Ei­sai scores an FDA ap­proval for a home­grown sleep drug

Ei­sai’s bet on a bet­ter in­som­nia drug, whose symp­toms af­fect up to a third of all adults, has been re­ward­ed by the FDA with an ap­proval. But with safe­ty be­ing a big is­sue for sleep drugs, the new ther­a­py faces an up­hill climb to gain ac­cep­tance with doc­tors and pa­tients.

Just ear­li­er this year, the FDA im­posed black box warn­ings on a clutch of in­som­nia drugs, such as Lunes­ta, Sonata, and Am­bi­en, due to re­ports of dan­ger­ous ac­tiv­i­ty such as sleep­walk­ing and sleep-dri­ving that have led to in­juries and deaths.

The new Ei­sai drug Dayvi­go (known chem­i­cal­ly as lem­borex­ant) was de­vel­oped in-house by the Japan­ese drug­mak­er. It works by in­hibit­ing orex­in sig­nal­ing by bind­ing com­pet­i­tive­ly to both orex­in re­cep­tor sub­types (orex­in re­cep­tors 1 and 2). Orex­ins are chem­i­cals in­volved in sleep and arousal nat­u­ral­ly pro­duced by the hy­po­thal­a­mus.

“There’s still un­met need (with­in in­som­nia) as it re­lates to both ef­fi­ca­cy and safe­ty,” Tushar Pa­tel, Ei­sai’s glob­al lead for sleep-wake dis­or­ders in the neu­rol­o­gy busi­ness group, not­ed in an in­ter­view with End­points News. “And we think in Dayvi­go we have a prod­uct that ad­dress­es both (sleep) on­set and main­te­nance, and does that in a way with­out im­pair­ing pos­tur­al sta­bil­i­ty and cog­ni­tion in the morn­ing.”

Dayvi­go was test­ed in two late-stage tri­als, with safe­ty da­ta over a 12 month pe­ri­od. Un­like many old­er in­som­nia drugs, the Ei­sai drug was not as­so­ci­at­ed with re­bound in­som­nia fol­low­ing treat­ment dis­con­tin­u­a­tion. It was al­so test­ed in a trio of safe­ty stud­ies eval­u­at­ing its im­pact on the abil­i­ty to awak­en to sound, next-day pos­tur­al sta­bil­i­ty or mem­o­ry, and next-morn­ing dri­ving im­pair­ment.

Al­though there were no ma­jor dif­fer­ences be­tween Dayvi­go and place­bo on abil­i­ty to awak­en to sound, there was a dose-de­pen­dent wors­en­ing on mea­sures of at­ten­tion and mem­o­ry for the drug ver­sus place­bo. In ad­di­tion, there were no mean­ing­ful dif­fer­ences be­tween the drug and place­bo on next-day pos­tur­al sta­bil­i­ty or mem­o­ry or sta­tis­ti­cal­ly sig­nif­i­cant im­pair­ment in next-morn­ing dri­ving per­for­mance.

In­som­nia suf­fer­ers have a menu of op­tions at their dis­pos­al. They can ac­cess over-the-counter an­ti­his­t­a­mines, ben­zo­di­azepines (such as Dal­mane, Ati­van), non­ben­zo­di­azepine re­cep­tor ag­o­nists (such as Lunes­ta, Am­bi­en), tri­cyclic an­ti­de­pres­sants (such as Silenor), and mela­tonin ag­o­nists (such as Roz­erem).

The most com­mon phar­ma­co­log­i­cal treat­ments are non­ben­zo­di­azepine re­cep­tor ag­o­nists, or Non­BzRAs, which are de­signed to cause sleepi­ness by en­hanc­ing GA­BA — a wide-reach­ing in­hibito­ry neu­ro­trans­mit­ter in the brain. But not all help pa­tients main­tain sleep through the night, and some have a pletho­ra of un­sa­vory side ef­fects in­clud­ing sleep­walk­ing, sleep eat­ing, a height­ened risk of falls and ve­hic­u­lar ac­ci­dents.

The first med­i­cine tar­get­ing orex­in, Mer­ck’s Bel­som­ra, was ap­proved in 2014. Since med­i­cines fo­cused on orex­in — a neu­ro­trans­mit­ter first dis­cov­ered in 1998 — tar­get a more lo­cal­ized area of the brain, the the­o­ry is that they will cause few­er side ef­fects. How­ev­er, Bel­som­ra does car­ry a risk of im­paired dri­ving skills and can en­hance the risk of falling asleep while dri­ving.

There are oth­er drug­mak­ers de­vel­op­ing orex­in med­i­cines for in­som­nia, in­clud­ing Idor­sia and Min­er­va. So what makes Dayvi­go spe­cial?

Ivan Che­ung

“Those oth­er com­pounds are in clin­i­cal de­vel­op­ment — they have shown some­thing, and haven’t shown every­thing,” Ivan Che­ung, chief of neu­rol­o­gy of Ei­sai US, em­pha­sized to End­points, re­fer­ring to sleep on­set, sleep main­te­nance, next morn­ing safe­ty mea­sure­ments, ef­fi­ca­cy over 6 months and safe­ty over 12 months.

“Of course, I’m al­ways about more treat­ment op­tions for more pa­tients,” he said. “All I can say is that it is not an easy task even if you think you have a great mech­a­nis­tic drug to check all those box­es, and I think we’ve checked off a lot of box­es.”

Che­ung did not of­fer any de­tail on the com­pa­ny’s pric­ing plans for the drug in in­som­nia.

Orex­in sig­nal­ing is im­pli­cat­ed in oth­er phys­i­o­log­i­cal func­tions such as mem­o­ry, emo­tions, mo­ti­va­tion, and at­ten­tion. There­fore, Ei­sai is al­so test­ing the drug for use in Alzheimer’s dis­ease, in ad­di­tion to ir­reg­u­lar sleep-wake rhythm dis­or­der. The drug was pre­vi­ous­ly be­ing joint­ly de­vel­oped with Pur­due, but Ei­sai bought back all the rights to it ear­li­er this year.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

So — that pig-to-hu­man trans­plant; Po­ten­tial di­a­betes cure reach­es pa­tient; Ac­cused MIT sci­en­tist lash­es back; 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.

We’re incredibly excited to welcome Beth Bulik, seasoned pharma marketing reporter, to the team. You can find much of her work in our new Marketing channel — and in her weekly newsletter, Endpoints PharmaRx, which will launch in early November. Add it to your subscriptions here.

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

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty

 

I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

Marty Duvall, Oncopeptides CEO

On­copep­tides stock craters as it pulls can­cer drug Pepax­to from the mar­ket

Shares of Oncopeptides crashed more than 70% in early Friday trading after the company said it’s pulling its multiple myeloma drug Pepaxto (melphalan flufenamide) from the US market after failing a confirmatory trial. The move will force the company to close its US and EU business units and enact significant layoffs.

The FDA had scheduled an adcomm meeting next Thursday to discuss Pepaxto, which first won accelerated approval in February and costs about $19,000 per course of treatment. The committee was to weigh in on whether the confirmatory trial demonstrated a worse overall survival in the treatment arm compared to the control arm.

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Pfiz­er pitch­es its Covid-19 vac­cine for younger chil­dren ahead of ad­comm next week

Pfizer will present its case to the FDA’s vaccine adcomm next week, seeking authorization for a lower-dose version of its Covid-19 vaccine for kids ages 5 through 12, which the Biden administration said will likely begin rolling out early next month.

Two primary doses of the 10 µg vaccine (the dose for those ages 12 and up is 30 μg) given 3 weeks apart in this group of children “have shown a favorable safety and tolerability profile, robust immune responses against all variants of concern including Delta, and vaccine efficacy of 90.7% against laboratory-confirmed symptomatic COVID-19,” the company said in briefing documents ahead of next Tuesday’s meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.