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.

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