Got­tlieb lays out re­al world ev­i­dence pri­or­i­ties for 2019 with an eye on dig­i­tal tools

Stress­ing the need for speed and ef­fi­cien­cy, FDA Com­mis­sion­er Scott Got­tlieb on Mon­day of­fered a look at FDA’s plans around re­al-world da­ta (RWD) and re­al-world ev­i­dence (RWE) in 2019.

The speech at the Bi­par­ti­san Pol­i­cy Cen­ter built off a frame­work, re­leased in De­cem­ber, that sought to be­gin the con­ver­sa­tion on how RWD and RWE can sup­port changes to la­bel­ing, in­clud­ing adding or mod­i­fy­ing an in­di­ca­tion, changes in dose, dose reg­i­men or route of ad­min­is­tra­tion; chang­ing or adding new pop­u­la­tions; or the ad­di­tion of com­par­a­tive ef­fec­tive­ness or safe­ty in­for­ma­tion.

“Tra­di­tion­al post­mar­ket stud­ies typ­i­cal­ly re­quire years to de­sign and com­plete and cost mil­lions of dol­lars. By us­ing RWD and RWE, we may be able to pro­vide pa­tients and providers with im­por­tant an­swers much soon­er – iden­ti­fy­ing a broad­er range of safe­ty sig­nals more quick­ly, and fol­low­ing up on them much more ef­fec­tive­ly,” Got­tlieb said, not­ing this is es­pe­cial­ly im­por­tant for treat­ments for un­com­mon con­di­tions, such as rare tu­mor types.

Got­tlieb al­so laid out four ad­di­tion­al ac­tiv­i­ties the FDA is tak­ing in con­nec­tion to RWE and RWD this year.

First, to sup­port the in­te­gra­tion of dig­i­tal tech­nolo­gies in clin­i­cal tri­als, the FDA is plan­ning to con­vene a stake­hold­er meet­ing to help de­vel­op a frame­work on how dig­i­tal sys­tems can be used to en­hance the over­sight of clin­i­cal tri­als.

“To take one ex­am­ple, re­mote- and risk-based mon­i­tor­ing can pro­vide bet­ter reg­u­la­to­ry over­sight,” he said. “These ap­proach­es may low­er de­vel­op­ment costs, and en­able more tri­al sites to an­swer im­por­tant sci­en­tif­ic and clin­i­cal ques­tions as a way to im­prove pa­tient care.”

He al­so said the FDA will use dig­i­tal tech­nolo­gies to bring clin­i­cal tri­als to the pa­tient, rather than al­ways re­quir­ing the pa­tient to trav­el to the in­ves­ti­ga­tor.

“To sup­port the de­vel­op­ment and adop­tion of de­cen­tral­ized tri­als, the FDA es­tab­lished a for­mal work­ing group on de­cen­tral­ized tri­als, and we’re work­ing to­wards writ­ing a guid­ance doc­u­ment to out­line our ap­proach. We’ll
have much more to say about this in the next month,” he said.

And third, the FDA is ex­plor­ing how re­view­ers can gain more in­sight in­to how la­bel­ing changes in­form provider pre­scrib­ing de­ci­sions and pa­tient out­comes. The FDA’s In­for­ma­tion Ex­change and Da­ta Trans­for­ma­tion (IN­FORMED) is us­ing RWD to ex­am­ine the im­pact of a re­cent FDA la­bel­ing change for two ap­proved prod­ucts from weight-based dos­ing to flat-dos­ing of im­mune check­point in­hibitors.

In 2019, IN­FORMED is go­ing to be work­ing with FDA’s med­ical prod­uct cen­ters to de­vel­op an FDA cur­ricu­lum on ma­chine learn­ing and ar­ti­fi­cial in­tel­li­gence in part­ner­ship with ex­ter­nal aca­d­e­m­ic part­ners.

“The agency will al­so pi­lot a com­pet­i­tive fel­low­ship pro­gram un­der IN­FORMED in ar­ti­fi­cial in­tel­li­gence and ma­chine learn­ing that al­lows post-doc­tor­al fel­lows from lead­ing aca­d­e­m­ic cen­ters to join the FDA for two-year fel­low­ships to de­vel­op high-im­pact AI-based reg­u­la­to­ry sci­ence tools by work­ing close­ly with men­tors from the agency’s med­ical prod­uct cen­ters,” Got­tlieb said.

He al­so not­ed that in on­col­o­gy, the FDA cur­rent­ly has new drug ap­pli­ca­tions un­der re­view where RWD and RWE are help­ing to in­form on­go­ing eval­u­a­tions.

The FDA’s On­col­o­gy Cen­ter of Ex­cel­lence (OCE) is work­ing with Friends of Can­cer Re­search, the Na­tion­al Can­cer In­sti­tute and oth­er stake­hold­ers to har­mo­nize ref­er­ence stan­dards for as­sess­ing tu­mor mu­ta­tion­al bur­den to help iden­ti­fy can­cer pa­tients who are more like­ly to re­spond to im­munother­a­py.

“OCE is al­so work­ing on a project ex­plor­ing whether it’s pos­si­ble to use re­al world end­points, like time to treat­ment dis­con­tin­u­a­tion (TTD) from in lega­cy datasets as a po­ten­tial re­al-world end­point for prag­mat­ic ran­dom­ized clin­i­cal tri­als for FDA-ap­proved ther­a­pies in the off-la­bel set­ting, and whether syn­thet­ic con­trol arms based on pri­or clin­i­cal tri­als can be used for tu­mor types where the stan­dard of care has not changed in decades, and the prog­no­sis is es­pe­cial­ly poor,” he added.


Scott Got­tlieb at a 2016 event. BI­PAR­TI­SAN POL­I­CY CEN­TER

First pub­lished here. Reg­u­la­to­ry Fo­cus is the flag­ship on­line pub­li­ca­tion of the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety (RAPS), the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care and re­lat­ed prod­ucts, in­clud­ing med­ical de­vices, phar­ma­ceu­ti­cals, bi­o­log­ics and nu­tri­tion­al prod­ucts. Email news@raps.org for more in­for­ma­tion.

2023 Spot­light on the Fu­ture of Drug De­vel­op­ment for Small and Mid-Sized Biotechs

In the context of today’s global economic environment, there is an increasing need to work smarter, faster and leaner across all facets of the life sciences industry.  This is particularly true for small and mid-sized biotech companies, many of which are facing declining valuations and competing for increasingly limited funding to propel their science forward.  It is important to recognize that within this framework, many of these smaller companies already find themselves resource-challenged to design and manage clinical studies themselves because they don’t have large teams or in-house experts in navigating the various aspects of the drug development journey. This can be particularly challenging for the most complex and difficult to treat diseases where no previous pathway exists and patients are urgently awaiting breakthroughs.

Dipal Doshi, Entrada Therapeutics CEO

Ver­tex just found the next big ‘trans­for­ma­tive’ thing for the pipeline — at a biotech just down the street

Back in the summer of 2019, when I was covering Vertex’s executive chairman Jeff Leiden’s plans for the pipeline, I picked up on a distinct focus on myotonic dystrophy Type I, or DM1 — one of what Leiden called “two diseases (with DMD) we’re interested in and we continue to look for those assets.”

Today, Leiden’s successor at the helm of Vertex, CEO Reshma Kewalramani, is plunking down $250 million in cash to go the extra mile on DM1. The lion’s share of that is for the upfront, with a small reserve for equity in a deal that lines Vertex up with a neighbor in Seaport that has been rather quietly going at both of Vertex’s early disease targets with preclinical assets.

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Ab­b­Vie slapped with age dis­crim­i­na­tion law­suit, fol­low­ing oth­er phar­mas

Add AbbVie to the list of pharma companies currently facing age discrimination allegations.

Pennsylvania resident Thomas Hesch filed suit against AbbVie on Wednesday, accusing the company of passing him over for promotions in favor of younger candidates.

Despite 30 years of pharma experience, “Hesch has consistently seen younger, less qualified employees promoted over him,” the complaint states.

David Light, Valisure CEO

Val­isure in the hot seat: New Form 483 over a 2021 in­spec­tion as CEO fires back

The notorious drug testing company Valisure, which has made a name for itself by forcing FDA’s hand with some of its safety-related uncoverings, received a letter this week after the FDA uncovered violations at its Connecticut-based testing lab in 2021.

The letter, which was sent on Dec. 5, stated that the FDA is “concerned” that Valisure was not aware of  drug supply chain security requirements.

Mark Cuban (Jed Jacobsohn/AP Images)

Mov­ing to the em­ploy­er side of health­care, Mark Cuban's Cost Plus Drugs part­ners with a PBM

From “Shark Tank” to direct-to-consumer generic drugs, Mark Cuban has made another inroad in the ongoing battle over prescription drug prices. His cost-plus-15% generic drug company, frequently undercutting many competitors, now has its sights set on the employer healthcare market.

Cost Plus Drugs, which originally pledged to cut out PBMs, has now partnered with the PBM EmsanaRx, majority owned by the Purchaser Business Group on Health, to launch a supplemental drug discount program designed specifically for self-funded employers, the company announced Thursday.

WIB22: Am­ber Salz­man had few op­tions when her son was di­ag­nosed with a rare ge­net­ic dis­ease. So she cre­at­ed a bet­ter one

This profile is part of Endpoints News’ 2022 special report about Women in Biopharma R&D. You can read the full report here.

Amber Salzman’s life changed on a cold, damp day in Paris over tiny plastic cups of lukewarm tea.

She was meeting with Patrick Aubourg, a French neurologist studying adrenoleukodystrophy, or ALD, a rare genetic condition that causes rapid neurological decline in young boys. It’s a sinister disease that often leads to disability or death within just a few years. Salzman’s nephew was diagnosed at just 6 or 7 years old, and died at the age of 12.

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Ahead of ad­comm, FDA rais­es un­cer­tain­ties on ben­e­fit-risk pro­file of Cy­to­ki­net­ic­s' po­ten­tial heart drug

The FDA’s Cardiovascular and Renal Drugs Advisory Committee will meet next Tuesday to discuss whether Cytokinetics’ potential heart drug can safely reduce the risk of cardiovascular death and heart failure in patients with symptomatic chronic heart failure with reduced ejection fraction.

The drug, known as omecamtiv mecarbil and in development for more than 15 years, has seen mixed results, with a first Phase III readout from November 2020 hitting the primary endpoint of reducing the odds of hospitalization or other urgent care for heart failure by 8%. But it also missed a key secondary endpoint analysts had pegged as key to breaking into the market.

Bags of shred­ded docs: In­di­an drug­mak­er Lupin hand­ed a Form 483 by FDA in­spec­tors

The generics manufacturer Lupin has been given another Form 483 from the FDA this year.

US regulators inspected Lupin’s pharmaceutical manufacturing site in the town of Mandideep, India from Nov. 14 through Nov. 23, with the 14-page report marking 16 observations.

The inspection report stated that the site did not have the appropriate controls over its computer systems to ensure that changes in “master production” or records are only done by authorized personnel, along with written procedures not being established to conduct annual reviews of records associated with drug batches.

Rami Elghandour, Arcellx CEO

Up­dat­ed: Gilead, Ar­cel­lx team up on an­ti-BC­MA CAR-T as biotech touts a 100% re­sponse rate at #ASH22

Gilead and Kite are plunking down big cash to get into the anti-BCMA CAR-T game.

The pair will shell out $225 million in cash upfront and $100 million in equity to Arcellx, Kite announced Friday morning, to develop the biotech’s lead CAR-T program together. Kite will handle commercialization and co-development with Arcellx, and profits in the US will be split 50-50.

Concurrent with the deal, Arcellx revealed its latest cut of data for the program known as CART-ddBCMA, ahead of a full presentation at this weekend’s ASH conference — a 100% response rate among patients getting the therapy. Investors jumped at the dual announcements, sending Arcellx shares $ACLX up more than 25% in Friday’s morning session.

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