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.

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).

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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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.

Wuhan virus out­break trig­gers in­evitable small-biotech ral­ly

Every few years, a public health crisis (think Ebola, Zika) spurred by a rogue pathogen triggers a small-biotech rally, as drugmakers emerge from the woodwork with ambitious plans to treat the mounting outbreak. In most cases, that enthusiasm never quite delivers.

Things are no different, as the coronavirus outbreak in Wuhan, China takes hold. There have been close to 300 confirmed human infections in China, and at least four deaths. Coronaviruses are a large family of viruses, which include MERS and SARS. On Tuesday, the CDC reported the virus was detected in a US traveler returning from Wuhan.

Brex­it fears, Wood­ford woes over­shad­owed UK biotech and cut 2019 fi­nanc­ing by al­most half

The venture tide might have subsided, the IPO window may be closing and certain listed biotechs may be having a tough time amid Neil Woodford’s well-publicized demised, but there’s still plenty to celebrate in the UK BioIndustry Association’s eyes.

Overall investment in UK biotech last year fell from the record-breaking £2.2 billion levels of 2018 to £1.3 billion — including £679 million in venture capital, a meager £64 million in IPOs plus £596 million when you add up all public financings, according to a new report from the BIA.

Blue­print Med­i­cines po­ten­tial­ly de­lays Ay­vak­it de­ci­sion; Con­trol beats treat­ment in mesothe­lioma tri­al

→ Blueprint Medicines filed an amendment to its application to get the gastrointestinal stromal tumor (GIST) drug Ayvakit approved in fourth-line GIST, the company disclosed in the prospectus for a new $325 million public offering.  Blueprint got a big accelerated OK on the drug this month in a particular mutation, but because the FDA decided to split their review in two, they didn’t hear on fourth-line GIST. They were supposed to hear before February 14, but this amendment could push that date back by 3 months. Blueprint wrote that the amendment is designed to allow the company to comply with the FDA’s request for data from the Phase III Voyage trial before they give a judgment.

Io­n­is, Akcea boost­ed by a pos­i­tive PhII for their No­var­tis castoff car­dio drug — and they plan to push ahead in­to piv­otals

Late last year Novartis abandoned a cardio drug from Ionis’ spinoff Akcea just after the pharma giant snapped up inclisiran, going the RNAi way in guarding against heart disease in the $9.7 billion Medco buyout.

Now the pharma goliath — which is headed down the PCSK9 road with a drug it believes can be used in a mass population — can get a clearer picture of just what they gave up.

Akcea $AKCA and the mother company $IONS put out a statement early Wednesday saying that their Phase II study of AKCEA-APOCIII-LR delivered solid efficacy data, with the high dose clearly outperforming placebo in significantly reducing triglycerides as a means to cutting the risk of cardiovascular disease. In addition, investigators concluded that the drug slashed apoC-III, very low-density lipoprotein and remnant cholesterol while boosting “good” HDL levels.

Hal Barron and Emma Walmsley, GSK

GSK’s ‘break­through’ BC­MA can­cer drug gets a pri­or­i­ty re­view — and a big win for the on­col­o­gy R&D team

After largely whiffing the past 2 years on the pharma R&D front, GlaxoSmithKline research chief Hal Barron has seized boasting rights to a key win that puts them back in the cancer drug development game.

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Who are the young bio­phar­ma lead­ers shap­ing the in­dus­try? Nom­i­nate them for End­points' spe­cial re­port

Update: Nominations open through end of day, Monday, January 27

Two years ago, when we did our first Endpoints 20-under-40, we profiled a set of up-and-comers who promised to help reshape the industry as we know it. Now we’re back and once again looking for the top 20 biopharma professionals under the age of 40. We’ll be profiling folks who have accomplished a lot at a young age but seem on the verge of accomplishing so much more.