Rep. Andy Harris (R-MD) (Tasos Katopodis/Pool via AP Images)

Up­dat­ed: The mi­cro-cap that tapped a mask-skep­tic con­gress­man for their Covid DSMB is ap­ply­ing for an EUA. Their ev­i­dence? 21 pa­tients

Pub­lish­ers note: Af­ter this re­port was pub­lished, Neu­roRx CEO Jonathan Javitt emailed End­points with more in­for­ma­tion on the DSMB, which we added to the sto­ry. He got in touch again, and sug­gest­ed the sto­ry wasn’t true. We stand by our sto­ry. And I’ve de­cid­ed to pub­lish Javitt’s email re­sponse to this sto­ry in its en­tire­ty. It ap­pears in­line next to each point of con­tention.

—Ar­salan Arif, pub­lish­er

Neu­roRx, the tiny biotech that came un­der fire last week af­ter Politi­co re­port­ed they se­lect­ed a con­gress­man and two oth­er ac­quain­tances of the CEO to su­per­vise their Covid-19 drug tri­al, an­nounced to­day that they will ask the FDA to au­tho­rize their drug based on the re­sults of just 21 pa­tients.

(NOT TRUE.  Ja­son Mast has no idea what da­ta the FDA is look­ing at.  It’s far more than 21 pa­tients — Jonathan Javitt)

Such an ap­pli­ca­tion would test the agency’s stan­dards of ev­i­dence for an EUA, which have al­ready come un­der scruti­ny af­ter con­tro­ver­sial au­tho­riza­tions for con­va­les­cent plas­ma and hy­drox­y­chloro­quine. The on­ly oth­er com­pa­ny to dis­cuss their in­ten­tion to file for an EUA, Eli Lil­ly, did so af­ter re­sults came back from a ran­dom­ized con­trol study test­ing their an­ti­body in over 450 pa­tients.

Both EUAs came amid per­sis­tent pub­lic lob­by­ing from Pres­i­dent Trump and one, hy­drox­y­chloro­quine, was lat­er re­scind­ed. Its au­tho­riza­tion had been based on­ly on lab da­ta and a cou­ple small and much-cri­tiqued stud­ies.

Su­san El­len­berg

Su­san El­len­berg, a for­mer FDA re­view­er and a bio­sta­tis­ti­cian at the Uni­ver­si­ty of Penn­syl­va­nia Perel­man School of Med­i­cine, said an EUA could be war­rant­ed on such lim­it­ed da­ta, but on­ly if the ev­i­dence was over­whelm­ing. She of­fered the hy­po­thet­i­cal of a Phase I study that got mul­ti­ple com­plete re­spons­es in a hard-to-treat metasta­t­ic can­cer.

“If they were all se­vere­ly ill and on ven­ti­la­tors and the treat­ment re­sult­ed in their im­me­di­ate re­cov­ery, test­ing neg­a­tive for the virus and rapid dis­charge from hos­pi­tal, then maybe,” El­len­berg, who had not re­viewed the re­sults, said in an email. “When you achieve some­thing re­al­ly dra­mat­ic in a small num­ber of pa­tients with a fa­tal dis­ease, FDA is pret­ty flex­i­ble.”

Did Neu­roRx meet that thresh­old, though? Of the 21 pa­tients who re­ceived the drug, known as avip­tadil, un­der an ex­pand­ed pro­to­col, 19 sur­vived and sev­en were dis­charged. Sev­en, though, were still in im­me­di­ate care and 5 were in the ICU. Of five pa­tients on EC­MO, three were de­cannu­lat­ed — breath­ing tube re­moved — and two were dis­charged.

David Boul­ware

“The ac­tiv­i­ty of the syn­thet­ic Va­soac­tive In­testi­nal Pep­tide (avip­tadil) ap­pears promis­ing,” Uni­ver­si­ty of Min­neso­ta vi­rol­o­gist David Boul­ware said in an email. “Their re­port­ed re­sults are very good but not earth shat­ter­ing.  With­out a ran­dom­ized con­trol group, what the true ac­tu­al ef­fect is un­known. If high­ly ef­fec­tive, then a small ran­dom­ized clin­i­cal tri­al should be able to quick­ly con­firm these ini­tial re­sults.”

Neu­roRx, which had been de­vel­op­ing a drug for de­pres­sion be­fore piv­ot­ing when the pan­dem­ic hit, launched such a tri­al in March. At the be­gin­ning of Au­gust, CEO Jonathan Javitt tout­ed “overnight re­cov­ery” in a cou­ple of pa­tients who took the drug out­side the Phase II study, un­der an FDA-au­tho­rized ex­pand­ed ac­cess pro­to­col. He said at the time the DSMB had cleared them back in Ju­ly and promised more da­ta would soon come, with an­oth­er re­view sched­uled for Aug. 24, af­ter they en­rolled their 81st pa­tient.

“The re­al­i­ty is, with­in a month, we’re go­ing to have a lot more da­ta,” he told End­points News at the time.  “We’re go­ing to have da­ta from the RCT.”

Those re­sults have yet to ma­te­ri­al­ize, though, and last week, Politi­co raised ques­tions about the DSMB’s com­po­si­tion. Javitt, they re­port­ed, had picked mask-skep­tic Re­pub­li­can con­gress­man Andy Har­ris and two oth­er ac­quain­tances to run the board, rais­ing con­cerns from some ethi­cists who ques­tioned how in­de­pen­dent they could be and how qual­i­fied they were to as­sess whether a tri­al should con­tin­ue. Javitt and Har­ris de­fend­ed the de­ci­sion, point­ing to Har­ris’ med­ical ex­pe­ri­ence.

In an email af­ter pub­li­ca­tion, Javitt said the DSMB al­so in­clud­ed bio­sta­tis­ti­cian Phillip Lavin

(TRUE, Phil has been the sta­tis­ti­cian on more new drug ap­provals than any sta­tis­ti­cian in US his­to­ry — Jonathan Javitt)

… and had nev­er worked di­rect­ly with Al Som­mer, one of the oth­er mem­bers of the DSMB Politi­co re­port­ed,

(I nev­er said that.  It’s read­i­ly ver­i­fi­able that Som­mer and I were co-au­thors on a num­ber of sci­en­tif­ic pa­pers in the 1980s and 90s.  I did tell Politi­co about Som­mer’s cre­den­tials as a Lasker Awardee and mem­ber of the Na­tion­al Acad­e­my of Sci­ences, which of course did not in­ter­est them be­cause their ob­jec­tive was to smear Har­ris. — Jonathan Javitt)

… and had nev­er met Ri­ta Col­well, the oth­er mem­ber, be­fore.

(TRUE — Jonathan Javitt)

Col­well is an aquat­ic bi­ol­o­gist who has not pre­vi­ous­ly served on DSMBs,

(Not True.  Dr. Col­well says she has served be­fore — Jonathan Javitt)

but Javitt said he “want­ed a non-med­ical mem­ber of the com­mit­tee who could un­der­stand the da­ta and still rep­re­sent the lay pub­lic’s point.”

(TRUE, and the FDA guid­ance says to in­clude mem­bers of the pub­lic — Jonathan Javitt)

He said the FDA had re­quest­ed they de­lay the Au­gust 24 meet­ing af­ter the DSMB rec­om­mend­ed a change in end­point. The agency want­ed 21 more pa­tients and have just en­rolled pa­tient num­ber 100. “Like­ly the DSMB will meet in the next four weeks,” he said.

In a press re­lease about the EUA sub­mis­sion, Javitt said they were ap­ply­ing for the EUA be­cause they have dis­cov­ered many hos­pi­tals do not al­low pa­tients ac­cess to ex­per­i­men­tal drugs. They say it would on­ly cov­er pa­tients who have ex­haust­ed oth­er treat­ment op­tions and would have been el­i­gi­ble for the EAP.

“Trag­i­cal­ly, we have found that many pa­tients who might ben­e­fit from the Ex­pand­ed Ac­cess pro­to­col are hos­pi­tal­ized in cen­ters that do not al­low pa­tients ac­cess to in­ves­ti­ga­tion­al drugs,” he said. “Our staff is work­ing around the clock to ad­dress re­quests for RLF-100™ un­der the ap­pro­pri­ate mech­a­nism. All too of­ten, pa­tients of col­or and those of low­er so­cioe­co­nom­ic sta­tus are de­nied ac­cess.”

For a look at all End­points News coro­n­avirus sto­ries, check out our spe­cial news chan­nel.

In his­toric Covid-19 ad­comm, vac­cine ex­perts de­bate a sea of ques­tions — but of­fer no clear an­swers

The most widely anticipated and perhaps most widely watched meeting in the FDA’s 113-year history ended late Thursday night with a score of questions and very few answers.

For nearly 9 hours, 18 different outside experts listened to public health agencies and foundations present how the United States’ Covid-19 vaccine program developed through October, and they debated where it should go from there: Were companies testing the right metrics in their massive trials? How long should they track patients before declaring a vaccine safe or effective? Should a vaccine, once authorized, be given to the volunteers in the placebo arm of a trial?

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Pascal Soriot, AstraZeneca CEO (Zach Gibson/Bloomberg via Getty Images)

UP­DAT­ED: FDA gives As­traZeneca the thumbs-up to restart PhI­II Covid-19 vac­cine tri­als, and J&J is prepar­ing to re­sume its study

Several countries had restarted their portions of AstraZeneca’s global Phase III Covid-19 vaccine trial after the study was paused worldwide in early September, but the US notably stayed on the sidelines — until now. Friday afternoon the pharma giant announced the all clear from US regulators. And on top of that, J&J announced Friday evening that it’s preparing to resume its own Phase III vaccine trial.

Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

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Dan O'Day, Gilead CEO (Andrew Harnik, AP Images)

UP­DAT­ED: FDA anoints Gilead­'s remde­sivir as the Covid-19 treat­ment win­ner, hand­ing down full ap­proval — de­spite some deep skep­ti­cism

Seven months into the Covid-19 pandemic, the race to develop a treatment for the disease that’s proved to be the biggest health crisis in a century has an officially designated winner: Gilead. And they’re picking up the prize — worth billions in peak sales — despite a major study that concluded the drug was no help in reducing the number of people who die from the virus.

The FDA handed down a thumbs-up for remdesivir, the company announced Thursday afternoon, as the drug becomes the first fully approved treatment for Covid-19 in the US. Remdesivir, to be marketed as Veklury, will come with a label for treatment in adults and children older than 12 in Covid-19 cases that require hospitalization.

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Stephen Hoge, Moderna president (Moderna)

On morn­ing of FDA Covid-19 ad­comm, Mod­er­na com­pletes PhI­II en­roll­ment, putting them neck-and-neck with Pfiz­er

Weeks away from a potential EUA application, Moderna announced they have completed enrollment in their 30,000-person Phase III Covid-19 vaccine trial, with over a third of volunteers non-white and a quarter over the age of 65.

The announcement caps what has been the most closely-watched recruitment race in the history of drug development, as Pfizer and Moderna rushed to get enough volunteers to prove whether or not experimental vaccines could actually protect people from contracting Covid-19. Pfizer reached that mark on Sept. 15. Moderna said around the same time that they would slow down enrollment to ensure they enrolled enough participants from minority and at-risk groups.

Ul­tragenyx in­jects $40M to grab Solid's mi­crody­s­trophin trans­gene — while side­step­ping the AAV9 vec­tor that stirred up safe­ty fears

Since before Ilan Ganot started Solid Bio to develop a gene therapy for kids like his son, who has Duchenne muscular dystrophy, Ultragenyx CEO Emil Kakkis has been watching and advising the former investment banker as he navigated the deep waters of drug development.

Just as Solid is getting back up on its feet after a yearlong clinical hold, Kakkis has decided to jump in for a formal alliance.

With a $40 million upfront, Ultragenyx is grabbing 14.45% of Solid’s shares $SLDB and the rights to its microdystrophin construct for use in combination with AAV8 vectors. Solid’s lead program, which utilizes AAV9, remains unaffected. The company also retains rights to other applications of its transgene.

A top drug pro­gram at Bay­er clears a high bar for CKD — open­ing the door to an FDA pitch

Over the past 4 years, Bayer has been steering a major trial through a pivotal program to see if their drug finerenone could slow down the pace of chronic kidney disease in patients suffering from both CKD as well as Type 2 diabetes.

Today, their team jumped on a virtual meeting hosted by the American Society of Nephrology to offer a solid set of pivotal data to demonstrate that the drug can delay dialysis or a kidney replacement as well as cardio disease, while also adding some worrying signs of hyperkalemia among the patients taking the drug. And they’re hustling it straight to regulators in search of an approval for kidney disease and cardio patients — one of the toughest challenges in the book, as demonstrated by repeated past failures.

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Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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Covid-19 roundup: An mR­NA play­er gets a boost out of the lat­est round of an­i­mal da­ta; Phase­Bio pulls the plug on treat­ment tri­al

The big tell for CureVac $CVAC is coming up with a looming early-stage readout on their mRNA Covid-19 vaccine in the clinic. But for now they’ll make do with an upbeat assessment on the preclinical animal data they used to get into the clinic.

Researchers for the German biotech say they got the high antibody titers and T cell activation they were looking for, lining up a hamster challenge to demonstrate — in a simple model — that the vaccine could protect the furry creatures. Like the other mRNA vaccines, the drug sends instructions to spur cells to decorate themselves with the distinctive spike on the virus to elicit an immune response.