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.

In a stun­ning set­back, Amarin los­es big patent fight over Vas­cepa IP. And its high-fly­ing stock crash­es to earth

Amarin’s shares $AMRN were blitzed Monday evening, losing billions in value as reports spread that the company had lost its high-profile effort to keep its Vascepa patents protected from generic drugmakers.

Amarin had been fighting to keep key patents under lock and key — and away from generic rivals — for another 10 years, but District Court Judge Miranda Du in Las Vegas ruled against the biotech. She ruled that:
(A)ll the Asserted Claims are invalid as obvious under 35 U.S.C.§ 103. Thus, the Court finds in favor of Defendants on Plaintiff’s remaining infringementclaim, and in their favor on their counterclaims asserting the invalidity of the AssertedClaims under 35 U.S.C. § 103.

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UP­DAT­ED: Have a new drug that promis­es to fight Covid-19? The FDA promis­es fast ac­tion but some de­vel­op­ers aren't hap­py

After providing an emergency approval to use malaria drugs against coronavirus with little actual evidence of their efficacy or safety in that setting, the FDA has already proven that it has set aside the gold standard when it comes to the pandemic. And now regulators have spelled out a new approach to speeding development that promises immediate responses in no uncertain terms — promising a program offering the ultimate high-speed pathway to Covid-19 drug approvals.

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The race to de­vel­op Covid-19 drugs and vac­cines is on — here’s what’s hap­pen­ing in the UK

Weeks away from the results of ongoing US and China trials testing its experimental antiviral remdesivir, Gilead is going to trial the failed Ebola drug in a small group of coronavirus patients in England and Scotland. The United Kingdom is also home to a range of other therapeutic efforts, as the pandemic rages on across the globe.

On Tuesday, Southampton, UK-based startup Synairgen kicked off a mid-stage placebo-controlled study testing its experimental drug, SNG001 — an inhaled formulation of interferon-beta-1a — that has previously shown to be safe and effective in improving lung function in asthma patients with a respiratory viral infection in a pair of Phase II trials.

‘There was a grow­ing weari­ness’: Rush­ing against a pan­dem­ic clock, As­pen Neu­ro­sciences se­cures $70M Se­ries A

Just before Christmastime, Howard Federoff got a tip from Washington: There was a new virus in China. And this one could be bad.

News report of the virus had not yet appeared. Federoff, a neuroscientist, was briefed because years before, he was vetted as part of a group — he didn’t give a name for the group — to consult for the US government on emerging scientific issues. His day job, though, was CEO of Aspen Neurosciences, a Parkinson’s cell therapy startup that days before had come out of stealth mode and gave word to investors they were hoping to raise $70 million. That, Federoff realized, would be difficult if a pandemic shut down the global economy.

FDA puts pe­di­atric aGVHD drug on pri­or­i­ty re­view lane — will they go vir­tu­al with the ad­comm?

Despite worries about regulatory delays due to new work arrangements under Covid-19, the FDA appears intent to go full speed ahead with its everyday work, not only granting priority review to a stem cell therapy for acute graft versus host disease but also plotting an advisory committee meeting for it.

With a PDUFA date of September 30, the journey of the drug — remestemcel-L, or Ryoncil — could shed light on the agency’s capacity to facilitate drug development unrelated to Covid-19.

Once fu­ri­ous over No­var­tis’ da­ta ma­nip­u­la­tion scan­dal, the FDA now says it’s noth­ing they need to take ac­tion on

Back in the BP era — Before Pandemic — the FDA ripped Novartis for its decision to keep the agency in the dark about manipulated data used in its application for Zolgensma while its marketing application for the gene therapy was under review.

Civil and criminal sanctions were being discussed, the agency noted in a rare broadside at one of the world’s largest pharma companies. Notable lawmakers cheered the angry regulators on, urging the FDA to make an example of Novartis, which fielded Zolgensma at $2.1 million — the current record for a one-off therapy.

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Covid-19 roundup: GSK, Am­gen tai­lor R&D work to fit the coro­n­avirus age; Doud­na's ge­nomics crew launch­es di­ag­nos­tic lab

You can add Amgen and GSK to the list of deep-pocket drug R&D players who are tailoring their pipeline work to fit a new age of coronavirus.

Following in the footsteps of a lineup of big players like Eli Lilly — which has suspended patient recruitment for drug studies — Amgen and GSK have opted to take a more tailored approach. Amgen is intent on circling the wagons around key studies that are already fully enrolled, and GSK has the red light on new studies while the pandemic plays out.

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Covid-19 roundup: Trump push­es his new fa­vorite, untest­ed drug; CRISPR out­lines crip­pling im­pact of Covid-19

President Trump has a new favorite Covid-19 drug.

After a conversation with Japanese Prime Minister Shinzo Abe, Politico reports, the president is pressuring the FDA to issue emergency use authorization for favipiravir, a flu drug that showed glimpses of success in China but remains unproven and carries a list of worrying side effects. The push comes after a week-plus in which the White House touted a potentially effective but unproven malaria medication despite the concerns of scientific advisors such as NIAID director Anthony Fauci. And Trump ally Rudy Giuliani has been talking up unproven cell therapy efforts on Twitter.

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ITeos nabs $125M as they prep Keytru­da com­bi­na­tion tri­al — if Covid-19 will let them

For iTeos, it turned out, $75 million could only last so long.

Two years after announcing their eye-catching Series B raise, the Belgian biotech is back with an even larger Series B-2: $125 million.

The now $175 million financing – $25 million of the first B round is considered part of the second – illustrates the vast capital available for those with promising new immuno-oncology compounds, particularly those that might be used in combination with existing therapies. In December, iTeos announced a collaboration with Merck to test its lead compound with Keytruda this year. The proceeds will push forward that trial and help fund the ongoing Phase I/II trials for that compound, EOS-850, and a second one, EOS-448.

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