Un­per­suad­ed by the da­ta, FDA re­jects cheap, gener­ic SS­RI as a Covid-19 drug

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.

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

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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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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.

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.

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.

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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Isao Teshirogi, Shionogi president and CEO (Kyodo via AP Images)

Sh­ionogi's Covid an­tivi­ral lands first ap­proval in Japan's new emer­gency ap­proval path­way

Japanese regulators on Tuesday signed off on Shionogi’s homegrown antiviral for Covid-19, known as Xocova (ensitrelvir), making it the first approval under Japan’s emergency regulatory approval system.

The emergency approval, following a back-and-forth with regulators since last February, is based on a safety profile with more than 2,000 patients who have accessed the pill, and clinical symptomatic efficacy for five typical Omicron-related symptoms (primary endpoint) and antiviral efficacy (key secondary endpoint) in patients with mild to moderate SARS-CoV-2 infection, regardless of risk factors or vaccination status, and during the Omicron-dominant phase of the pandemic.

Stanley Erck, Novavax CEO (Andrew Harnik/AP Images)

No­vavax pulls out of Covid-19 vac­cine al­liance with Gavi

Novavax is pulling out of its Covid-19 vaccine deal with Gavi, the Vaccine Alliance, a global partnership tasked with ensuring vaccine access in lower-income countries, following an alleged contract violation.

The Maryland-based company claimed on Friday that Gavi failed to purchase at least 350 million doses of its protein-based vaccine Nuvaxovid by the end of the year, per an advanced purchase agreement. Gavi, the World Health Organization and the Coalition for Epidemic Preparedness Innovations (CEPI) are co-leaders of COVAX, an effort to ensure that all participating countries, regardless of income levels, have access to vaccines.

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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