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.

BY­OD Best Prac­tices: How Mo­bile De­vice Strat­e­gy Leads to More Pa­tient-Cen­tric Clin­i­cal Tri­als

Some of the most time- and cost-consuming components of clinical research center on gathering, analyzing, and reporting data. To improve efficiency, many clinical trial sponsors have shifted to electronic clinical outcome assessments (eCOA), including electronic patient-reported outcome (ePRO) tools.

In most cases, patients enter data using apps installed on provisioned devices. At a time when 81% of Americans own a smartphone, why not use the device they rely on every day?

Image: Shutterstock

Eli Lil­ly asks FDA to re­voke EUA for Covid-19 treat­ment

Eli Lilly on Friday requested that the FDA revoke the emergency authorization for its Covid-19 drug bamlanivimab, which is no longer as effective as a combo therapy because of a rise in coronavirus variants across the US.

“With the growing prevalence of variants in the U.S. that bamlanivimab alone may not fully neutralize, and with sufficient supply of etesevimab, we believe now is the right time to complete our planned transition and focus on the administration of these two neutralizing antibodies together,” Daniel Skovronsky, Lilly’s CSO, said in a statement.

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As­traZeneca-Alex­ion merg­er slides through FTC re­view af­ter sup­posed M&A crack­down pos­es no bar­ri­ers

The AstraZeneca-Alexion megamerger received a good sign Friday, despite warning signs of the tides turning against large M&A pharma deals.

US regulators at the FTC have cleared the acquisition for approval, AstraZeneca announced, all but signing off on the deal to go through once it officially closes in the third quarter. AstraZeneca originally said it was planning to buy out Alexion back in December for $39 billion.

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J&J faces CDC ad­vi­so­ry com­mit­tee again next week to weigh Covid-19 vac­cine risks

The CDC’s Advisory Committee on Immunization Practices punted earlier this week on deciding whether or not to recommend lifting a pause on the administration of J&J’s Covid-19 vaccine, but the committee will meet again in an emergency session next Friday to discuss the safety issues further.

The timing of the meeting likely means that the J&J vaccine will not return to the US market before the end of next week as the FDA looks to work hand-in-hand with the CDC to ensure the benefits of the vaccine still outweigh the risks for all age groups.

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David Stack, Pacira Biosciences CEO

In high­ly un­usu­al move, Paci­ra sues med­ical jour­nal for li­bel over its non-opi­oid painkiller

A New Jersey biotech whose only approved drug is used as a painkiller after surgeries is suing a scientific journal, its editors and a handful of authors for libel after the publication printed numerous papers and editorials that the company says discredited the drug.

Pacira Biosciences filed the complaint against the American Society of Anesthesiologists in the US District Court for New Jersey on Wednesday afternoon. A February issue of the group’s journal Anesthesiology printed three articles and other content full of “bias” that “seriously disparaged” the drug Exparel, Pacira claimed.

Osman Kibar (Samumed, now Biosplice)

Os­man Kibar lays down his hand at Sa­mumed, step­ping away from CEO role as his once-her­ald­ed an­ti-ag­ing biotech re­brands

Samumed made quite the entrance back in 2016, when it launched with some anti-aging programs and a whopping $12 billion valuation. That level of fanfare was nowhere to be found on Thursday, when the company added another $120 million to its coffers and quietly changed its name to Biosplice Therapeutics.

Why the sudden rebrand?

“We did that for obvious reasons,” CFO and CBO Erich Horsley told Endpoints News. “The name Biosplice echoes our science much more than Samumed does.”

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Ex­clu­sive in­ter­view: Pe­ter Marks on why full Covid-19 vac­cine ap­provals could be just months away

Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, took time out of his busy schedule last Friday to discuss with Endpoints News all things related to his work regulating vaccines and the pandemic.

Marks, who quietly coined the name “Operation Warp Speed” before deciding to stick with his work regulating vaccines at the FDA rather than join the Trump-era program, has been the face of vaccine regulation for the FDA throughout the pandemic, and is usually spotted in Zoom meetings seated in front of his wife’s paintings.

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Near­ly a year af­ter Au­den­tes' gene ther­a­py deaths, the tri­al con­tin­ues. What hap­pened re­mains a mys­tery

Natalie Holles was five months into her tenure as Audentes CEO and working to smooth out a $3 billion merger when the world crashed in.

Holles and her team received word on the morning of May 5 that, hours before, a patient died in a trial for their lead gene therapy. They went into triage mode, alerting the FDA, calling trial investigators to begin to understand what happened, and, the next day, writing a letter to alert the patient community so they would be the first to know. “We wanted to be as forthright and transparent as possible,” Holles told me late last month.

The brief letter noted two other patients also suffered severe reactions after receiving a high dose of the therapy and were undergoing treatment. One died a month and a half later, at which point news of the deaths became public, jolting an emergent gene therapy field and raising questions about the safety of the high doses Audentes and others were now using. The third patient died in August.

“It was deeply saddening,” Holles said. “But I was — we were — resolute and determined to understand what happened and learn from it and get back on track.”

Eleven months have now passed since the first death and the therapy, a potential cure for a rare and fatal muscle-wasting disease called X-linked myotubular myopathy, is back on track, the FDA having cleared the company to resume dosing at a lower level. Audentes itself is no more; last month, Japanese pharma giant Astellas announced it had completed working out the kinks of the $3 billion merger and had restructured and rebranded the subsidiary as Astellas Gene Therapies. Holles, having successfully steered both efforts, departed.

Still, questions about precisely what led to the deaths of the 3 boys still linger. Trial investigators released key details about the case last August and December, pointing to a biological landmine that Audentes could not have seen coming — a moment of profound medical misfortune. In an emerging field that’s promised cures for devastating diseases but also seen its share of safety setbacks, the cases provided a cautionary tale.

Audentes “contributed in a positive way by giving a painful but important example for others to look at and learn from,” Terry Flotte, dean of the UMass School of Medicine and editor of the journal Human Gene Therapy, told me. “I can’t see anything they did wrong.”

Yet some researchers say they’re still waiting on Astellas to release more data. The company has yet to publish a full paper detailing what happened, nor have they indicated that they will. In the meantime, it remains unclear what triggered the events and how to prevent them in the future.

“Since Audentes was the first one and we don’t have additional information, we’re kind of in a holding pattern, flying around, waiting to figure out how to land our vehicles,” said Jude Samulski, professor of pharmacology at UNC’s Gene Therapy Center and CSO of the gene therapy biotech AskBio, now a subsidiary of Bayer.

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Pascal Soriot (AstraZeneca via YouTube)

Af­ter be­ing goad­ed to sell the com­pa­ny, Alex­ion's CEO set some am­bi­tious new goals for in­vestors. Then Pas­cal So­ri­ot came call­ing

Back in the spring of 2020, Alexion $ALXN CEO Ludwig Hantson was under considerable pressure to perform and had been for months. Elliott Advisers had been applying some high public heat on the biotech’s numbers. And in reaching out to some major stockholders, one thread of advice came through loud and clear: Sell the company or do something dramatic to change the narrative.

In the words of the rather dry SEC filing that offers a detailed backgrounder on the buyout deal, Alexion stated: ‘During the summer and fall of 2020, Alexion also continued to engage with its stockholders, and in these interactions, several stockholders encouraged the company to explore strategic alternatives.’

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