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.

Big Phar­ma's Twit­ter ex­o­dus; Mer­ck wa­gers $1.35B on buy­out; $3.5M gene ther­a­py; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

As you start planning for #JPM23, we hope you will consider joining Endpoints News for our live and virtual events. For those who are celebrating Thanksgiving, we hope you are enjoying the long weekend with loved ones. And if you’re not — we’ll see you next week!

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Paul Perreault, CSL Behring CEO

CSL lands FDA ap­proval for he­mo­phil­ia B gene ther­a­py, sets $3.5M list price

The FDA has approved the world’s first gene therapy for hemophilia B, ushering into the market a treatment that’s historic in both what it promises to do and how much it will cost.

CSL will be marketing the drug, Hemgenix, at a list price of $3.5 million — which sets a new record for the most expensive single-use gene therapy in the US.

In a statement provided to Endpoints News, the Australian company noted that the current costs of treating people with moderate to severe hemophilia B can be significant over a lifetime. By some estimates, healthcare systems could spend more than $20 million per person.

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Elon Musk (GDA via AP Images)

Biggest drug com­pa­nies halt­ed Twit­ter ad buys af­ter Lil­ly in­sulin spoof

Almost all of the drug industry’s biggest advertisers cut their spending on Twitter to zero or near-zero over the last two weeks amid worries about impersonation of their brands by pranksters and the future of the social media company.

Among 18 of the biggest pharmaceutical advertisers in the US market, 12 cut their Twitter ad spending to nothing for the week beginning Nov. 14, according to Pathmatics, which tracks data on prescription drug ad spending as well as general corporate advertising. The list of drugmakers cutting spending to zero includes Merck, AstraZeneca, Eli Lilly, Novartis, Pfizer and others.

Rob Davis, Merck CEO

Up­dat­ed: No Seagen here: 'Do more' means a small $1.35B pur­chase of Ima­go for Mer­ck

Merck is making an acquisition, the Big Pharma announced before Monday’s opening bell. No, Seagen is not entering the fold, as had been speculated for quarters.

Folding under Merck’s wings will be Pfizer-backed Imago BioSciences. For nearly a year, Merck CEO Rob Davis has been saying the pharma giant needs to “do more” on the business development front after its 2021 $11.5 billion acquisition of Acceleron.

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FDA preps for DMD drug gener­ics as Sarep­ta has yet to fin­ish its con­fir­ma­to­ry tri­al

The FDA typically releases guidance to help generic drug manufacturers develop new copycats of small molecule drugs, oftentimes in preparation for a brand name product’s patents or exclusivity to expire.

This week, FDA released such bioequivalence guidance for any generic drugmakers looking to take on Sarepta’s Duchenne muscular dystrophy (DMD) drug Exondys 51 (eteplirsen), even though the drug’s sponsor has yet to convert the accelerated approval to a full approval, showing clinical benefit.

Alzheimer’s drug bites the dust; Re­struc­ture, re­struc­ture, re­struc­ture; Land­mark di­a­betes OK; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

Being in the news business can give one a warped sense of time — it feels like quite a while since we published some of these stories below. But next Saturday’s Endpoints Weekly will definitely be shorter, as we take off Thursday and Friday for Thanksgiving. We will still have the abbreviated edition in your inbox at the usual time.

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Days af­ter re­port­ing PhI­II fail­ure, GSK pulls BC­MA drug from US mar­ket — but it's not giv­ing up en­tire­ly yet

GSK is pulling its BCMA-targeting drug from the US market, ending a short, two-year run for a high-profile product that, among other things, was hailed for marking the pharma giant’s return to oncology.

The company is initiating the process for withdrawal at the request of the FDA, which in turn was based on the negative readout of a confirmatory Phase III trial earlier this month. In that trial, GSK’s Blenrep failed to extend progression-free survival over standard of care for patients with multiple myeloma who have received at least two prior lines of therapy.

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Image: Shutterstock

MIT re­searchers re­veal DNA "Paste" tech be­hind lat­est gene edit­ing start­up

MIT scientists have developed a tool that they say can insert large gene sequences where they want in the genome.

In a paper published Thursday in Nature Biotechnology, MIT fellows Omar Abudayyeh, Jonathan Gootenberg and colleagues detail a technology they call PASTE, which they say can potentially be used to insert long strands of DNA and treat genetic diseases caused by many different mutations, such as cystic fibrosis and Leber congenital amaurosis, a rare eye disorder that causes blindness.

J&J's Spra­va­to pulls a PhI­II win against Sero­quel XR in treat­ment-re­sis­tant de­pres­sion

A day before Thanksgiving, J&J’s Janssen has a new cut of Phase III Spravato data to be grateful for.

The pharma giant announced on Wednesday that its nasal spray, also known as esketamine, beat extended-release quetiapine, previously sold by AstraZeneca as Seroquel XR, in treatment-resistant depression (TRD). Of 676 adults, a significantly higher number of patients on Spravato were able to achieve remission and avoid relapse after 32 weeks, according to J&J.