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.

2019 Trin­i­ty Drug In­dex Eval­u­ates Ac­tu­al Com­mer­cial Per­for­mance of Nov­el Drugs Ap­proved in 2016

Fewer Approvals, but Neurology Rivals Oncology and Sees Major Innovations

This report, the fourth in our Trinity Drug Index series, outlines key themes and emerging trends in the industry as we progress towards a new world of targeted and innovative products. It provides a comprehensive evaluation of the performance of novel drugs approved by the FDA in 2016, scoring each on its commercial performance, therapeutic value, and R&D investment (Table 1: Drug ranking – Ratings on a 1-5 scale).

How to cap­i­talise on a lean launch

For start-up biotechnology companies and resource stretched pharmaceutical organisations, launching a novel product can be challenging. Lean teams can make setting a launch strategy and achieving your commercial goals seem like a colossal undertaking, but can these barriers be transformed into opportunities that work to your brand’s advantage?
We spoke to Managing Consultant Frances Hendry to find out how Blue Latitude Health partnered with a fledgling subsidiary of a pharmaceutical organisation to launch an innovative product in a
complex market.
What does the launch environment look like for this product?
FH: We started working on the product at Phase II and now we’re going into Phase III trials. There is a significant unmet need in this disease area, and everyone is excited about the launch. However, the organisation is still evolving and the team is quite small – naturally this causes a little turbulence.

Aymeric Le Chatelier, Ipsen

A $1B-plus drug stum­bles in­to an­oth­er big PhI­II set­back -- this time flunk­ing fu­til­i­ty test -- as FDA hold re­mains in ef­fect for Ipsen

David Meek

At the time Ipsen stepped up last year with more than a billion dollars in cash to buy Clementia and a late-stage program for a rare bone disease that afflicts children, then CEO David Meek was confident that he had put the French biotech on a short path to a mid-2020 launch.

Instead of prepping a launch, though, the company was hit with a hold on the FDA’s concerns that a therapy designed to prevent overgrowth of bone for cases of fibrodysplasia ossificans progressiva might actually stunt children’s growth. So they ordered a halt to any treatments for kids 14 and under. Meek left soon after to run a startup in Boston. And today the Paris-based biotech is grappling with the independent monitoring committee’s decision that their Phase III had failed a futility test.

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UP­DAT­ED: FDA’s golodirsen CRL: Sarep­ta’s Duchenne drugs are dan­ger­ous to pa­tients, of­fer­ing on­ly a small ben­e­fit. And where's that con­fir­ma­to­ry tri­al?

Back last summer, Sarepta CEO Doug Ingram told Duchenne MD families and investors that the FDA’s shock rejection of their second Duchenne MD drug golodirsen was due to some concerns regulators raised about the risk of infection and the possibility of kidney toxicity. But when pressed to release the letter for all to see, he declined, according to a report from BioPharmaDive, saying that kind of move “might not look like we’re being as respectful as we’d like to be.”

He went on to assure everyone that he hadn’t misrepresented the CRL.

But Ingram’s public remarks didn’t include everything in the letter, which — following the FDA’s surprise about-face and unexplained approval — has now been posted on the FDA’s website and broadly circulated on Twitter early Wednesday.

The CRL raises plenty of fresh questions about why the FDA abruptly decided to reverse itself and hand out an OK for a drug a senior regulator at the FDA believed — 5 months ago, when he wrote the letter — is dangerous to patients. It also puts the spotlight back on Sarepta $SRPT, which failed to launch a confirmatory study of eteplirsen, which was only approved after a heated internal controversy at the FDA. Ellis Unger, director of CDER’s Office of Drug Evaluation I, notes that study could have clarified quite a lot about the benefit and risks associated with their drugs — which can cost as much as a million dollars per patient per year, depending on weight.

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Roche's check­point play­er Tecen­triq flops in an­oth­er blad­der can­cer sub­set

Just weeks after Merck’s star checkpoint inhibitor Keytruda secured FDA approval for a subset of bladder cancer patients, Swiss competitor Roche’s Tecentriq has failed in a pivotal bladder cancer study.

The 809-patient trial — IMvigor010 — tested the PD-L1 drug in patients with muscle-invasive urothelial cancer (MIUC) who had undergone surgery, and were at high risk for recurrence.

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Gilead claims Tru­va­da patents in HHS’ com­plaint are in­valid

Back in November, the Department of Health and Human Services took the rare step of filing a complaint against Gilead for infringing on government-owned patents related to the HIV drug Truvada (emtricitabine/tenofovir disoproxil fumarate) for pre-exposure prophylaxis (PrEP).

But on Thursday, Gilead filed its own retort, making clear that it does not believe it has infringed on the Centers for Disease Control and Prevention’s (CDC) Truvada patents because they are invalid.

Gilead dusts off a failed Ebo­la drug as coro­n­avirus spreads; Ex­elix­is boasts pos­i­tive Ph I/II da­ta

→ Less than a year ago Gilead’s antiviral remdesivir failed to make the cut as investigators considered a raft of potential drugs that could be used against an Ebola outbreak. But it may gain a new mission with the outbreak of the coronavirus in China, which is popping up now around the world.

Gilead put out a statement saying that they’re now in discussions with health officials in the US and China about testing their NUC against the virus. It’s the latest in a growing lineup of biopharma companies that are marshaling R&D forces to see if they can come up with a vaccine or therapy to blunt the spread of the virus, which has now sickened hundreds, killed at least 17 people and led the Chinese government to start quarantining cities.

Alex Karnal (Deerfield)

Deer­field vaults to the top of cell and gene ther­a­py CD­MO game with $1.1B fa­cil­i­ty at Philadel­phi­a's newest bio­phar­ma hub

Back at the beginning of 2015, Deerfield Management co-led a $10 million Series C for a private gene therapy startup, reshaping the company and bringing in new leaders to pave way for an IPO just a year later.

Fast forward four more years and the startup, AveXis, is now a subsidiary of Novartis marketing the second-ever gene therapy to be approved in the US.

For its part, Deerfield has also grown more comfortable and ambitious about the nascent field. And the investment firm is now putting down its biggest bet yet: a $1.1 billion contract development and manufacturing facility to produce everything one needs for cell and gene therapy — faster and better than how it’s currently done.

Tri­fec­ta of sick­le cell dis­ease ther­a­pies ex­tend life ex­pectan­cy, but are not cost-ef­fec­tive — ICER

Different therapeutic traits brandished by the three approved therapies for sickle cell disease all extend life expectancy, but their impact on quality of life is uncertain and their long-term cost-effectiveness is not up to scratch according to the thresholds considered reasonable by ICER, the non-profit concluded in a draft guidance report on Thursday.

Sickle cell disease (SCD), which encompasses a group of inherited red blood cell disorders that typically afflict those of African ancestry, impacts hemoglobin — and is characterized by episodes of searing pain as well as organ damage.