Dear Pres­i­dent Trump: Don’t de­stroy the FDA we know and re­spect

On Tues­day, a group of Big Phar­ma ex­ecs from Mer­ck, J&J, Am­gen, Eli Lil­ly and Cel­gene gath­ered to pay court to Pres­i­dent Don­ald Trump at the White House. Trump didn’t dis­ap­point ei­ther his ad­mir­ers or his crit­ics, launch­ing in­to a full throat­ed ha­rangue on high drug prices while vow­ing to the col­lec­tion of CEOs that he was about to erase a large num­ber of the reg­u­la­tions on drug de­vel­op­ment to speed the ar­rival of a new gen­er­a­tion of drugs at a low­er cost.

He promised a rev­o­lu­tion at the FDA.

“We’re go­ing to be cut­ting reg­u­la­tions at a lev­el peo­ple have nev­er seen be­fore,” Trump said. Peo­ple can still be pro­tect­ed, he said, “but in­stead of 9,000 pages it can be 100 pages. And you don’t have to dou­ble up and quadru­ple up. We have com­pa­nies that have more peo­ple work­ing on reg­u­la­tions than they have work­ing at the com­pa­ny.”

The CEOs in at­ten­dance nod­ded in com­pli­ance, voic­ing their sup­port for the move — while like­ly be­ing par­tic­u­lar­ly keen on tax re­form that would boost prof­its and al­low them to repa­tri­ate bil­lions in cash.

But his com­ments didn’t play so well with biotech ex­ecs. I asked for some feed­back from drug de­vel­op­ers I know, and the re­sponse was an un­equiv­o­cal ‘no thanks.’

From their per­spec­tive, the FDA has al­ready made ma­jor changes that al­low for faster drug de­vel­op­ment. If Trump is talk­ing about shred­ding agency stan­dards and green-light­ing fast-and-dirty ap­provals for drugs with no clear proof of ef­fi­ca­cy and safe­ty, he’s threat­en­ing every de­vel­op­er with in­tegri­ty.

In Trump’s brave new world, pay­ers will be prompt­ed to throw up even high­er walls against new drugs with scant da­ta back­ing them up.

But here’s what they had to say, in their own words.


Michael Gilman, se­r­i­al biotech en­tre­pre­neur:

I will try not to de­volve to a full-on rant here, but in my view it’s nuts to as­cribe a ma­te­r­i­al por­tion of the time and cost of drug de­vel­op­ment to FDA “reg­u­la­tions.” Yes, there are plen­ty of those, but they are large­ly in the ser­vice of pro­tect­ing the safe­ty of pa­tients and clin­i­cal tri­al sub­jects. What makes drug de­vel­op­ment long and ex­pen­sive is the need to prove, be­yond sta­tis­ti­cal doubt, that your damn drug works. That’s not on the FDA — that’s on the un­der­ly­ing bi­ol­o­gy of the dis­eases we’re try­ing to crack. Low­er­ing the bar for proof is invit­ing both cat­a­stro­phe for pa­tients and even more wast­ed mon­ey in a sys­tem that is forced to pay for drugs that don’t work — and may even in­flict harm.

Crazy shit every­where you turn.


John Maraganore, CEO Al­ny­lam:

We need to main­tain stan­dards for both safe­ty AND ef­fi­ca­cy, and work with the FDA to iden­ti­fy nov­el path­ways and clin­i­cal tri­al de­signs that can speed in­no­v­a­tive med­i­cines to pa­tients. We’ve been do­ing this with FDA over the last decade with FDA­SIA, 21st Cen­tu­ry Cures, and PDU­FA VI. This will con­tin­ue in the fu­ture as we learn how to in­te­grate the pa­tient voice, re­al world ev­i­dence, and “big da­ta” in­to the drug de­vel­op­ment process. But the bot­tom line is that pa­tients and physi­cians need to know that the med­i­cines they take are safe AND ef­fec­tive. And these days, pay­ers al­so need to have ev­i­dence for a drug’s ef­fi­ca­cy and val­ue for re­im­burse­ment.


Steve Holtz­man, CEO, Deci­bel:

Most (at least the good ones) biotech ex­ec­u­tives val­ue a strong, sci­ence-based FDA; hence, I don’t think you will see any sup­port for cuts in FDA reg­u­la­tion.  Most of the CEO’s I know were pret­ty ap­palled by the Sarep­ta ap­proval as, giv­en the da­ta, it seemed to be ap­proval of a very ex­pen­sive, safe place­bo that rais­es pa­tients’ hope in­ap­pro­pri­ate­ly.  Is there some red tape to­day? Sure.  Is it out­weighed by the vi­tal func­tion played by the Agency to safe­guard the health and well-be­ing of the pop­u­lace?  You bet.

Cut­ting FDA staffing dras­ti­cal­ly would be prob­lem­at­ic as it will slow down the (thor­ough) re­view of po­ten­tial­ly im­por­tant new med­i­cines.  I stress the word “thor­ough” in the fore­go­ing sen­tence.  If the Ad­min­is­tra­tion cuts staffing, and then turns up the pres­sure to ap­prove drugs more quick­ly, that will be tan­ta­mount to a com­pro­mise of the sci­en­tif­ic na­ture of the reg­u­la­tion.  It will drift to­ward the stat­ed goal of some in the Ad­min­is­tra­tion to lim­it­ing re­views to mat­ters of safe­ty while leav­ing to the mar­ket the eval­u­a­tion of ef­fi­ca­cy.  Again, most biotech ex­ecs do not fa­vor this ap­proach (see Sarep­ta, above).  Al­so, Right to Try, is not sup­port­ed by the in­dus­try.  It pos­es a threat to con­duct­ing well con­trolled reg­is­tra­tional tri­als.


Bassil Dahiy­at, CEO of Xen­cor:

Steve said it beau­ti­ful­ly and I agree com­plete­ly.  I’d ar­gue that a strong, sci­ence-based FDA helped cre­ate the biotech­nol­o­gy in­dus­try by cre­at­ing a way for doc­tors, and fi­nan­cial mar­kets, to know if a med­i­cine ac­tu­al­ly worked (ef­fi­ca­cy too!) and was worth try­ing or in­vest­ing in.  And now for pay­ers to know if it is worth pay­ing for.  In­di­vid­ual doc­tors and pa­tients will have no way of de­duc­ing from the mi­cro­cosm of their own ex­pe­ri­ence how a new drug im­pacts a dis­ease; very very few sit­u­a­tions are as eas­i­ly in­ter­pret­ed as “you take an an­tibi­ot­ic and your ear in­fec­tion goes away in a cou­ple days.” And we don’t want to mar­ket things that don’t work.

The FDA seems very en­gaged with all of the new ini­tia­tives that are be­ing tried to­day.  Want to help biotech in­no­va­tion, small com­pa­nies and cre­ate more new med­i­cines by re­duc­ing reg­u­la­to­ry bur­dens?  Fund the agency more, hire more re­view­ers and let the FDA pay high­ly skilled sci­ence and med­ical re­view­ers com­pet­i­tive­ly to the mar­kets for their la­bor.


Je­re­my Levin, CEO, Ovid:

I would on­ly add:

First­ly, that over the last sev­er­al years there has been mas­sive changes in the per­for­mance of the FDA and the re­la­tion­ship with them has dra­mat­i­cal­ly im­proved.  They are the part­ners to our in­dus­try and be­have as such to in­sure the safe­ty AND the ef­fi­ca­cy of de­vices and med­i­cines.  In part the rea­son why Amer­i­ca has lead­er­ship in de­vel­op­ing med­i­cines is not just that we have great sci­en­tists, clin­i­cians, fi­nanc­ing and an in­fra­struc­ture to sup­port and en­cour­age in­no­va­tion, it is al­so be­cause we have the best reg­u­la­to­ry process in the world.  Work­ing with it we will move in­creas­ing­ly to es­tab­lish how to lay the foun­da­tion for what val­ue a drug brings.

Sec­ond­ly, with­out rig­or­ous sci­en­tif­ic and med­ical proof to es­tab­lish that a drug is both Safe and Ef­fec­tive, we risk tak­ing a step back in­to a time when peo­ple sold col­ored wa­ter for can­cer treat­ments and pa­tients be­came the un­wit­ting tools of un­scrupu­lous mar­ke­teers.  Pro­pos­als that walk us back to that time, are counter to in­no­va­tion and lead­er­ship in the world of med­i­cine.  They are not just bad for sci­ence and clin­i­cal med­i­cine and dan­ger­ous to pa­tients, they risk be­ing un­eth­i­cal and bad for busi­ness and the in­dus­try.


Ron Co­hen, CEO of Acor­da:

I would add on­ly that there as in­deed been im­mense progress in FDA ef­fi­cien­cy and ap­provals of new med­i­cines over the past 5 years, and we ex­pect fur­ther progress to be made based on such leg­is­la­tion as the bi­par­ti­san 21st Cen­tu­ry Cures Act. There is al­so a clear move now to­ward re­im­burse­ment for med­i­cines based on out­comes and the val­ue that these out­comes rep­re­sent, which the in­dus­try sup­ports and would like to see fur­ther en­abled by ju­di­cious re­lax­ing of cer­tain reg­u­la­tions that in­hib­it such agree­ments be­tween bio­phar­ma and pay­ers.  In ad­di­tion to the is­sues raised by the oth­ers on this thread, low­er­ing the stan­dards for de­ter­min­ing safe­ty and ef­fi­ca­cy will lead to enor­mous chal­lenges in get­ting drugs re­im­bursed, as pay­ers will have  less da­ta on which to base de­ter­mi­na­tions of out­comes and val­ue. Pa­tients there­fore will be at risk of hav­ing less ac­cess to need­ed med­i­cines.


Bernard Munos

Bernard Munos, Founder of In­no­Think Cen­ter for Re­search in Bio­med­ical In­no­va­tion:

I am afraid that this talk of FDA dereg­u­la­tion is an­oth­er as­sault of ide­ol­o­gy over ev­i­dence. The re­search (done by Hen­ry Grabows­ki and his team at Duke many years ago) is clear: in­no­va­tion is best served by ex­act­ing reg­u­la­to­ry stan­dards. Coun­tries with the high­est stan­dards (US, UK) have fos­tered the most com­pet­i­tive and in­no­v­a­tive bio­phar­ma com­pa­nies. When they ap­prove drugs, they of­ten be­come glob­al brands that dom­i­nate their ther­a­peu­tic cat­e­gories be­cause they are su­pe­ri­or. In con­trast, coun­tries with per­mis­sive regimes (France, Japan) ap­prove more drugs – Trump’s goal – that may get trac­tion in their do­mes­tic mar­kets, but sel­dom sell much out­side be­cause they are mediocre (save for the oc­ca­sion­al ex­cep­tions). In­no­va­tors know that in their guts, and have spo­ken out loud­ly against plans to de­base FDA (e.g., Len Schleifer). Any­one can come up with safe snake oil, but, if that be­comes our reg­u­la­to­ry stan­dard, that’s what we’re go­ing to get. Will it cre­ate a vi­brant in­dus­try? No, it will oblit­er­ate it.

If the pres­i­dent wants to cut costs and speed drug to mar­kets – laud­able goals – cut­ting cor­ners on safe­ty and/or ef­fi­ca­cy stud­ies is not the way to do it. In­stead, he should look at cheap­er/faster ways the col­lect the da­ta need­ed to demon­strate safe­ty/ef­fi­ca­cy. As it hap­pens, new tech­nolo­gies are emerg­ing that do just that (e.g., biosen­sors, apps), and the US has a lead in them. C And FDA has al­so been quick to em­brace them and ap­prove clin­i­cal tri­als that use them. If any­thing, it is the con­ser­v­a­tive phar­ma com­pa­nies which have been drag­ging their feet (or more pre­cise­ly the com­pli­ance and reg­u­la­to­ry groups in these com­pa­nies, which are loath to use “un­proven” reg­u­la­to­ry path­ways.) There is al­so usu­al­ly enough mon­ey to keep do­ing things the tra­di­tion­al way, so why take a “risk”? If the pres­i­dent wants to help, he could prod the in­dus­try to get on with tech­nol­o­gy that can sig­nif­i­cant­ly cut costs. It spends over $100 bil­lion a year in col­lect­ing clin­i­cal da­ta in hos­pi­tals, slow­ly, in the old-fash­ioned way. Any dent we can make in that spend­ing could be quite mean­ing­ful.

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.

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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.

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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:

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That $335M JV Bay­er set up on CRISPR/Cas9? They’re let­ting the biotech part­ner car­ry on

Bayer committed $300 million to set up a joint venture on CRISPR/Cas9 tech with CRISPR Therapeutics $CRSP. But they’re handing off control now to the smaller biotech while retaining a couple of opt-ins for programs nearing an IND.

Bayer $BAY made much of the fact that they were going all-in on gene editing when they did their deal 3 years ago with CRISPR Therapeutics, which pitched $35 million in on their end. This was the cornerstone of their plan to set up new JVs that could make some serious leap forwards in hot new R&D spaces. Now CRISPR will have full management control of Casebia as they pursue programs in hemophilia, ophthalmology and autoimmune diseases.
Samarth Kulkarni, the CEO at CRISPR, made it sound like a natural progression.

J&J's block­buster Ste­lara wins US ap­proval for ul­cer­a­tive col­i­tis

J&J’s Stelara, which is set to be in the top ten list of blockbusters come 2025, is now cleared by the FDA for use in ulcerative colitis (UC), an inflammatory disease of the large intestine.

The biologic targets interleukin (IL)-12 and IL-23 cytokines, which are known to play a key role in inflammatory and immune responses. Stelara, which generated about $4.7 billion in the first nine months of 2019, is a key player in the crowded marketplace of drugs to treat autoimmune disorders such as psoriasis, rheumatoid arthritis and Crohn’s disease. AbbVie’s star therapy, Humira, continues to dominate, despite its looming patent cliff in the United States, while others including J&J’s $JNJ own anti-IL23 Tremfya, Lilly’s $LLY anti-IL-17 Taltz and AbbVie’s $ABBV recently approved anti-IL-23 antibody Skyrizi carve out a slice of market share.

Drug com­pa­nies reach $260M set­tle­ment just ahead of opi­oid tri­al; Oys­ter Point set terms for $85M IPO

→ Hours before the first federal opioid trial was set to begin, three drug distributors and an opioid manufacturer agreed to a $260 million agreement settlement, the Wall Street Journal was the first to report. The deal — which will see McKesson, Cardinal Health and AmerisourceBergen pay $215 million to Summit and Cuyahoga counties, and Teva deal out $35 million in cash and addiction treatments — does not resolve the pending, nationwide litigation that may result in a settlement worth upwards of $40 billion. Negotiators in that case, brought by 2,300 tribes, counties and cities nationwide and led by several states’ attorneys general, worked through much of Friday without success. Josh Stein, the attorney general for North Carolina, said they were trying to put together a $48 billion deal.

GSK of­floads two vac­cines in $1.1B deal as it works to re­vive the pipeline

GlaxoSmithKline is leaving the deep dark woods and its viruses behind.

GSK has agreed to divest its vaccines for rabies, RabAvert, and tick-born encephalitis vaccine, Encepur, to Bavarian Nordic, part of the company’s broader efforts to narrow its pipeline and focus on oncology and immunology.

The deal is worth up to nearly $1.1 billion, with a $336 million upfront payment. GSK acquired the vaccines from Novartis as part of an exchange for their late-stage oncology programs in 2015 under former chief Sir Andrew Witty.

Pfiz­er gets some en­cour­ag­ing PhI­II news on a fran­chise sav­ior, but is a dos­ing ad­van­tage worth the $295M up­front?

Close to 3 years after Opko tried to defend itself as shares tumbled on the news that its long-acting growth hormone had failed to outperform a placebo, the Pfizer partner $PFE is back. And this time they’re pitching Phase III data that demonstrate their drug is non-inferior — or maybe a tad better — than their well-known but fading standard in the field.
The comparator drug here is Genotropin, which earned a marginal $142 million for Pfizer last year — down 9% from the year before. Approved 24 years ago, biosimilars are now in development that Pfizer would like to stay out in front of. The market leader here is Norditropin, a growth hormone from Novo Nordisk that uses the same basic ingredient as Genotropin, which the Danish company sells with a kid-friendly self-injectable pen. That would also present some big competition if the new therapy from Opko/Pfizer makes it to the market.
The new data, says researchers, underscore that a weekly injection of somatrogon performed as well or slightly better than Genotropin (somatropin) in young children with growth hormone deficiency. Investigators tracked height velocity at 10.12 cm/year, edging out the older drug’s 9.78 cm/year. That 0.33 difference may not prove compelling to payers, though, who have been known to overlook dosing advantages in favor of lower costs.
That message may have weighed on the stock reaction this morning, with a 30%-plus hike $OPK giving way to more marginal gains.
Back in late 2016, Opko had to defend itself against a devastating Phase III setback as their initial late-stage trial failed against a sugar pill. Opko later blamed that setback on outliers in the study, though it wasn’t able to expunge the failure.

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As­traZeneca's Farx­i­ga scores FDA nod to cut risk of hos­pi­tal­iza­tion for heart fail­ure in di­a­bet­ics

While the FDA recently spurned an application to allow AstraZeneca’s blockbuster drug Farxiga for type 1 diabetes that cannot be controlled by insulin, citing safety concerns — the US regulator has endorsed the use of the SGLT2 treatment to reduce the risk of hospitalisation for heart failure in patients with type-2 diabetes and established cardiovascular disease or multiple CV risk factors.