FDA ex­perts of­fer a big thumbs up for J&J’s flawed ap­pli­ca­tion for ke­t­a­mine-based de­pres­sion drug — but tri­al fail­ures, safe­ty ques­tions spur con­cerns

J&J may have a deeply flawed ap­pli­ca­tion for its new/old drug to treat ma­jor de­pres­sion, but the re­searchers who turned out to present the case for es­ke­t­a­mine en­coun­tered a re­cep­tive au­di­ence of FDA ex­perts on Tues­day. 

By a wide mar­gin — 14 yes, 2 no and 1 ab­sten­tion — the pan­el con­clud­ed that J&J had of­fered “sub­stan­tial ev­i­dence of the ef­fec­tive­ness of es­ke­t­a­mine,” an in­tranasal ver­sion of a pow­er­ful anes­thet­ic called ke­t­a­mine, bet­ter known in par­ty cir­cles as ‘Spe­cial K.’

The key safe­ty is­sue is the known link be­tween the long­time use of ke­t­a­mine and neu­ro­tox­i­c­i­ty. The re­searchers re­lied on pre­clin­i­cal dog and rat stud­ies to make their case — hard­ly the gold stan­dard on safe­ty da­ta. But the pan­el seemed con­tent that a long-term safe­ty study on a post­mar­ket­ing ba­sis would be enough to war­rant an OK now, with 15 vot­ing that J&J had suc­cess­ful­ly out­lined the safe­ty pro­file for an ini­tial ap­proval. And at least one of the au­thor­i­ties not­ed that cur­rent­ly used de­pres­sion drugs al­so have safe­ty is­sues with long­time use.

The mon­ey ques­tion:

Do the ben­e­fits out­weigh the risks? Yes: 14. No: 2. Ab­stain: 1.

J&J calls es­ke­t­a­mine — which they plan to mar­ket as Spra­va­to — the first drug with a new mech­a­nism of ac­tion in de­pres­sion for some 30 years. Of course, ke­t­a­mine has al­so been used off-la­bel for de­pres­sion for years. It’s an NM­DA drug, with ri­vals in the clin­ic from var­i­ous bio­phar­ma com­pa­nies, in­clud­ing Al­ler­gan.

“Ke­t­a­mine is a nasty drug,” not­ed pan­el mem­ber Steven Meisel, sys­tem di­rec­tor of med­ica­tion safe­ty at Fairview Health Ser­vices/Health­east Care Sys­tem. “It’s been around for 50 years….But ob­vi­ous­ly we’re us­ing low­er dos­es.” Meisel, though, was im­pressed by a sur­vey re­searchers com­plet­ed that high­light­ed just how much these pa­tients need­ed a new ther­a­py.

“You don’t take that pa­tient’s voice as of­ten as you should in this space.”

“The vast ma­jor­i­ty of these pa­tients will take the risks,” he added. “I think that’s very im­por­tant….”

Two of the stud­ies failed to meet the pri­ma­ry out­come, and that raised con­cerns. 

“What prece­dent is set when 2 of 3 short­er ef­fi­ca­cy stud­ies didn’t meet the pri­ma­ry end­point?” Meisel asked. “That’s some­thing the agency has to wres­tle with. “Do we set a prece­dent that may be hard to step back from.”

If the FDA goes ahead and of­fers a for­mal ap­proval, which looks in­creas­ing­ly like­ly in view of the neu­tral in­ter­nal re­view, they’ll be once again over­look­ing the agency’s gold stan­dard on 2 pos­i­tive, well con­trolled stud­ies. But that’s in­creas­ing­ly com­mon, es­pe­cial­ly un­der com­mis­sion­er Scott Got­tlieb.

J&J ex­pe­ri­enced sig­nif­i­cant fail­ures with this pro­gram, and has promis­ing da­ta from one late-stage study and a with­draw­al study, which the ex­perts and in­sid­ers seemed will­ing to ac­cept in lieu of a sec­ond well-con­trolled tri­al.

Es­ke­t­a­mine is one of J&J’s top late-stage drugs, which the phar­ma gi­ant be­lieves has block­buster mar­ket po­ten­tial. By all ap­pear­ances, they’ll soon be able to ex­plore just how big this drug can be.

Susan Galbraith, AstraZeneca EVP, oncology R&D, at EUBIO22 (Rachel Kiki for Endpoints News)

Up­dat­ed: As­traZeneca jumps deep­er in­to cell ther­a­py 2.0 space with $320M biotech M&A

Right from the start, the execs at Neogene had some lofty goals in mind when they decided to try their hand at a cell therapy that could tackle solid tumors.

Its founders have helped hone a new approach that would pack in multiple neoantigen targets to create a personalized TCR treatment that would not just make the leap from blood to solid tumors, but do it with durability. And they managed to make their way rapidly to the clinic, unveiling their first Phase I program for advanced tumors just last May.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Ei­sai’s ex­pand­ed Alzheimer’s da­ta leave open ques­tions about safe­ty and clin­i­cal ben­e­fit

Researchers still have key questions about Eisai’s investigational Alzheimer’s drug lecanemab following the publication of more Phase III data in the New England Journal of Medicine Tuesday night.

In the paper, which was released in conjunction with presentations at an Alzheimer’s conference, trial investigators write that a definition of clinical meaningfulness “has not been established.” And the relative lack of new information, following topline data unveiled in September, left experts asking for more — setting up a potential showdown to precisely define how big a difference the drug makes in patients’ lives.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Illustration: Assistant Editor Kathy Wong for Endpoints News

Twit­ter dis­ar­ray con­tin­ues as phar­ma ad­ver­tis­ers ex­tend paus­es and look around for op­tions, but keep tweet­ing

Pharma advertisers on Twitter are done — at least for now. Ad spending among the previous top spenders flattened even further last week, according to the latest data from ad tracker Pathmatics, amid ongoing turmoil after billionaire boss Elon Musk’s takeover now one month ago.

Among 18 top advertisers tracked for Endpoints News, only two are spending: GSK and Bayer. GSK spending for the full week through Sunday was minimal at just under $1,900. Meanwhile, German drugmaker Bayer remains the industry outlier upping its spending to $499,000 last week from $480,000 the previous week. Bayer’s spending also marks a big increase from a month ago and before the Musk takeover, when it spent $16,000 per week.

Endpoints Premium

Premium subscription required

Unlock this article along with other benefits by subscribing to one of our paid plans.

Vi­a­tris with­draws ac­cel­er­at­ed ap­proval for top­i­cal an­timi­cro­bial 24 years lat­er

After 24 years without confirming clinical benefit, the FDA announced Tuesday morning that Viatris (formed via Mylan and Pfizer’s Upjohn) has decided to withdraw a topical antimicrobial agent, Sulfamylon (mafenide acetate), after the company said conducting a confirmatory study was not feasible.

Sulfamylon first won FDA’s accelerated nod in 1998 as a topical burn treatment, with the FDA noting that last December, Mylan told the agency that it wasn’t running the trial.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 153,800+ biopharma pros reading Endpoints daily — and it's free.

Emily Leproust, Twist Bioscience CEO

Twist Bio­science’s 'fac­to­ry of the fu­ture' in Ore­gon could de­liv­er with com­pet­i­tive pric­ing, SVB Se­cu­ri­ties says

The synthetic DNA manufacturer Twist Bioscience has given a peek behind the curtain to several analysts into its “factory of the future” as well as insight into the cost structure, workflow and technology at the site.

The 110,000-square-foot manufacturing site in the city of Wilsonville, OR, just south of Portland, which was announced back in 2020, will double Twist’s production capacity and bring around 400 jobs to the area.

Paul Hudson, Sanofi CEO (Romuald Meigneux/Sipa via AP Images)

Sanofi and DN­Di aim to elim­i­nate sleep­ing sick­ness in Africa with promis­ing Ph II/III re­sults for new drug

The Drugs for Neglected Diseases initiative (DNDi) and Sanofi today said that their potential sleeping sickness treatment saw success rates of up to 95% from a Phase II/III study investigating the safety and efficacy of single-dose acoziborole.

The potentially transformative treatment for sleeping sickness would mainly be targeted at African countries, according to data published today in The Lancet Infectious Diseases medical journal. The clinical trial was led by DNDi and its partners in the Democratic Republic of the Congo (DRC) and Guinea, with the authors noting:

Digital render of CPI's Medicines Manufacturing Innovation Centre in Glasgow, Scotland (Image: uk-cpi.com)

CPI opens the doors to a new $100M+ man­u­fac­tur­ing fa­cil­i­ty in Scot­land

A manufacturing site that has received interest and investments from large pharma companies and the UK government is opening its doors in Scotland.

The manufacturer CPI (Centre for Process Innovation) has opened a new £88 million ($105 million) “Medicines Manufacturing Innovation Centre” in Glasgow, Scotland, to accelerate the development of manufacturing tech and solve longstanding challenges in medicine development and manufacturing.

Lex­i­con slams FDA over hear­ing de­nial fol­low­ing a CRL for its SGLT2 in­hibitor can­di­date

Lexicon Pharmaceutical is not giving up on its Type I diabetes candidate, despite FDA’s repeated rejections. This week the company laid out is argument again for a hearing on sotagliflozin in response to the FDA’s most recent denial.

The issue goes back to March 2019 when the FDA made very clear to Lexicon and its now departed partner Sanofi that it would not approve their application for a potential Type I diabetes drug because it does not appear to be safe.

Pro­tect­ing its megablock­buster, Janssen chal­lenges Am­gen's Ste­lara biosim­i­lar ahead of planned 2023 launch

Johnson & Johnson unit Janssen on Wednesday sued Amgen over the company’s proposed biosimilar to its megablockbuster Stelara (ustekinumab), after Amgen said it was ready to launch next May or as soon as the FDA signs off on it.

If Amgen carries through with that plan, Janssen told the Delaware district court that the Thousand Oaks, CA-based company will infringe on at least two Janssen patents.