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.

Fangliang Zhang, AP Images

UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

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Leen Kawas, Athira CEO (Athira)

Can a small biotech suc­cess­ful­ly tack­le an Ever­est climb like Alzheimer’s? Athi­ra has $85M and some in­flu­en­tial back­ers ready to give it a shot

There haven’t been a lot of big venture rounds for biotech companies looking to run a Phase II study in Alzheimer’s.

The field has been a disaster over the past decade. Amyloid didn’t pan out as a target — going down in a litany of Phase III failures — and is now making its last stand at Biogen. Tau is a comer, but when you look around and all you see is destruction, the idea of backing a startup trying to find complex cocktails to swing the course of this devilishly complicated memory-wasting disease would daunt the pluckiest investors.

GSK presents case to ex­pand use of its lu­pus drug in pa­tients with kid­ney dis­ease, but the field is evolv­ing. How long will the mo­nop­oly last?

In 2011, GlaxoSmithKline’s Benlysta became the first biologic to win approval for lupus patients. Nine years on, the British drugmaker has unveiled detailed positive results from a study testing the drug in lupus patients with associated kidney disease — a post-marketing requirement from the initial FDA approval.

Lupus is a drug developer’s nightmare. In the last six decades, there has been just one FDA approval (Benlysta), with the field resembling a graveyard in recent years with a string of failures including UCB and Biogen’s late-stage flop, as well as defeats in Xencor and Sanofi’s programs. One of the main reasons the success has eluded researchers is because lupus, akin to cancer, is not just one disease — it really is a disease of many diseases, noted Al Roy, executive director of Lupus Clinical Investigators Network, an initiative of New York-based Lupus Research Alliance that claims it is the world’s leading private funder of lupus research, in an interview.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

FDA de­lays de­ci­sion on No­var­tis’ po­ten­tial block­buster MS drug, wip­ing away pri­or­i­ty re­view

So much for a speedy review.

In February, Novartis announced that an application for their much-touted multiple sclerosis drug ofatumumab had been accepted and, with the drug company cashing in on one of their priority review vouchers, the agency was due for a decision by June.

But with June less than 48 hours old, Novartis announced the agency has extended their review, pushing back the timeline for approval or rejection to September. The Swiss pharma filed the application in December, meaning their new schedule will be nearly in line with the standard 10-month window period had they not used the priority voucher.

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Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.