Flu­vox­am­ine, an SS­RI al­ready FDA-ap­proved as an OCD treat­ment, ap­peared to show some hints of ef­fi­ca­cy in Covid-19 too, lead­ing Uni­ver­si­ty of Min­neso­ta ID doc David Boul­ware last De­cem­ber to sub­mit an EUA for it as an out­pa­tient treat­ment for those test­ing pos­i­tive and to pre­vent the pro­gres­sion to hos­pi­tal­iza­tion.

Al­most 6 months lat­er, the FDA said Mon­day it’s re­ject­ing the cheap gener­ic drug’s Covid-19 EUA as the pri­ma­ry RCT from Brazil, on which the ma­jor­i­ty of the app rests: “The treat­ment ben­e­fit of flu­vox­am­ine was not per­sua­sive when fo­cus­ing on clin­i­cal­ly mean­ing­ful out­comes such as pro­por­tion of pa­tients ex­pe­ri­enc­ing hos­pi­tal­iza­tions or hos­pi­tal­iza­tions and deaths.”

That Brazil­ian tri­al with al­most 1,500 en­rollees met its pri­ma­ry end­point, al­though the FDA took is­sue with the fact that the “re­sults were pri­mar­i­ly dri­ven by a re­duc­tion in the emer­gency de­part­ment vis­its last­ing greater than 6 hours, and there are un­cer­tain­ties about the as­sess­ment of this end­point and whether the 6-hour time­point rep­re­sents a clin­i­cal­ly mean­ing­ful thresh­old.”

An­oth­er, dif­fer­ent tri­al and small­er sets of re­al-world da­ta stud­ies were ham­pered by de­sign lim­i­ta­tions, end­point se­lec­tion ques­tions, and a lack of ran­dom­iza­tion, the FDA said. “Two ad­di­tion­al tri­als, STOP COVID 2 (a tri­al that was sev­er­al times larg­er than the STOP COVID tri­al) and COVID-OUT failed to demon­strate a ben­e­fit with flu­vox­am­ine in adults with mild Covid-19 in the out­pa­tient set­ting, and both were ter­mi­nat­ed ear­ly for fu­til­i­ty.”

The FDA al­so sought to ad­dress the ra­tio­nale by which a flu­vox­am­ine EUA would be sub­mit­ted for Covid-19, ex­plain­ing how it was based on murine sep­sis and lipopolysac­cha­ride chal­lenge mod­els in which flu­vox­am­ine was found to bind to the sig­ma-1 re­cep­tor on im­mune cells, re­duc­ing the pro­duc­tion of in­flam­ma­to­ry cy­tokines.

But with lim­it­ed in vit­ro and in vi­vo da­ta to sup­port the pro­posed MOA of flu­vox­am­ine in Covid-19, FDA said it would have to re­ject the app.

The re­jec­tion comes as the NIH had pre­vi­ous­ly said there was in­suf­fi­cient ev­i­dence to rec­om­mend ei­ther for or against the use of flu­vox­am­ine for the treat­ment of Covid.

Boul­ware, who sub­mit­ted the app, took is­sue with the FDA’s de­ci­sion, re­spond­ing to the re­jec­tion with a let­ter shared with End­points News, which high­lights the FDA’s in­con­sis­tent use of the term hos­pi­tal­iza­tion.

“FDA should eval­u­ate clin­i­cal tri­als us­ing the same end­point de­f­i­n­i­tions for gener­ic drugs as for big phar­ma,” the let­ter says. “The de­lib­er­ate cre­ation of two-tiered sys­tem is in­ap­pro­pri­ate.”

While Boul­ware wrote that he con­curred “that flu­vox­am­ine has a very mod­est ef­fi­ca­cy which is about the same ef­fi­ca­cy as [Mer­ck and Ridge­back’s] mol­nupi­ravir. The mol­nupi­ravir da­ta are sim­i­lar­ly weak, and the UK Panoram­ic tri­al will pro­vide more de­fin­i­tive ev­i­dence.”

But he al­so not­ed that as a clin­i­cal tri­al­ist,

there re­mains a need for greater two-way com­mu­ni­ca­tion be­tween FDA and the re­search com­mu­ni­ty. FDA’s cur­rent guid­ance for tri­al end­points for out­pa­tient ear­ly treat­ment of Covid-19 pre­tends as if it is cir­ca 2020. A med­ica­tion is ben­e­fi­cial for many rea­sons, in­clud­ing short­en­ing du­ra­tion of ill­ness or pre­vent­ing pro­gres­sion to se­vere Covid-19. Pro­gres­sion to hos­pi­tal­iza­tion/death is sub­stan­tial­ly low­er in vac­ci­nat­ed pop­u­la­tions and/or those with pri­or in­fec­tion. This is no longer a re­al­is­tic tri­al pri­ma­ry end­point.

The Senate won’t return from its summer recess until Sept. 6, but when it does, it officially has 18 business days to finalize the reauthorization of the FDA user fee programs for the next 5 years, or else thousands of drug and biologics reviewers will be laid off and PDUFA dates will vanish in the interim.

FDA commissioner Rob Califf recently sent agency staff a memo explaining how, “Our latest estimates are that we have carryover for PDUFA [Prescription Drug User Fee Act], the user fee funding program that will run out of funding first, to cover only about 5 weeks into the next fiscal year.”

Regulators didn’t keep AstraZeneca and Daiichi Sankyo waiting long at all for their latest Enhertu approval.

The partners pulled a win on Friday in HER2-low breast cancer patients who’ve already failed on chemotherapy, less than two weeks after its supplemental BLA was accepted. While this isn’t the FDA’s fastest approval — Bristol Myers Squibb won an OK for its blockbuster checkpoint inhibitor Opdivo in just five days back in March — it comes well ahead of Enhertu’s original Q4 PDUFA date.

Months after Novavax celebrated its first profitable quarter as a commercial company, the Gaithersburg, MD-based company is back in the red.

Sales for Novavax’s Covid-19 vaccine slipped to $55 million last quarter, down from $586 million in Q1, CEO Stanley Erck revealed on Monday after market close. The company’s stock $NVAX plummeted more than 32% in after-hours trading.

Upon kicking off the call with analysts and investors, Erck addressed the elephant in the room:

Back in 2018, Swiss drugmaker Ferring Pharmaceuticals made a big bet on Minnesota-based Rebiotix, buying up the company for its experimental poop-based drug implant to treat an infection caused by C. difficile, a potentially dangerous bacteria, in a new way.

Four years later, Ferring’s fecal microbiota transplant, dubbed RBX2660 or Rebyota, will face the FDA’s adcomm of outside vaccine experts on Sept. 22, debating whether the agency should license the transplant as a treatment for adults following antibiotic treatment for recurrent C. difficile infection.