J&J racks up a fresh set of pos­i­tive piv­otal da­ta for de­pres­sion drug es­ke­t­a­mine — but ques­tions linger on safe­ty

J&J has tak­en an­oth­er big step for­ward in its quest to bring home a block­buster ap­proval for its nasal spray for­mu­la­tion of ke­t­a­mine as a new rem­e­dy for ma­jor de­pres­sion.

Just weeks af­ter the phar­ma gi­ant re­port­ed that es­ke­t­a­mine had es­sen­tial­ly aced short-term piv­otal stud­ies, re­searchers are back with ev­i­dence of its long-term ef­fi­ca­cy. But they will like­ly face care­ful scruti­ny over the sub­stan­tial side ef­fects spurred by the ther­a­py, in­clud­ing a set of se­ri­ous ad­verse events re­port­ed in the lengthy safe­ty study.

The ef­fi­ca­cy study fo­cused on 705 treat­ment-re­sis­tant pa­tients re­cruit­ed out of its Phase III pro­gram who were sta­ble af­ter 16 weeks of ther­a­py with es­ke­t­a­mine and an oral an­ti-de­pres­sant. Fol­low­ing an­oth­er stretch of treat­ment, the es­ke­t­a­mine com­bo proved sig­nif­i­cant­ly more ef­fec­tive in pre­vent­ing a re­lapse than a place­bo spray plus oral de­pres­sion drug.

About one in four (26.7%) of the sta­ble re­mit­ters in the es­ke­t­a­mine arm ex­pe­ri­enced a re­lapse com­pared to 45.3% of the place­bo group (p=0.003) — a strong­ly pos­i­tive out­come. It’s par­tic­u­lar­ly sig­nif­i­cant that the re­searchers were able to track longterm re­spons­es for a drug known for its ephemer­al im­pact.

The safe­ty da­ta are a lit­tle more com­plex. As seen ear­li­er, and com­plete­ly ex­pect­ed, there was a high rate of dis­so­ci­a­tion — 22.4%. That un­der­scores why J&J plans to have the drug in­fused in a clin­ic, with an ob­ser­va­tion pe­ri­od to make sure pa­tients were be­hav­ing nor­mal­ly be­fore they leave.

Es­ke­t­a­mine is a low dose of ke­t­a­mine, a par­ty drug and horse tran­quil­iz­er that’s of­ten abused. J&J here is try­ing to nav­i­gate its way through Phase III with an ac­cept­able for­mu­la­tion for a tough pa­tient pop­u­la­tion in a field known for wide­spread fail­ure.

The safe­ty study was open la­bel, with pa­tients aware they were get­ting the drug. Re­searchers re­port­ed:

Fifty-five (6.9%) pa­tients ex­pe­ri­enced 68 se­ri­ous treat­ment-emer­gent ad­verse events. Of these, five se­ri­ous treat­ment-emer­gent ad­verse events from four sub­jects were as­sessed by the in­ves­ti­ga­tor as es­ke­t­a­mine nasal spray-re­lat­ed. There were two deaths which the in­ves­ti­ga­tor de­ter­mined to be un­re­lat­ed to es­ke­t­a­mine nasal spray or oral an­ti­de­pres­sant use. Lab­o­ra­to­ry tests, phys­i­cal ex­am­i­na­tion, and nasal tol­er­a­bil­i­ty re­vealed no trends of clin­i­cal con­cern in pa­tients treat­ed with es­ke­t­a­mine nasal spray for up to 52 weeks. No clin­i­cal­ly mean­ing­ful changes in cog­ni­tion were found. No cas­es of in­ter­sti­tial or ul­cer­a­tive cys­ti­tis were re­port­ed.

I asked a com­pa­ny rep what the five se­ri­ous ad­verse events were, as it could be rel­e­vant to a reg­u­la­to­ry re­view. Her re­sponse: de­pres­sion, delir­i­um, anx­i­ety and delu­sion, sui­ci­dal ideation and sui­cide at­tempt.

J&J has list­ed es­ke­t­a­mine as one of its top late-stage de­vel­op­ment pro­grams, prep­ping ap­pli­ca­tions for both sides of the At­lantic. They’re not home free yet, but in de­pres­sion uni­form safe­ty and ef­fi­ca­cy is un­heard of, with reg­u­la­tors will­ing to bal­ance the risks with the ben­e­fits for a tough group to treat.

On that score, J&J is well ahead of the game.

Biotech and Big Phar­ma: A blue­print for a suc­cess­ful part­ner­ship

Strategic partnerships have long been an important contributor to how drugs are discovered and developed. For decades, big pharma companies have been forming alliances with biotech innovators to increase R&D productivity, expand geographical reach and better manage late-stage commercialization costs.

Noël Brown, Managing Director and Head of Biotechnology Investment Banking, and Greg Wiederrecht, Ph.D., Managing Director in the Global Healthcare Investment Banking Group at RBC Capital Markets, are no strangers to the importance of these tie-ups. Noël has over 20 years of investment banking experience in the industry. Before moving to the banking world in 2015, Greg was the Vice President and Head of External Scientific Affairs (ESA) at Merck, where he was responsible for the scientific assessment of strategic partnership opportunities worldwide.

No­var­tis' sec­ond at­tempt to repli­cate a stun­ning can­cer re­sult falls flat

Novartis’ hopes of turning one of the most surprising trial data points of the last decade into a lung cancer drug has taken another setback.

The Swiss pharma announced Monday that its IL-1 inhibitor canakinumab did not significantly extend the lives or slow the disease progression of patients with previously untreated locally advanced or metastatic non-small cell lung cancer when compared to standard of-care alone.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,800+ biopharma pros reading Endpoints daily — and it's free.

Credit: Shutterstock

How Chi­na turned the ta­bles on bio­phar­ma's glob­al deal­mak­ing

Fenlai Tan still gets chills thinking about the darkest day of his life.

Three out of eight lung cancer patients who received a tyrosine kinase inhibitor developed by his company, Betta Pharma, died in the span of a month. Tan, the chief medical officer, was summoned to Peking Union Medical College Hospital, where the head of the clinical trial department told him that the trial investigators would be conducting an autopsy to see if the patients had died of the disease — they were all very sick by the time they enrolled — or of interstitial lung disease, a deadly side effect tied to the TKI class that’s been reported in Japan.

An­gion's or­gan dam­age drug strikes out again, this time in high-risk kid­ney trans­plant pa­tients

After flopping a test in Covid-19 earlier this year, Angion’s lead organ damage drug has now hit the skids again in kidney transplant patients.

Angion and partner Vifor Pharma’s ANG-3777 failed to beat out placebo in terms of improving eGFR, a measure of kidney function, in patients who had received a deceased donor kidney transplant and were at high risk of developing what is known as delayed graft function, according to Phase III results released Tuesday.

An image of Alzheimer's brain tissue. The red show gingipains, a protein from P. gingivalis, intermixing with neurons (yellow) and glial cells (green)

An Alzheimer's dark­horse fails its first big tri­al, but of­fers hope for a long-over­looked hy­poth­e­sis

Three years ago, Cortexyme emerged out of obscurity with some big-name backers and an unorthodox approach to treating Alzheimer’s.

They moved their drug into a pivotal study the next year, offering one of the first major tests for a hypothesis that has fluttered on the outskirts of Alzheimer’s research for decades: that, in many cases, the disease is driven by infectious agents — the havoc they wreak in the brain and the inflammation the body uses to try to fend them off. And that quashing the infection could slow patients’ cognitive decline.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,800+ biopharma pros reading Endpoints daily — and it's free.

No­var­tis dumps AveX­is pro­gram for Rett syn­drome af­ter fail­ing re­peat round of pre­clin­i­cal test­ing

Say goodbye to AVXS-201.

The Rett syndrome gene therapy drug made by AveXis — the biotech that was bought, kept separate, then renamed and finally absorbed by Novartis into its R&D division — has been dropped by the biopharma.

In Novartis’ third quarter financial report, the pharma had found that preclinical data did not support development of the gene therapy into IND-enabling trials and beyond. The announcement comes a year after Novartis told the Rett Society how excited it was by the drug — and its potential benefits and uses.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,800+ biopharma pros reading Endpoints daily — and it's free.

Peter Nell, Mammoth Biosciences CBO

UP­DAT­ED: Jen­nifer Doud­na spin­out inks a Mam­moth CRISPR deal with Ver­tex worth near­ly $700M

When a company gets its start in gene editing pioneer Jennifer Doudna’s lab, it’s bound to make headlines. But three years in, the fanfare still hasn’t died down for Mammoth Biosciences. Now, the Brisbane, CA-based company is cheering on its first major R&D pact.

Mammoth unveiled a nearly $700 million deal with Vertex on Tuesday morning, good for the development of in vivo gene therapies for two mystery diseases. The stars of the show are Mammoth’s ultra-small CRISPR systems, including two Cas enzymes licensed from Doudna’s lab over the past couple years, Cas14 and Casɸ.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,800+ biopharma pros reading Endpoints daily — and it's free.

FDA is much worse than its reg­u­la­to­ry peers at proac­tive­ly dis­clos­ing da­ta, re­searchers find

The European Medicines Agency and Health Canada continue to outpace the FDA when it comes to proactively releasing data on drugs and biologics the agency has reviewed, leading to further questions of why the American agency can’t be more transparent.

In a study published recently in the Journal of Law, Medicine, & Ethics, Yale and other academic lawyers and researchers found that between 2016 and April 2021, the EMA proactively released data for 123 unique medical products, while Health Canada proactively released data for 73 unique medical products between 2019 and April 2021. What’s more, the EMA and Health Canada didn’t proactively release the same data on the same drugs. In stark contrast, the FDA in 2018 only proactively disclosed data supporting one drug that was approved that year.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 120,800+ biopharma pros reading Endpoints daily — and it's free.

NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.