Robert Califf and Richard Pazdur speak at the annual Friends of Cancer Research event (Credit: Friends of Cancer Research via Twitter)

FDA lead­ers Califf and Paz­dur dish on ac­cel­er­at­ed ap­proval re­forms, sin­gle-coun­try tri­als and an emp­ty White Oak

FDA Com­mis­sion­er Rob Califf sat down for a con­ver­sa­tion on Thurs­day morn­ing with Rick Paz­dur, head of the FDA’s On­col­o­gy Cen­ter of Ex­cel­lence, with the two agree­ing that ac­cel­er­at­ed ap­proval re­forms need to hap­pen, that mul­ti-re­gion­al clin­i­cal tri­als are al­ways bet­ter than sin­gle-coun­try tri­als, and that re­turn­ing every last FDAer to the White Oak cam­pus doesn’t make sense.

The con­ver­sa­tion, con­duct­ed as part of the Friends of Can­cer Re­search’s an­nu­al meet­ing, be­gan with Califf’s ques­tions on the emp­ty space around White Oak as rou­tine staff have most­ly moved their op­er­a­tions to the more ver­sa­tile vir­tu­al set­ting, and as ad­vi­so­ry com­mit­tee and all in­dus­try meet­ings re­main vir­tu­al.

Paz­dur even went so far as to call White Oak “de­sert­ed,” not­ing that “there are more se­cu­ri­ty guards than em­ploy­ees.” But he al­so made clear that it doesn’t make sense to re­quire every­one to re­turn to an in-per­son of­fice.

“What is the pur­pose of go­ing back? To make an ad­min­is­tra­tor hap­py?” Paz­dur asked rhetor­i­cal­ly, say­ing that the clock-punch­ing men­tal­i­ty of years past needs to be rethought giv­en the work­load and work­force.

Califf not­ed that in­dus­try has been “loud and clear” about want­i­ng to re­turn to in-per­son meet­ings, but a more hy­brid en­vi­ron­ment may be what the FDA set­tles on mov­ing for­ward to re­main ag­ile.

On the top­ic of ac­cel­er­at­ed ap­proval re­forms, which De­moc­rats ini­tial­ly sought to in­clude in the user fee leg­is­la­tion but may end up deal­ing with in this lame duck ses­sion, Paz­dur re­it­er­at­ed what he wrote in the New Eng­land Jour­nal of Med­i­cine in Sep­tem­ber about clean­ing up the con­fir­ma­to­ry tri­al process.

“There’s a pe­ri­od of vul­ner­a­bil­i­ty we have to con­trol,” Paz­dur told Califf, not­ing that from ac­cel­er­at­ed ap­proval an­nounce­ment to con­fir­ma­tion of clin­i­cal ben­e­fit, “we should try to re­duce that pe­ri­od as much as pos­si­ble.”

For on­col­o­gy in­di­ca­tions that have been grant­ed AAs, the me­di­an time to be­gin­ning the with­draw­al process “was longer if the con­fir­ma­to­ry tri­al was ini­ti­at­ed af­ter the ap­proval,” Paz­dur and OCE lead­ers wrote in the NE­JM. “This dif­fer­ence was most strik­ing among with­drawn in­di­ca­tions, with a me­di­an time to with­draw­al of 3.8 years if the con­fir­ma­to­ry tri­al was on­go­ing at the time of AA, as com­pared with 7.3 years if such a tri­al had not been ini­ti­at­ed. De­layed with­drawals in this lat­ter sce­nario rep­re­sent the great­est risk to pa­tients.”

Paz­dur al­so told the con­fer­ence and Califf that larg­er com­pa­nies are large­ly ad­her­ing to the FDA’s re­quests when it comes to with­draw­ing AAs, “but we get in­to trou­ble with a com­pa­ny that may not be ad­e­quate­ly cap­i­tal­ized,” not­ing the sys­tem needs to be more nim­ble and sug­ges­tions float­ed in Con­gress on var­i­ous ways to ex­pe­dite the re­moval of these drugs, or even dif­fer­en­tial charg­ing for drugs un­der AA com­pared to prices for full ap­provals.

“When I came to the agency in 1999, I re­al­ized this was a prob­lem and with your pre­de­ces­sor, I sug­gest­ed that drugs un­der ac­cel­er­at­ed ap­proval not be con­sid­ered avail­able ther­a­py and my rea­son for that was that this would make com­pa­nies want to do these stud­ies as quick­ly as pos­si­ble. Un­for­tu­nate­ly that didn’t work,” Paz­dur said.

While not­ing that he al­so high­ly val­ues the AA path­way, Califf added that “we need more teeth,” par­tic­u­lar­ly on get­ting those con­fir­ma­to­ry tri­als start­ed pri­or to the ap­proval. “Once the ap­proval oc­curs, it’s very hard to hold back mar­ke­teers,” Califf added.

On the ques­tion of sin­gle-coun­try tri­als, fol­low­ing FDA’s re­jec­tion of Eli Lil­ly’s at­tempt to bring an­oth­er PD-1 can­cer drug with Chi­na-on­ly da­ta to the US mar­ket, Paz­dur made clear that the FDA fa­vors mul­ti-re­gion­al tri­als.

“We’re not sug­gest­ing  that all clin­i­cal tri­als have to be done in the Unit­ed States or a per­cent­age has to be done in the Unit­ed States, but we want rep­re­sen­ta­tion of all of the ICH re­gions,” in­clud­ing North Amer­i­ca, Eu­rope and Asia, Paz­dur said.

He al­so not­ed that some­times com­pa­nies move tri­als out­side the US be­cause of cost is­sues, which “might be a rea­son­able is­sue,” but “one of my prob­lems” is when com­pa­nies will use sin­gle-coun­try tri­als be­cause they can test the in­ves­ti­ga­tion­al prod­uct against an in­fe­ri­or ther­a­py and that tri­al wouldn’t be eth­i­cal­ly run in the US. He added:

I think this is par­tic­u­lar­ly prob­lem­at­ic. One of the rea­son peo­ple go on clin­i­cal tri­als is to get the best ther­a­pies. There’s no as­ter­isk that says on­ly ap­proved in your coun­try. Peo­ple are go­ing to lose con­fi­dence in the sys­tem if they know tri­als are done with in­fe­ri­or treat­ments.

“These com­pa­nies are not Moth­er There­sa here, they’re us­ing pa­tients here, and we have to al­ways make sure pa­tients aren’t con­sid­ered com­modi­ties,” Paz­dur added.

Califf said there is a prob­lem of peo­ple leav­ing the US for treat­ment and tri­als, and Paz­dur not­ed that the US clin­i­cal tri­al ecosys­tem needs to be sim­pli­fied as pa­tient con­sent forms can still run 20 pages long.

On that note, OCE is launch­ing “Pro­ject Prag­mat­i­ca” along­side the Na­tion­al Can­cer In­sti­tute to sim­pli­fy cer­tain tri­als with drugs that have known safe­ty pro­files, and can an­swer ques­tions on over­all sur­vival more rapid­ly with a prag­mat­ic tri­al that pre­serves ran­dom­iza­tion.

Both Paz­dur and Califf agreed that the key here is ran­dom­iza­tion. “Ex­ter­nal con­trols have lim­i­ta­tions and the beau­ty of ran­dom­iza­tion re­al­ly is to take and ad­dress fac­tors we don’t know about,” Paz­dur said.

Up­dat­ed: FDA re­mains silent on or­phan drug ex­clu­siv­i­ty af­ter last year's court loss

Since losing a controversial court case over orphan drug exclusivity last year, the FDA’s Office of Orphan Products Development has remained entirely silent on orphan exclusivity for any product approved since last November, leaving many sponsors in limbo on what to expect.

That silence means that for more than 70 orphan-designated indications for more than 60 products, OOPD has issued no public determination on the seven-year orphan exclusivity in the Orange Book, and no new listings of orphan exclusivity appear in OOPD’s searchable database, as highlighted recently by George O’Brien, a partner in Mayer Brown’s Washington, DC office.

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Y-mAbs said it’s disappointed “but not surprised” given that the agency’s oncology drug advisory committee had voted 16-0 against its drug’s approval a few weeks ago.

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Rigel Phar­ma scores FDA ap­proval for leukemia, kick­ing off show­down with Servi­er in IDH1

When Rigel Pharma bought olutasidenib from Forma Therapeutics, it acquired a drug that already secured a PDUFA date at the FDA — for February 2023. But regulators are ready to give their OK sooner than that.

The FDA has approved the IDH1 inhibitor as a treatment for adult patients with relapsed or refractory acute myeloid leukemia who have a susceptible IDH-1 (isocitrate dehydrogenase-1) mutation as detected by an FDA-greenlit test. Rigel will market it as Rezlidhia.

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He’ll trade in his Amgen hat for chief scientist at a machine learning startup that has reeled in hundreds of millions in capital to lay the groundwork for a much-hyped new model of drug discovery that aims to speed up the time to new clinical assets.

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In a big week for Carrick Therapeutics, the company announced $60 million in funding for its lead breast cancer drug and development of a second program, as well as a collaboration with Pfizer for combo development.

The $35 million from Pfizer comes with an agreement under which Pfizer will support Carrick’s Phase II study of samuraciclib in combination with Pfizer’s Faslodex for advanced breast cancer. Along with the investment, Adam Schayowitz, vice president and development head of breast cancer, colorectal cancer and melanoma at Pfizer global product development, will join Carrick’s scientific advisory board.

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Paul Hudson, Sanofi CEO (Romuald Meigneux/Sipa via AP Images)

Sanofi and Am­gen are bring­ing cash to cov­er the ta­ble stakes for the Hori­zon M&A game

With the market cap on Horizon Therapeutics $HZNP pushed up to the $23 billion mark today, one of the Big Pharmas in the hunt for a major league buyout deal signaled it’s playing the M&A game with cash.

Paris-based Sanofi, where CEO Paul Hudson has been largely focused on some risky biotech acquisitions to win some respect for its future pipeline prospects, issued a statement early Friday — complying with Rule 2.12 of the Irish takeover rules — making clear that while the certainty or size of an offer can’t be determined, any offer “will be solely in cash.” And Amgen CEO Robert Bradway came right in behind him, filing a statement on the London Stock Exchange overnight that any offer they may make will “likely” be in cash as well.

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Illustration: Assistant Editor Kathy Wong for Endpoints News

As mon­ey pours in­to dig­i­tal ther­a­peu­tics, in­sur­ance cov­er­age crawls



Talk therapy didn’t help Lily with attention deficit hyperactivity disorder, or ADHD. But a video game did.

As the 10-year-old zooms through icy waters and targets flying creatures on the snow-capped planet Frigidus, she builds attention skills, thanks to Akili Interactive Labs’ video game EndeavorRx. She’s now less anxious and scattered, allowing her to stay on a low dose of ADHD medication, according to her mom Violet Vu.

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Eli Lil­ly’s Alzheimer’s drug clears more amy­loid ear­ly than Aduhelm in first-ever head-to-head. Will it mat­ter?

Ahead of the FDA’s decision on Eli Lilly’s Alzheimer’s drug donanemab in February, the Big Pharma is dropping a first cut of data from one of the more interesting trials — but less important in a regulatory sense — at an Alzheimer’s conference in San Francisco.

In the unblinded 148-person study, Eli Lilly pitted its drug against Aduhelm, Biogen’s drug that won FDA approval but lost Medicare coverage outside of clinical trials. Notably, the study didn’t look at clinical outcomes, but rather the clearance of amyloid, a protein whose buildup is associated with Alzheimer’s disease, in the brain.

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Ar­genx pur­chas­es $100M+ FDA pri­or­i­ty re­view vouch­er from blue­bird bio

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The Netherland-based biotech picked up the PRV from bluebird bio, the companies announced on Wednesday. PRVs shorten a drug’s FDA review period from 10 months to 6 months, though they often sell on the open market for around $100 million each.

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