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.

No­var­tis reshuf­fles its wild cards; Tough sell for Bio­gen? Googling pro­teins; Ken Fra­zier's new gig; 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.

If you enjoy the People section in this report, you may also want to check out Peer Review, my colleagues Alex Hoffman and Kathy Wong’s comprehensive compilation of comings and goings in biopharma.

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Demis Hassabis, DeepMind CEO (Qianlong/Imaginechina via AP Images)

Google's Deep­Mind opens its pro­tein data­base to sci­ence — po­ten­tial­ly crack­ing drug R&D wide open

Nearly a year ago, Google’s AI outfit DeepMind announced they had cracked one of the oldest problems in biology: predicting a protein’s structure from its sequence alone. Now they’ve turned that software on nearly every human protein and hundreds of thousands of additional proteins from organisms important to medical research, such as fruit flies, mice and malaria parasite.

The new database of roughly 350,000 protein sequences and structures represents a potentially monumental achievement for the life sciences, one that could hasten new biological insights and the development of new drugs. DeepMind said it will be free and accessible to all researchers and companies.

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In­side Bio­gen's scram­ble to sell Aduhelm: Pro­ject 'Javelin' and pres­sure to ID as many pa­tients as pos­si­ble

In anticipation of Aduhelm’s approval for Alzheimer’s in June, Biogen employees were directed to identify and guarantee treatment centers would administer the drug through a program called “Javelin,” a senior Biogen employee told Endpoints News.

The program identified about 800 centers for use, he said, and Biogen now pays for the use of bioassays to identify beta amyloid in potential patients having undergone a lumbar puncture procedure, the employee said — and one center preparing to administer the drug confirmed its participation in the bioassay program.

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EMA re­jects FDA-ap­proved Parkin­son's drug, signs off on Mod­er­na vac­cine use in ado­les­cents ahead of FDA

The European Medicines Agency on Friday rejected Kyowa Kirin’s Parkinson’s disease drug Nouryant (istradefylline), which the US FDA approved in 2019 under the brand name Nourianz.

EMA said it considered that the results of the clinical studies used to support the application “were inconsistent and did not satisfactorily show that Nouryant was effective at reducing the ‘off’ time. Only four out of the eight studies showed a reduction in ‘off’ time, and the effect did not increase with an increased dose of Nouryant.”

6 top drug­mak­ers of­fer per­spec­tives on FDA's new co­vari­ates in RCTs guid­ance

Back in May, the FDA revised and expanded a 2019 draft guidance that spells out how to adjust for covariates in the statistical analysis of randomized controlled trials.

Building on the ICH’s E9 guideline on the statistical principles for clinical trials, the 3-page draft was transformed into an 8-page draft, with more detailed recommendations on linear and nonlinear models to analyze the efficacy endpoints in RCTs.

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Vas Narasimhan, Novartis CEO (Jason Alden/Bloomberg via Getty Images)

No­var­tis dis­cards one of its ‘wild card’ drugs af­ter it flops in key study. But it takes one more for the hand

Always remember just how risky it is to gamble big on small studies.

A little more than 4 years ago, Novartis reportedly put up a package worth up to $1 billion for the dry eye drug ECF843 after a small biotech called Lubris put it through its paces in a tiny study of 40 moderate to severe patients, tracking some statistically significant markers of efficacy.

By last fall, the program had risen up to become one of CEO Vas Narasimhan’s top “wild card” programs in line for a potential breakthrough year in 2021. These drugs were all considered high-risk, high-reward efforts. And in this case, risk won.

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No­var­tis to pay near­ly $178M in law­suit over BRAF drug — and will be on the hook for roy­al­ty

After a four-year battle over a cancer drug patent, Novartis has been ordered by a California judge to pay a Daiichi Sankyo subsidiary $177.8 million.

Plexxikon filed a lawsuit against the pharma giant in 2017, alledging that Tafinlar, a rival to its melanoma drug Zelboraf that was brought to market in collaboration with Roche, has stepped on its intellectual property. The jury ruled in its favor, adding that the infringement is in fact willful.

Al Sandrock, Biogen R&D chief (Biogen via YouTube)

Bio­gen has a shaky end to H1 with a $542M write-off adding to its woes — but an­a­lysts see big rev­enue ahead for Aduhelm

All eyes at Biogen’s Q2 earnings call Thursday were on Aduhelm, but investors also got a glimpse of what Biogen would have faced had the FDA not opted to approve their controversial Alzheimer’s drug.

That glimpse, revealing a combination of declining sales, growing competition and failed medicines, underscores the stakes of the big biotech’s Aduhelm efforts, as execs punch back at the criticism they’ve engendered in the political and medical world and vigorously pushes its sales staff to roll out the drug as fast as possible.

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Michel Vounatsos, Biogen CEO (Credit: World Economic Forum/Valeriano Di Domenico)

Bio­gen de­fends slow roll­out of new Alzheimer's drug, crit­i­cizes neg­a­tive me­dia at­ten­tion

As Biogen execs bemoaned the negative media coverage around Aduhelm’s approval a month ago, the biotech isn’t gaining much traction yet in using its new drug, largely due to a lack of insurance coverage, according to an earnings call Thursday.

Management indicated that of the nearly 900 sites that were prepped and ready following Aduhelm’s approval, 325 of those, or about 35%, have completed a positive pharmacy and therapeutics (P&T) review or won’t require one. The review is a step some hospitals or health systems take prior to using a new drug. Some major sites, however, have said they won’t participate.