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.

A New Fron­tier: The In­ner Ear

What happens when a successful biotech venture capitalist is unexpectedly diagnosed with a chronic, life-disrupting vertigo disorder? Innovation in neurotology.

That venture capitalist was Jay Lichter, Ph.D., and after learning there was no FDA-approved drug treatment for his condition, Ménière’s disease, he decided to create a company to bring drug development to neurotology. Otonomy was founded in 2008 and is dedicated to finding new drug treatments for the hugely underserved community living with balance and hearing disorders. Helping patients like Jay has been the driving force behind Otonomy, a company heading into a transformative 2020 with three clinical trial readouts: Phase 3 in Ménière’s disease, Phase 2 in tinnitus, and Phase 1/2 in hearing loss. These catalysts, together with others in the field, highlight the emerging opportunity in neurotology.
Otonomy is leading the way in neurotology
Neurotology, or the treatment of inner ear neurological disorders, is a large and untapped market for drug developers: one in eight individuals in the U.S. have moderate-to-severe hearing loss, tinnitus or vertigo disorders such as Ménière’s disease.1 With no FDA-approved drug treatments available for these conditions, the burden on patients—including social anxiety, lower quality of life, reduced work productivity, and higher rates of depression—can be significant.2, 3, 4

Joe Jimenez, Getty

Ex-No­var­tis CEO Joe Jimenez is tak­ing an­oth­er crack at open­ing a new chap­ter in his ca­reer — and that in­cludes a new board seat and a $250M start­up

Joe Jimenez is back.

The ex-CEO of Novartis has taken a board seat on Century Therapeutics, the Versant and Bayer-backed startup focused on coming up with a brand new twist on cell therapies for cancer — a field where Jimenez made his mark backing the first personalized CAR-T approved for use.

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Can we make the an­tibi­ot­ic mar­ket great again?

The standard for-profit model in drug development is straightforward. Spend millions, even billions, to develop a medicine from scratch. The return on investment (and ideally a tidy profit) comes via volume and/or price, depending on the disease. But the string of big pharma exits and slew of biotech bankruptcies indicate that the model is sorely flawed when it comes to antibiotics.

The industry players contributing to the arsenal of antimicrobials are fast dwindling, and the pipeline for new antibiotics is embarrassingly sparse, the WHO has warned. Drugmakers are enticed by greener pastures, compared to the long, arduous and expensive path to antibiotic approval that offers little financial gain as treatments are typically priced cheaply, and often lose potency over time as microbes grow resistant to them.

Top Har­vard chemist caught up in FBI’s 'T­hou­sand Tal­ents' drag­net, ac­cused of ly­ing about Chi­nese con­nec­tions, pay

The FBI’s probe into the alleged theft of R&D secrets by Chinese authorities has drawn Harvard’s top chemist into its net.

The agency accused Charles M. Lieber, who chairs the university’s chemistry and chemical biology department, with lying about his involvement in China’s Thousand Talents campaign, which was established as a way of drawing in innovators from around the world. And the scientist, 60, was charged with making false statements about his ties to China.

The US attorneys office in Boston also announced charges against two Chinese nationals for helping the Chinese government.

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Eye­ing a trio of tri­al ini­ti­a­tions, Jim Wilson's gene ther­a­py start­up woos Bruce Gold­smith from Deer­field as CEO

Passage Bio — Jim Wilson’s self-described “legacy company” — has wooed a seasoned biotech executive to steer the clinical entry of its first three gene therapy programs.

Bruce Goldsmith jumps to the helm of Passage after a brief CEO stint at Civetta, a cancer-focused startup he helped launch while a venture partner at Deerfield. He takes over from OrbiMed partner and interim chief Stephen Squinto, who will now lead the R&D team.

The FTC and New York state ac­cuse Mar­tin Shkre­li of run­ning a drug mo­nop­oly. They plan to squash it — and per­ma­nent­ly ex­ile him

Pharma bro Martin Shkreli was jailed, publicly pilloried and forced to confront some lawmakers in Washington riled by his move to take an old generic and move the price from $17.50 per pill to $750. But through 4 years of controversy and public revulsion, his company never backed away from the price — left uncontrolled by a laissez faire federal policy on a drug’s cost.

Now the FTC and the state of New York plan to pry his fingers off the drug once and for all and open it up to some cheap competition. And their lawsuit is asking that Shkreli — with several years left on his prison sentence — be banned permanently from the pharma industry.

UP­DAT­ED: Ac­celeron res­ur­rects block­buster hopes for so­tater­cept with pos­i­tive PhII — and shares rock­et up

Acceleron $XLRN says that its first major trial readout of 2020 is a success.

In a Phase II study of 106 patients with pulmonary arterial hypertension (PAH), Acceleron’s experimental drug sotatercept hit its primary endpoint: a significant reduction in pulmonary vascular resistance. The drug also met three different secondary endpoints, including the 6-minute walking test.

“We’re thrilled to report such positive topline results from the PULSAR trial,” Acceleron CEO Habib Dable said in a statement. The company said in a conference call they plan on discussing a Phase III trial design with regulators.

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Short at­tack­er Sahm Ad­ran­gi draws crosshairs over a fa­vorite of Sanofi’s new CEO — with PhII da­ta loom­ing

Sahm Adrang Kerrisdale

Kerrisdale chief Sahm Adrangi took a lengthy break from his series of biotech short attacks after his chief analyst in the field pulled up stakes and went solo. But he’s making a return to drug development this morning, drawing crosshairs over a company that’s one of new Sanofi CEO Paul Hudson’s favorite collaborators.

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Amber Saltzman (Ohana)

Flag­ship's first ven­ture of 2020 is out, and it's all about sperm

A couple years ago, Amber Salzman got a call as she was returning East full-time after a two-year stint running a gene therapy company in California.

It was from someone at Flagship Pioneering, the deep-pocketed biotech venture firm. They had a new company with a new way of thinking about sperm. It had been incubating for over a year, and now they wanted her to run it.

“It exactly fit,” Salzman told Endpoints News. “I just thought I had to do something.”