down a short path to a formal decision by the FDA, with the odds heavily in its favor. Chances are the rest of the questions about the future of this drug will be hashed out in the label’s small print.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,700+ biopharma pros reading Endpoints daily — and it's free.

Federal Trade Commission commissioner Rohit Chopra testifies on Capitol Hill (AP Photo/Susan Walsh)

FTC clears Bris­tol-My­ers’ $74B deal to buy Cel­gene — but Dems sig­nal a po­ten­tial hard shift against Big Phar­ma M&A

Bristol-Myers Squibb’s record $74 billion takeover of Celgene is a done deal. And it will all be over — except for the lingering complaints from die-hard Celgene investors — on Wednesday.

Like much else that’s going on in Washington these days, the vote among the 5 FTC commissioners split along party lines, with the 3 Republicans voting to clear the way and the 2 Democrats steamed over what they see as a major M&A move that will lessen competition and innovation. And that split has big implications for the M&A side of the business if the Dems take the White House in 2020.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,700+ biopharma pros reading Endpoints daily — and it's free.

No­var­tis spin­out’s first an­ti-ag­ing PhI­II is a flop, so now they’ll turn to Parkin­son’s chal­lenge as shares wilt

Novartis spinout resTORbio is grappling with the collapse of its lead clinical program this morning — an anti-aging R&D failure that will badly damage their rep in the field.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,700+ biopharma pros reading Endpoints daily — and it's free.

BeiGene CEO John Oyler at an Endpoints event in Shanghai, October 2018 (Credit: Endpoints News/PharmCube)

UP­DAT­ED: In a first, FDA green-lights use of a Chi­nese built can­cer ther­a­py — and more are com­ing

Weeks after Amgen took a $2.7 billion stake in BeiGene, the Beijing-based biotech has secured its first-ever FDA approval for zanubrutinib, a BTK inhibitor, months ahead of schedule.

BeiGene’s drug, branded as Brukinsa, has secured accelerated approval for adult patients with mantle cell lymphoma (MCL) — a typically aggressive, rare, form of blood cancer — who have received at least one prior therapy.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,700+ biopharma pros reading Endpoints daily — and it's free.

What does $62B buy you these days? A lot, says Take­da ex­ecs as the phar­ma play­er promis­es a block­buster R&D fu­ture

First comes the $62 billion buyout. Then comes the asset auction and reorganization to pay down debt. Now comes the detailed pledge of a bigger, brighter future in drug development.

That’s where Takeda finds itself on R&D day today, about 11 months after closing on their Shire acquisition. R&D chief Andy Plump is joining CEO Christophe Weber and other top members of the team to outline a new set of priorities in the greatly expanded pipeline at Takeda, which has jumped into the top ranks of the world’s pharma giants in the wake of the Shire deal.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,700+ biopharma pros reading Endpoints daily — and it's free.

GSK's asth­ma bi­o­log­ic Nu­cala scores in rare blood dis­or­der study

GlaxoSmithKline’s asthma drug Nucala, which received a resounding FDA rejection for use in chronic obstructive pulmonary disease (COPD) last year, has shown promise in a rare blood disorder.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,700+ biopharma pros reading Endpoints daily — and it's free.

Mer­ck buys a fledg­ling neu­rode­gen­er­a­tive biotech spawned by an old GSK dis­cov­ery al­liance. What’s up with that?

Avalon Ventures chief Jay Lichter has a well-known yen for drug development programs picked up in academia. And what he found in Haoxing Xu’s lab at the University of Michigan pricked his interest enough to launch one of his umbrella biotechs in San Diego.

Xu’s work laid the foundation for Avalon to launch Calporta, which has been working on finding small molecule agonists of TRPML1 (transient receptor potential cation channel, mucolipin subfamily, member 1) for lysosomal storage disorders. And that pathway, they believe, points to new approaches on major market neurodegenerative diseases like Parkinson’s, ALS and Alzheimer’s.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,700+ biopharma pros reading Endpoints daily — and it's free.

(Image: Associated Press)

No­var­tis scores its lat­est FDA OK — this time for a new sick­le cell dis­ease drug picked up in a $665M deal

Novartis’ decision to buy Oklahoma-based biotech Selexys 3 years ago for up to $665 million has paid off with an FDA approval today.

Blessed with the FDA’s breakthrough drug designation for a speedy review, the pharma giant has pinned down an approval for crizanlizumab, a new therapy designed to reduce the frequency of painful incidents of vaso-occlusive crises among sickle cell disease patients 16 or older.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 65,700+ biopharma pros reading Endpoints daily — and it's free.