Pa­tient ex­pe­ri­ence da­ta: Sanofi re­searchers call for more con­sis­ten­cy from FDA

Re­searchers at drug­mak­er Sanofi are call­ing on the FDA to make its pub­li­ca­tion of pa­tient ex­pe­ri­ence da­ta (PED) in re­view doc­u­men­ta­tion more con­sis­tent af­ter re­view­ing ap­pli­ca­tions ap­proved in the first full year af­ter a re­quire­ment of the 21st Cen­tu­ry Cures Act com­pelled the agency to do so.

Un­der Sec­tion 3001 of the 21st Cen­tu­ry Cures Act, the FDA is re­quired to “pub­lish a brief state­ment on any pa­tient ex­pe­ri­ence da­ta or re­lat­ed in­for­ma­tion that was part of the ap­pli­ca­tion” for ap­pli­ca­tions sub­mit­ted af­ter 16 June 2017.

In 2018, the FDA’s Cen­ter for Drug Eval­u­a­tion and Re­search (CDER) ap­proved 59 nov­el drugs and bi­o­log­ics. Of those, 48 ap­pli­ca­tions (81.4%) in­clud­ed a Sec. 3001 PED ta­ble with­in the re­view doc­u­men­ta­tion. Among the 11 prod­ucts that did not in­clude a PED ta­ble, sev­en were sub­mit­ted to the FDA pri­or to the im­ple­men­ta­tion date for Sec. 3001.

Among the 48 ap­pli­ca­tions that in­clud­ed a PED ta­ble, the re­searchers found that 34 (70.8%) re­port­ed us­ing PED dur­ing the re­view. Of those 34 ap­pli­ca­tions, 29 (60.4%) in­clud­ed on­ly spon­sor-sub­mit­ted PED, four (8.3%) in­clud­ed spon­sor- and non­spon­sor-sub­mit­ted PED and one (2.1%) in­clud­ed on­ly non­spon­sor-sub­mit­ted PED.

The sources of the non­spon­sor-sub­mit­ted PED in­clud­ed the FDA pa­tient-fo­cused drug de­vel­op­ment meet­ing sum­maries, a meet­ing be­tween the FDA and pa­tient stake­hold­ers and an FDA ad­vi­so­ry com­mit­tee meet­ing.

The re­searchers al­so re­viewed the use of PED across prod­ucts with spe­cial reg­u­la­to­ry des­ig­na­tions, in­clud­ing or­phan drug des­ig­na­tion, break­through ther­a­py des­ig­na­tion, fast track des­ig­na­tion, pri­or­i­ty re­view and ac­cel­er­at­ed ap­proval.

Con­trary to their ex­pec­ta­tions, the re­searchers found that ap­pli­ca­tions with or­phan des­ig­na­tion were less like­ly to in­clude PED in their re­view doc­u­men­ta­tion, with 60.7% of ap­pli­ca­tions with or­phan des­ig­na­tion in­clud­ing PED com­pared to 85% of non-or­phan ap­pli­ca­tions uti­liz­ing PED as part of their re­view.

The re­searchers ob­served a sim­i­lar trend for ap­pli­ca­tions that re­ceived fast track sta­tus or a pri­or­i­ty re­view, not­ing that 61.9% of ap­pli­ca­tions with fast track sta­tus and 64.9% of pri­or­i­ty re­views in­clud­ed PED, while 77.8% of non-fast track and 90.9% non-pri­or­i­ty re­view ap­pli­ca­tions in­clud­ed PED.

On the oth­er hand, prod­ucts grant­ed break­through ther­a­py des­ig­na­tion or ac­cel­er­at­ed ap­proval were more like­ly to in­clude PED in their re­view doc­u­men­ta­tion.

“In­clu­sion of the PED ta­ble with­in the FDA Re­view Doc­u­men­ta­tion—which are by na­ture high­ly tech­ni­cal and ac­cessed pri­mar­i­ly by spon­sors and aca­d­e­mics—would lim­it their vis­i­bil­i­ty to stake­hold­ers less fa­mil­iar with the FDA reg­u­la­to­ry process (such as pa­tient groups and health­care providers),” the re­searchers write.

The re­searchers al­so point out that while the for­mat of the PED ta­bles in­clud­ed in the re­view doc­u­men­ta­tion were “large­ly con­sis­tent through­out these 48 drug prod­uct ap­pli­ca­tions, the use of the ta­ble by FDA re­view­ers var­ied sig­nif­i­cant­ly,” not­ing that in just over half of the ap­pli­ca­tions (58.3%) the PED ta­ble spec­i­fied the ap­pli­ca­tion sec­tion where PED was dis­cussed. Ad­di­tion­al­ly, the re­searchers say that on­ly nine of the 29 ap­pli­ca­tions that in­clud­ed pa­tient re­port­ed out­come (PRO) da­ta spec­i­fied which PRO in­stru­ment was used.

“Fur­ther, it ap­pears that FDA did not con­sis­tent­ly pub­lish a PED ta­ble for sup­ple­men­tal ap­pli­ca­tions, which are al­so ap­proved un­der FD&C Act 505(b) or PH­SA 351(a)—while this in­for­ma­tion some­times can be ac­cessed by oth­er means, there is no con­sol­i­dat­ed, ‘pub­licly avail­able’ ac­cess to this in­for­ma­tion,” the re­searchers write.

The re­searchers high­light the fact that clin­i­cal out­come as­sess­ments (COAs), in­clud­ing PROs, ac­count­ed for near­ly three-quar­ters (73.2%) of the sources of PED in the ap­pli­ca­tions.

While the re­searchers note that this may be due to both spon­sors and the FDA hav­ing more ex­pe­ri­ence with COAs com­pared to oth­er sources of PED. “Based on the re­sults of this re­view, both the FDA and spon­sors should en­sure that all forms of PED, be­yond COAs, are ap­pro­pri­ate­ly be­ing in­cor­po­rat­ed in­to drug de­vel­op­ment,” they write.

Look­ing ahead, the re­searchers say they ex­pect the FDA to be more con­sis­tent in its han­dling of PED across its re­view di­vi­sions and ar­gue that the re­quire­ments un­der Sec­tion 3001 of the Cures Act should ap­ply to sup­ple­men­tal ap­pli­ca­tions as well.

Ad­di­tion­al­ly, the re­searchers say that the FDA could make its use of PED more ac­ces­si­ble by in­clud­ing a plain lan­guage “pa­tient-fac­ing state­ment de­scrib­ing FDA’s use and ap­pli­ca­tion of PED for each ap­proval,” sim­i­lar to how the agency pro­vides its drug tri­al snap­shots.

The re­searchers al­so ar­gue that the FDA should in­clude or link to its use of PED in its re­views of ap­pli­ca­tions in ap­proved la­bel­ing. “With­out di­rect in­clu­sion in la­bel­ing, or at least a mean­ing­ful and ac­ces­si­ble link­age of the in­for­ma­tion to la­bel­ing, true pub­li­ca­tion of FDA’s use of pa­tient in­put ar­guably has not been ef­fec­tu­at­ed for the ben­e­fit of all users,” the re­searchers write.

FDA Re­port­ed Use of Pa­tient Ex­pe­ri­ence Da­ta in 2018 Drug Ap­provals


RAPS: First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.

Lessons for biotech and phar­ma from a doc­tor who chased his own cure

After being struck by a rare disease as a healthy third year medical student, David Fajgenbaum began an arduous journey chasing his own cure. Amidst the hustle of this year’s JP Morgan conference, the digital trials platform Medable partnered with Endpoints Studio to share Dr. Fajgenbaum’s story with the drug development industry.

What follows is an edited transcript of the conversation between Medable CEO Dr. Michelle Longmire and Dr. Fajgenbaum, and it is full of lessons for biotech executives charged with bringing the next generation of medicines to patients.

Jim Scholefield via PR Newswire

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Tim Mayleben (file photo)

Es­pe­ri­on's goldilocks cho­les­terol fight­er wins FDA ap­proval — will its 'tra­di­tion­al' pric­ing ap­proach spur adop­tion?

It’s more effective than decades-old statins but not as good as the injectable PCSK9 — the goldilocks treatment for cholesterol-lowering, bempedoic acid, has secured FDA approval.

Its maker, Esperion Therapeutics, is betting that their pricing strategy — a planned list price of between $10 to $11 a day — will help it skirt the pushback the PCSK9 cholesterol fighters, Repatha and Praluent, got from payers for their high sticker prices.

The sky-high expectations for the pair of PCSK9 drugs that were first approved in 2015 quickly simmered — and despite a 60% price cut, coupled with data showing the therapies also significantly cut cardiovascular risk, sales have not really perked up.

Esperion is convinced that by virtue of being a cheaper oral therapy, bempedoic acid will hit that sweet spot in terms of adoption.

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James Collins, Broad Institute via Youtube

UP­DAT­ED: A space odyssey for new an­tibi­otics: MIT's ma­chine learn­ing ap­proach

Drug development is complex, expensive and comes with lousy odds of success — but in most cases, if you make it across the finish line brandishing a product with an edge (and play your cards right) it can be a lucrative endeavor.

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Gilead los­es two more patent chal­lenges on HIV pill, set­ting up court­room fight in Delaware

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Kathy High (file photo)

Gene ther­a­py pi­o­neer Kathy High has left Spark af­ter com­plet­ing $4.3B union with Roche

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Tal Zaks (Moderna via YouTube)

For two decades, a new vac­cine tech­nol­o­gy has been slow­ly ap­proach­ing prime time. Now, can it stop a pan­dem­ic?

Two months before the outbreak, Moderna CMO Tal Zaks traveled from Cambridge, MA to Washington DC to meet with Anthony Fauci and the leaders of the National Institutes of Health.

For two years, Moderna had worked closely with NIH researchers to build a new kind of vaccine for MERS, one of the deadliest new viruses to emerge in the 21st century. The program was one test for a new technology designed to be faster, cheaper and more precise than the ways vaccines had been made for over a century. They had gathered evidence the technology could work in principle, and Fauci, the longtime head of the National Institute of Allergy and Infectious Diseases and a longtime advocate for better epidemic preparedness, wanted to see if it, along with a couple of other approaches, could work in a worst-case scenario: A pandemic.

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Zaks and Fauci, of course, wouldn’t have to wait to develop a new test. By year’s end, an outbreak in China would short circuit the need for one and throw them into 24/7 work on a real-world emergency. They also weren’t the only ones with new technology who saw a chance to help in a crisis.

An ocean away, Lidia Oostvogels was still on vacation and relaxing at her mother’s house in Belgium when her Facebook started changing. It was days after Christmas and on most people’s feeds, the news that China had reported a novel virus to the World Health Organization blurred into the stream of holiday sweaters and fir trees. But on Oostvogels’s feed, full of vaccine researchers and virus experts, speculation boiled: There was a virus in China, something contained to the country, but “exotic,” “weird,” and maybe having to do with animals. Maybe a coronavirus.

Lidia Oostvogels

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Christos Kyratsous (via LinkedIn)

He built a MERS treat­ment in 6 months and then the best Ebo­la drug. Now Chris­tos Kyrat­sous turns his sights on Covid-19

TARRYTOWN, NY — In 2015, as the Ebola epidemic raged through swaths of West Africa, Kristen Pascal’s roommates sat her down on their couch and staged an intervention.

“Are you sure this is what you want to be doing with your life?” she recalls them asking her.

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Pascal, a research associate for Regeneron, had been coming home at 2 am and leaving at 6 am. At one point, she didn’t see her roommate for a week. For months, that was life in Christos Kyratsous’ lab as the pair led a company-wide race to develop the first drug that could effectively treat Ebola before the outbreak ended. For Pascal, that was worth it.

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Last August, Regeneron learned they had succeeded: In a large trial across West Africa, their drug, REGN-EB3, was vastly more effective than the standard treatments. It was surprise news for the company, coming just 10 months into a trial they thought would take several years and a major victory in the global fight against a deadly virus that killed over 2,000 in 2019 and can carry a mortality rate of up to 90%.

For Kyratsous and Pascal, though, it brought only fleeting reprieve. Just four months after the NIH informed them REGN-EB3 worked, Kyratsous was back in his office reading the New York Times for updates on a new outbreak on another continent, and wondering alongside Pascal and senior management whether it was time to pull the trigger again.

In late January, as the death toll swelled and the first confirmed cases outside China broke double digits, they made a decision. Soon they were back on the phone with the multiple government agencies and their coronavirus partners at the University of Maryland’s Level 3 bio lab. The question was simple: Can Kyratsous and his team use a process honed over two previous outbreaks, and create a treatment before the newest epidemic ends? Or worse, if, as world health experts fear, it doesn’t vanish but becomes a recurrent virus like the flu?

“Christos likes things immediately,” Matt Frieman, Regeneron’s coronavirus collaborator at the University of Maryland, told Endpoints. “That’s what makes us good collaborators: We push each other to develop things faster and faster.”

Kristen Pascal (Regeneron)

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The first time Regeneron tried to respond to a global outbreak, it was something of a systems test, Kyratsous explains from his office at Regeneron’s Tarrytown headquarters. Kyratsous, newly promoted, has crammed it with photos of his family, sketches of viral vectors and a shark he drew for his 3-year-old son. He speaks rapidly – an idiosyncrasy his press person says has only been aggravated this afternoon by the contents of his “Regeneron Infectious Diseases”-minted espresso glass – and he gesticulates with similar fluidity, tumbling through antibodies, MERS, the novel coronavirus, Ebola-infected monkeys.

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Bank­rupt an­tibi­otics mak­er Ar­a­digm turns to old part­ner/in­vestor for fi­nal $3M fire sale

Grifols once paid Aradigm $26 million for a stake in its inhaled antibiotics. But with Aradigm now in bankruptcy, the Spanish drugmaker is dishing out a final $3.2 million to buy it all.

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