ICER chas­tis­es J&J for over­pric­ing de­pres­sion drug es­ke­t­a­mine ‘where there is such need for treat­ment’

Cog­nizant of the myr­i­ad of ap­proved an­ti­de­pres­sants that of­ten don’t work, reg­u­la­tors en­dorsed J&J’s $JNJ phar­ma­ceu­ti­cal ver­sion of the hal­lu­cino­genic anes­thet­ic ke­t­a­mine — es­ke­t­a­mine — in March for treat­ment-re­sis­tant de­pres­sion, well aware that the orig­i­nal cat tran­quil­iz­er is fre­quent­ly used off-la­bel for se­vere de­pres­sion. On Thurs­day, ICER con­clud­ed that while the drug, sold as Spra­va­to, does con­fer a “promis­ing” clin­i­cal ben­e­fit, its cur­rent list price ex­ceeds a com­mon cost-ef­fec­tive­ness thresh­old by a mod­est mar­gin.

In 2017, an es­ti­mat­ed 17.3 mil­lion adults in the Unit­ed States — rough­ly 7% of all US adults — had at least one ma­jor de­pres­sive episode, ac­cord­ing to the NIH. Most an­ti­de­pres­sants usu­al­ly take a few weeks to work – and half of the pa­tients fail to ful­ly re­spond. The par­ty drug (some­times re­ferred to as Kit Kat or Vi­t­a­min K) and anes­thet­ic ke­t­a­mine which can lift de­pres­sion in many pa­tients with­in hours, must be ad­min­is­tered through in­fu­sion but can have pro­found dis­so­cia­tive side-ef­fects, and pa­tients typ­i­cal­ly re­lapse af­ter treat­ment ends.

Es­ke­t­a­mine is a low-dose, nasal-spray for­mu­la­tion of ke­t­a­mine — but due to its side-ef­fect pro­file, the J&J treat­ment is de­signed to be ad­min­is­tered in the pres­ence of a health­care prac­ti­tion­er.  It was ap­proved on the ba­sis of five piv­otal Phase III stud­ies in pa­tients with treat­ment-re­sis­tant de­pres­sion.

The da­ta used to ap­prove the drug sug­gests it is clin­i­cal­ly ef­fec­tive — but with the ab­sence of long-term safe­ty da­ta, the ev­i­dence is “promis­ing but in­con­clu­sive,” ICER re­searchers said. Since there are no head-to-head tri­als com­par­ing es­ke­t­a­mine with any com­para­tors — such as ke­t­a­mine, elec­tro­con­vul­sive ther­a­py, tran­scra­nial mag­net­ic stim­u­la­tion, oral an­ti­de­pres­sants, or aug­men­ta­tion with an­tipsy­chotics (e.g., olan­za­p­ine) — its rel­a­tive ben­e­fit is al­so hard to judge, they added.

Akin to NICE in the UK, ICER is an in­de­pen­dent body that an­a­lyzes the cost-ef­fec­tive­ness of drugs and oth­er med­ical ser­vices in the Unit­ed States. Un­like NICE, though, ICER is not gov­ern­ment-af­fil­i­at­ed, but its de­ter­mi­na­tions are in­creas­ing­ly be­com­ing in­flu­en­tial with pay­ers.

ICER con­duct­ed its analy­ses us­ing two mea­sures: 1) QALYs, or qual­i­ty-ad­just­ed life-years, a mea­sure of the state of health of a per­son or group in which the ben­e­fits — in terms of length of life — are ad­just­ed to re­flect the qual­i­ty of life. Es­sen­tial­ly, one QALY is equal to one year of life in per­fect health. 2) Life years gained (LYG), which ex­press­es the ad­di­tion­al num­ber of years of life that a per­son lives as a re­sult of re­ceiv­ing treat­ment.

Com­pared with no ad­di­tion­al treat­ment be­yond a back­ground an­ti­de­pres­sant, treat­ment with es­ke­t­a­mine plus a back­ground an­ti­de­pres­sant re­sult­ed in im­por­tant QALY gains in pa­tients with treat­ment-re­sis­tant de­pres­sion (TRD), ICER said.

Us­ing the es­ke­t­a­mine list price of $295 per 28 mg in­tranasal de­vice, the treat­ment’s use re­sults in an in­cre­men­tal cost-ef­fec­tive­ness ra­tio of ap­prox­i­mate­ly $198,000 per QALY com­pared to no ad­di­tion­al treat­ment, ex­ceed­ing the com­mon­ly cit­ed cost-ef­fec­tive­ness thresh­olds of be­tween $50,000-$150,000 per QALY. Mean­while, es­ke­t­a­mine is es­ti­mat­ed to cost ap­prox­i­mate­ly $2.6 mil­lion per life year gained, ICER found.

Es­ke­t­a­mine’s ap­proval was al­so meant to en­hance ac­cess to treat­ment — since ke­t­a­mine is not cov­ered by health in­sur­ers — al­though there is a con­cern that there may still be high out-of-pock­et ex­pens­es through de­ductibles or non-cov­er­age poli­cies.

David Rind

“Es­ke­t­a­mine shows some ben­e­fits for such pa­tients and pro­vides an FDA-ap­proved treat­ment for TRD that may be cov­ered by pay­ers; how­ev­er, it is con­cern­ing to have an over­priced ther­a­py where there is such need for treat­ment. Ad­di­tion­al­ly, the sim­i­lar­i­ty of ke­t­a­mine to es­ke­t­a­mine rais­es is­sues for all stake­hold­ers about how to con­sid­er off-la­bel pre­scrip­tion and cov­er­age of a treat­ment that has not been as well stud­ied but is be­ing in­creas­ing­ly used for TRD,” said ICER’s CMO David Rind in a state­ment.

The ICER re­port was pub­lished on Thurs­day hav­ing in­cor­po­rat­ed the feed­back from pa­tient groups, clin­i­cians, drug man­u­fac­tur­ers, and oth­er stake­hold­ers to the draft ver­sion orig­i­nal­ly un­veiled in March. A fi­nal re­port is ex­pect­ed to be pub­lished in June, fol­low­ing a vote lat­er this month.

J&J dis­agrees with this re­port, a Janssen spokesper­son told End­points News. “It un­der­es­ti­mates the proven short- and long-term ben­e­fits that this treat­ment…brings to TRD pa­tients in need. The in­ac­cu­rate as­sump­tions in the draft re­port re­lat­ed to the pos­i­tive ben­e­fit risk pro­file of Spra­va­to and the com­par­i­son be­tween this FDA ap­proved treat­ment and ke­t­a­mine, a treat­ment be­ing used off-la­bel that has not been ad­e­quate­ly stud­ied and is viewed as ex­per­i­men­tal for TRD, are reck­less.”

Due to a lack of com­par­a­tive da­ta be­tween es­ke­t­a­mine and ke­t­a­mine, ICER was not able to ex­am­ine rel­a­tive cost-ef­fec­tive­ness be­tween the two ther­a­pies. In­stead, the in­sti­tute com­pared the in­di­vid­ual one-year costs and found that es­ke­t­a­mine was ten times more ex­pen­sive than ke­t­a­mine in the first year of use — de­spite the ad­min­is­tra­tion costs as­so­ci­at­ed with pro­vid­ing ke­t­a­mine in­tra­venous­ly.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

What lured Hal Bar­ron away?; Top FDA minds on ac­cel­er­at­ed ap­proval re­forms; ‘Dead wrong’ Aduhelm ad blitz; 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.

Nothing can really compete with Hal Barron’s departure from GlaxoSmithKline as the news of the week, but we do have plenty of original reporting and analysis from the Endpoints team in this edition. Enjoy and have a nice weekend.

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Mer­ck wins le­gal bat­tle over in­sur­ance cov­er­age af­ter ran­somware at­tack

Merck has emerged victorious from a years-long legal battle with insurers over the coverage of more than a billion dollars in losses from the malware NotPetya, with a New Jersey Superior Court judge concluding that the responsibility is on insurers to clarify their policies around cyber attacks.

The pharma giant was one of several victims of a global cyber attack back in 2017 that also hit Danish shipping company Maersk, American food company Mondelēz, French construction giant Saint-Gobain and even the systems monitoring the Chernobyl nuclear power stations, Bloomberg reported back in 2019.

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Crit­ics push back on Alzheimer’s As­so­ci­a­tion ad blitz to get Medicare to change its Aduhelm rul­ing: 'Dead wrong'

The latest Alzheimer’s Association advertising campaign encourages people to fight.

Not against the disease or for more research or treatments, but against the Centers for Medicare and Medicaid Services. More specifically, CMS’ recent reimbursement decision to only pay for Biogen and Eisai’s controversial Alzheimer’s drug Aduhelm for patients in clinical trials.

With CMS’ preliminary decision now in a 30-day comment period, patient advocates’ goal is to convince CMS to reverse its decision with a marketing blitz and public pressure.

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Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Fail­ing to con­firm clin­i­cal ben­e­fit, Gilead pulls 2 ac­cel­er­at­ed ap­proval in­di­ca­tions for can­cer drug

Gilead recently decided to pull two indications for its cancer drug Zydelig — in relapsed follicular B-cell non-Hodgkin lymphoma (FL) and relapsed small lymphocytic leukemia (SLL) — after failing to complete the confirmatory trials required as part of the accelerated approvals from 2014.

“As the treatment landscape for FL and SLL has evolved, enrollment into the confirmatory study has been an ongoing challenge,” Gilead said in a statement, noting it formally notified the FDA of its decision to voluntarily withdraw these indications.

Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

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Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

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

An­oth­er day, an­oth­er xeno­trans­plant, as Unit­ed Ther­a­peu­tics looks to beat com­peti­tors to sci-fi-es­que break­through

Xenotransplantation is having a moment.

Last October, a team from NYU successfully transplanted a kidney from a pig into a brain-dead patient, although observers cast doubt on the importance of the experiment. Then, earlier this month, surgeons at the University of Maryland transplanted a pig heart into a dying human, who appears to still be stable.

Now, another group is planting a flag in the xenotransplantation field. Surgeons at the University of Alabama at Birmingham said Thursday they have achieved the first kidney transplant from a pig to a brain-dead patient, publishing their peer-reviewed findings online. The team, aiming to differentiate itself from the others through the genetic modifications used, is hoping there’s now enough research to soon begin clinical xenotransplantation studies.

Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

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