With hits and miss­es in first piv­otal tri­als, J&J con­fi­dent­ly maps a path to the FDA with its ma­jor de­pres­sion med es­ke­t­a­mine

J&J re­searchers rolled out da­ta from the first two piv­otal tri­als of their an­ti-de­pres­sion drug es­ke­t­a­mine to­day, blaz­ing a trail that they say leads straight to an FDA fil­ing in a mat­ter of months with a ground­break­ing ap­proach to treat­ing ma­jor de­pres­sion.

The da­ta are mixed, with some hits and miss­es, as you’ll see fur­ther be­low as I set out the da­ta points. But there are some im­por­tant caveats to note about the num­bers for a low-dose, in­tranasal for­mu­la­tion of a pow­er­ful anes­thet­ic and fre­quent­ly abused par­ty drug — bet­ter known as Spe­cial K — which will in­vite a very care­ful ex­am­i­na­tion by reg­u­la­tors.

First, and fore­most, the FDA doesn’t re­quire per­fec­tion in de­pres­sion stud­ies, a field where a high place­bo re­sponse is a vir­tu­al giv­en. Be­cause these were hard-to-treat pa­tients, they couldn’t re­serve sole­ly a place­bo for the con­trol arm of the stud­ies. One group re­ceived es­ke­t­a­mine in a nasal spray with an ac­tive de­pres­sion drug while the con­trol arm was giv­en an ac­tive de­pres­sion drug — invit­ing a high re­sponse in the con­trol group, which they got.

Nev­er­the­less, they still beat the con­trol group re­sponse in the first key Phase III. And the in­ves­ti­ga­tors say that stud­ies read­ing out in the next few months will com­plete a pic­ture of pos­i­tive re­sults that reg­u­la­tors will not be able to re­ject for these pa­tients.

“We be­lieve with these stud­ies that we’re go­ing to meet that hur­dle,” says David Hough, Janssen’s clin­i­cal tri­al leader for es­ke­t­a­mine.


The first study among pa­tients with hard-to-treat ma­jor de­pres­sion hit a clear­ly sta­tis­ti­cal­ly sig­nif­i­cant re­sult for the com­mon­ly used Mont­gomery-Ås­berg De­pres­sion Rat­ing Scale, or MADRS. And a low dose ver­sion used in el­der­ly pa­tients missed sta­tis­ti­cal sig­nif­i­cance — they hit a p-val­ue of 0.029 in a tri­al that set the bar for sig­nif­i­cance at 0.025.

The first study al­so missed a key sec­ondary: on­set of clin­i­cal ef­fect in 24 hours main­tained through 28 days in a rel­a­tive­ly short tri­al. And be­cause of that miss they couldn’t for­mal­ly present da­ta on the next two sec­on­daries.

Two oth­er key mea­sures scored for the es­ke­t­a­mine com­bo.

  • There was a 69.3% re­sponse rate in the es­ke­t­a­mine/de­pres­sion drug com­bo group ver­sus a (very high) 52% in the con­trol group at 28 days.
  • The re­mis­sion rate at day 28 was 52.5% for the es­ke­t­a­mine com­bo and 31% for the es­ke­t­a­mine and place­bo nasal spray group.

“This is not gar­den va­ri­ety de­pres­sion,” says Hough. The pa­tients in these stud­ies had tried and failed any­where from two to 5 dif­fer­ent de­pres­sion meds.

Among the side ef­fects of the es­ke­t­a­mine com­bi­na­tion, re­searchers found that some pa­tients suf­fered from dis­so­ci­a­tion, not un­ex­pect­ed in a drug that at high dos­es is some­times used to in­duce schiz­o­phrenic be­hav­ior in clin­i­cal tri­als. J&J’s ap­proach to that will be to pro­vide this drug on­ly un­der care­ful su­per­vi­sion in a clin­i­cal set­ting. That might com­pli­cate mar­ket­ing, if ap­proved, but in a time of wide­spread opi­oid abuse, J&J knows there will be care­ful clin­i­cal re­stric­tions on dis­tri­b­u­tion.

If ap­proved, Hough says the plan would be to use the drug twice a week ini­tial­ly for 4 weeks and then start low­er­ing the fre­quen­cy un­til they get the right main­te­nance lev­el.

If they can win here, they add, this will be the first new drug for treat­ment-re­sis­tant cas­es of ma­jor de­pres­sion in decades.

“We were very pleased,” says Hough, who’s prep­ping the roll­out on more promis­ing da­ta from three more stud­ies.

Over the years a host of aca­d­e­mics have re­peat­ed­ly seen ke­t­a­mine score high for swift if tem­po­rary treat­ment of de­pres­sion and sui­ci­dal think­ing. But its pow­er­ful ef­fects over­all pre­vent its use. That’s what set J&J down this path with a low-dose ver­sion of the drug, while Al­ler­gan and oth­ers are test­ing NM­DA drugs that mim­ic par­tic­u­lar as­pects of the par­ty drug, look­ing for a nar­row hit on de­pres­sion with­out the il­lic­it side ef­fects.

MedTech clinical trials require a unique regulatory and study design approach and so engaging a highly experienced CRO to ensure compliance and accurate data across all stages is critical to development milestones.

In­no­v­a­tive MedTech De­mands Spe­cial­ist Clin­i­cal Tri­al Reg­u­la­to­ry Af­fairs and De­sign

Avance Clinical is the Australian CRO for international biotechs providing world-class clinical research services with FDA-accepted data across all phases. With Avance Clinical, biotech companies can leverage Australia’s supportive clinical trials environment which includes no IND requirement plus a 43.5% Government incentive rebate on clinical spend. The CRO has been delivering clinical drug development services for international biotechs for FDA and EMA regulatory approval for the past 24 years. The company has been recognized for the past two consecutive years with the prestigious Frost & Sullivan CRO Best Practices Award and a finalist in Informa Pharma’s Best CRO award for 2022.

Gold for adults, sil­ver for in­fants: Pfiz­er's Pre­vnar 2.0 head­ed to FDA months af­ter Mer­ck­'s green light

Pfizer was first to the finish line for the next-gen pneumococcal vaccine in adults, but Merck beat its rival with a jab for children in June.

Now, two months after Merck’s 15-valent Vaxneuvance won the FDA stamp of approval for kids, Pfizer is out with some late-stage data on its 20-valent shot for infants.

Known as Prevnar 20 for adults, Pfizer’s 20vPnC will head to the FDA by the end of this year for an approval request in infants, the Big Pharma said Friday morning. Discussions with the FDA will occur first and more late-stage pediatric trials are expected to read out soon, informing the regulatory pathway in other countries and regions.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.

His­toric drug pric­ing re­forms pass; Pfiz­er ac­quires GBT; The long search for non-opi­oid pain drugs; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

The Endpoints Weekly has officially crossed the 60,000 mark on subscribers — thanks to all of your support. As the editorial team grows, we’ve been able to do a lot more, with many of those on display this week. Be sure to check out Lei Lei Wu’s deep dive on pain R&D. If you missed it, you may also rewatch her companion panel here.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.

No­var­tis re­ports two pa­tient deaths af­ter treat­ment with Zol­gens­ma

Two children with spinal muscular atrophy have died after receiving Novartis’ Zolgensma, a gene therapy designed as a one-time treatment for the rare fatal disease.

The deaths, which resulted from acute liver failure, occurred in Russia and Kazakhstan, Novartis confirmed in a statement to Endpoints News. Having notified health authorities across all the markets where Zolgensma is available, it will update the drug label “to specify that fatal acute liver failure has been reported,” a spokesperson wrote.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.

House pass­es his­toric drug pric­ing re­forms, lin­ing up decades-in-the-mak­ing win for Biden and De­moc­rats

The US House of Representatives today voted along party lines (all Dems voted for it), 220-207 to pass new, wide-ranging legislation that will allow Medicare drug price negotiations for the first time ever, and cap seniors’ drug expenses to $2,000 per year and seniors’ insulin costs at $35 per month.

Setting up a major victory for President Joe Biden, representatives returned from their summer recess to pass the Inflation Reduction Act, even as many noted the bill would only modestly reduce inflation.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.

Senate Finance Committee Chair Ron Wyden (D-OR) (Francis Chung/E&E News/POLITICO via AP Images)

Sen­ate Fi­nance chair con­tin­ues his in­ves­ti­ga­tion in­to phar­ma tax­es with re­quests for Am­gen

Amgen is the latest pharma company to appear on the radar of Senate Finance Committee Chair Ron Wyden (D-OR), who is investigating the way pharma companies are using subsidiaries in low- or zero-tax countries to lower their tax bills.

Like its peers Merck, AbbVie and Bristol Myers Squibb, Wyden notes how Amgen uses its Puerto Rico operations to consistently pay tax rates that are substantially lower than the U.S. corporate tax rate of 21%, with an effective tax rate of 10.7% in 2020 and 12.1% in 2021.

FDA ap­proves sec­ond in­di­ca­tion for As­traZeneca and Dai­ichi's En­her­tu in less than a week

AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu scored its second approval in less than a week, this time for a subset of lung cancer patients.

Enhertu received accelerated approval on Thursday to treat adults with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, and who have already received a prior systemic therapy.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.

J&J to re­move talc prod­ucts from shelves world­wide, re­plac­ing with corn­starch-based port­fo­lio

After controversially spinning out its talc liabilities and filing for bankruptcy in an attempt to settle 38,000 lawsuits, Johnson & Johnson is now changing up the formula for its baby powder products.

J&J is beginning the transition to an all cornstarch-based baby powder portfolio, the pharma giant announced on Thursday — just months after a federal judge ruled in favor of its “Texas two-step” bankruptcy to settle allegations that its talc products contained asbestos and caused cancer. An appeals court has since agreed to revisit that case.

CSL is gathering its four business units under a unified brand identity strategy (Credit: CSL company site)

CSL brings Se­qirus, Vi­for un­der par­ent um­brel­la brand in iden­ti­ty re­vamp

CSL is gathering its brands under the family name umbrella, renaming its vaccine and newly acquired nephrology specialty businesses with the parent initials.

CSL Seqirus and CSL Vifor join CSL Plasma and CSL Behring as the four now uniformly branded business units of the global biopharma. The Seqirus vaccine division was formed in 2015 with the combination of bioCSL and its purchase of Novartis’ flu vaccine business. CSL picked up Vifor Pharma late last year in an $11.7 billion deal for the nephrology, iron deficiency and cardio-renal drug developer.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 147,700+ biopharma pros reading Endpoints daily — and it's free.