WATCH: Scott Got­tlieb vows to shake up the FDA, back­ing a trend to­ward faster drug de­vel­op­ment

FDA com­mis­sion­er Scott Got­tlieb has sound­ed a crys­tal clear warn­ing over the high — and grow­ing — cost of drug de­vel­op­ment. And in a speech to reg­u­la­to­ry ex­ecs on Mon­day, Got­tlieb com­mit­ted the FDA to back­ing up more ef­fi­cient drug de­vel­op­ment pro­grams with new mea­sures to clear the reg­u­la­to­ry path for de­vel­op­ers bar­rel­ing ahead to rel­a­tive­ly swift piv­otal da­ta in search of an ac­cel­er­at­ed OK.

Got­tlieb start­ed by out­lin­ing a bleak pic­ture in drug R&D, not­ing that the eco­nom­ic mod­el for drug de­vel­op­ment is bro­ken. It costs too much to de­vel­op a drug so it can be ap­proved for mar­ket­ing. And costs are swelling fast at the dis­cov­ery end of the busi­ness, which will help swamp a sys­tem that al­ready doesn’t work par­tic­u­lar­ly well.

As he has in the past, Got­tlieb held up some of the rapid-fire clin­i­cal tri­als we’ve been see­ing in the can­cer field as a mod­el for what can work, paving the way to the ac­cel­er­at­ed ap­proval path­way at the FDA. And he be­lieves — though there is pre­cious lit­tle ev­i­dence to back it up — that mov­ing drug de­vel­op­ment in­to the fast lane can re­duce R&D costs and there­by al­low bio­phar­ma com­pa­nies to pass on sav­ings to pa­tients through low­er costs.

To help de­vel­op­ers, Got­tlieb vowed that the FDA, through CDER chief Janet Wood­cock and the Of­fice of New Drugs, will adapt the reg­u­la­to­ry path­way to en­able drug de­vel­op­ment at a more mod­er­ate cost.

Said Got­tlieb:

Com­pa­ra­ble reg­u­la­to­ry mile­stones need to be built in­to the new seam­less clin­i­cal tri­al process. We need to en­sure we pro­vide com­pa­ra­ble in­ter­ac­tions and over­sight.

He al­so not­ed that as de­vel­op­ers move to­ward faster, seam­less stud­ies — drop­ping the tra­di­tion­al Phase I through Phase III de­vel­op­ment plan — reg­u­la­tors al­so need to up­date pa­tients’ aware­ness of the risks in­volved in pro­vid­ing their con­sent for par­tic­i­pat­ing in these stud­ies.


Watch Got­tlieb’s speech and Q&A

Cred­it: RAPS


Here are some ex­cerpts from the speech, start­ing with an out­line of the trend to­ward a sin­gle de­vel­op­ment pro­gram for new drugs.

Ow­ing in part to these lead­er­ship ef­forts, we’ve seen more spon­sors de­vel­op on­col­o­gy drugs that for­go the con­ven­tion­al three se­quen­tial phas­es of drug de­vel­op­ment. They opt in­stead for seam­less ap­proach­es. Un­der these tri­al de­signs, they’ll typ­i­cal­ly add co­horts to a first-in-hu­man tri­al to in­ves­ti­gate dos­es and ac­tiv­i­ty in a va­ri­ety of can­cers.

We’ve seen ex­am­ples where this ap­proach has al­lowed the rapid de­vel­op­ment of drugs in mul­ti­ple dif­fer­ent tu­mor types. If we had to stop and start for­mal Phase II tri­als in each dif­fer­ent or­gan sys­tem where a can­cer arose, it could have been a pro­tract­ed process. This ap­proach is well suit­ed to the kinds of drugs that are be­ing de­vel­oped now, where drugs in­ter­vene on com­mon el­e­ments found across mul­ti­ple kinds of dis­ease states. At FDA, we’ve iden­ti­fied more than 40 ac­tive com­mer­cial in­ves­ti­ga­tion­al new drug ap­pli­ca­tions for large first-in-hu­man on­col­o­gy tri­als alone that use these seam­less strate­gies.

Got­tlieb al­so talked about us­ing broad pro­to­cols that al­low de­vel­op­ers to tack­le mul­ti­ple tar­gets at once.

We’re al­so ad­vanc­ing the use of ‘Mas­ter Pro­to­cols’ to en­able more co­or­di­nat­ed ways to use the same tri­al struc­ture to eval­u­ate treat­ments in more than one sub­type of a dis­ease or type of pa­tient.

This ap­proach is par­tic­u­lar­ly rel­e­vant when it comes to tar­get­ed drugs. These are drugs that may in­ter­vene on mark­ers that are rel­e­vant across many dif­fer­ent dis­ease sub­types. We may, for ex­am­ple, want to eval­u­ate these dif­fer­ent tar­gets si­mul­ta­ne­ous­ly, as part of one large study. This could give us a bet­ter way to un­der­stand the com­par­a­tive ben­e­fits of a drug across dif­fer­ent set­tings. To en­able these mas­ter pro­to­cols, it’s of­ten im­por­tant to do mol­e­c­u­lar pa­tient screen­ing. This can lead to the de­vel­op­ment of a di­ag­nos­tic that can al­so be used to guide pa­tient care.

Got­tlieb out­lined plans to in­vest more of the FDA’s mon­ey in new tech­nol­o­gy that can as­sist this faster/bet­ter/cheap­er ap­proach to drug de­vel­op­ment.

On the sec­ond point that I want­ed to high­light to­day, we’re al­so tak­ing new steps to mod­ern­ize how spon­sors can eval­u­ate clin­i­cal in­for­ma­tion, and how FDA re­views this da­ta as part of our reg­u­la­to­ry process.

This starts with bet­ter use of more ad­vanced com­put­ing tools, and more so­phis­ti­cat­ed sta­tis­ti­cal and com­pu­ta­tion­al method­olo­gies, as part of the drug de­vel­op­ment and the drug re­view process. This in­cludes more wide­spread use of mod­el­ing and sim­u­la­tion, and high per­for­mance com­put­ing clus­ters in­side FDA.

FDA al­ready has high per­for­mance com­put­ing clus­ters. These tools help us de­vel­op more so­phis­ti­cat­ed meth­ods for eval­u­at­ing the da­ta that’s sub­mit­ted to us from clin­i­cal tri­als. The com­put­ing tools al­so en­able us to prop­er­ly eval­u­ate the more so­phis­ti­cat­ed com­po­nents that are sub­mit­ted to us as part of prod­uct re­view ap­pli­ca­tions.

Got­tlieb al­so talked about shak­ing up the R&D ap­proach to some spe­cif­ic dis­eases that have proved par­tic­u­lar­ly hard to deal with.

Ad­di­tion­al­ly, to bet­ter de­lin­eate how we’re go­ing to ap­proach the over­all de­vel­op­ment and eval­u­a­tion of drugs tar­get­ed to cer­tain un­met med­ical needs, we plan to be­gin work on at least ten new dis­ease-spe­cif­ic guid­ance doc­u­ments over the next year. Some of these doc­u­ments are al­ready un­der­way. Among the dis­eases we’re tar­get­ing are ar­eas of sig­nif­i­cant un­met need like Amy­otroph­ic Lat­er­al Scle­ro­sis (ALS).

Re­vamp­ing the eco­nom­ics of drug R&D is no sim­ple task.

The on­col­o­gy field has been able to move far­ther and faster than oth­er dis­ease fields due to its abil­i­ty to test new drugs on pa­tients with ad­vanced dis­ease and dwin­dling hope of sur­vival. So it won’t be easy to trans­late that same ap­proach to mass mar­ket dis­eases like di­a­betes and car­dio, where mil­lions are treat­ed for years for chron­ic dis­ease.

An­oth­er big ques­tion is whether bio­phar­ma com­pa­nies will ac­tu­al­ly pass along any sav­ings they get from a more ef­fi­cient de­vel­op­ment path­way to pay­ers and con­sumers. The en­tire in­dus­try has been tip­ping more and more of its de­vel­op­ment dol­lars to can­cer in part be­cause of the big re­wards that come from fast ap­provals. And the FDA has no con­trol what­so­ev­er over the fi­nal price drug de­vel­op­ers use for their new drugs.

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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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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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