Jean-Paul Clozel, Idorsia CEO (Patrick Straub/Keystone via AP Images)

Piv­otal da­ta sug­gest clean safe­ty pro­file, po­ten­cy could set Idor­si­a's sleep­ing pill apart

Swiss biotech Idor­sia, spun out of Acte­lion af­ter J&J wrapped up its $30 bil­lion takeover in 2017, is one step clos­er to the fin­ish line with a pos­i­tive late-stage study of its in­som­nia drug.

The drug, a dual orex­in re­cep­tor an­tag­o­nist (DO­RA) called dari­dorex­ant, was be­ing test­ed in 930 adult and el­der­ly pa­tients with in­som­nia. Both dos­es (25 and 50 mg) of the ther­a­py im­proved sleep on­set and sleep main­te­nance, as well as sub­jec­tive to­tal sleep time at the end of month 1 and month 3, the com­pa­ny said, with­out dis­clos­ing specifics.

In ad­di­tion, dari­dorex­ant im­proved day­time per­for­mance, as mea­sured by pa­tients feel­ing less phys­i­cal­ly and men­tal­ly tired, less sleepy and more en­er­getic dur­ing the day.

The drug’s side-ef­fect pro­file was al­so large­ly be­nign, with more se­ri­ous ad­verse events on the place­bo arm. There were al­so no next-morn­ing resid­ual ef­fects, re­bound in­som­nia, or with­draw­al symp­toms up­on dis­con­tin­u­a­tion, and no sui­cide, sui­ci­dal ideation or self-in­jury ob­served.

H.C. Wain­wright an­a­lyst Raghu­ram Sel­vara­ju sug­gest­ed its fa­vor­able safe­ty pro­file pits dari­dorex­ant as a “best-in-class drug” with the po­ten­tial for broad pen­e­tra­tion ver­sus ear­li­er-gen­er­a­tion orex­in re­cep­tor mod­u­la­tors, such as Mer­ck’s Bel­som­ra and Ei­sai’s re­cent­ly ap­proved Dayvi­go.

“While we de­signed dari­dorex­ant to have the op­ti­mal pro­file for a sleep med­i­cine, I am none-the-less stunned by the re­sults,” said chief Jean-Paul Clozel in a state­ment. “Once ap­proved, by pro­vid­ing dari­dorex­ant to the mil­lions of pa­tients with in­som­nia, Idor­sia will have a ma­jor im­pact on this med­ical, so­cial, and eco­nom­ic prob­lem. It has struck me par­tic­u­lar­ly in these times of con­fine­ment that we are liv­ing through, that sleep prob­lems are a ma­jor is­sue and re­quire an ex­treme­ly safe and ef­fec­tive drug that can be used by many.”

A sep­a­rate piv­otal tri­al test­ing 10 mg and 25 mg dos­es over three months is ex­pect­ed to read out in the third quar­ter.

The in­som­nia mar­ket is un­der­served, with mul­ti­ple op­tions that car­ry se­ri­ous safe­ty con­cerns such as sleep­walk­ing and sleep-dri­ving —  the best-known ex­am­ples in­clude zolpi­dem (orig­i­nal­ly mar­ket­ed as Am­bi­en), es­zopi­clone (orig­i­nal­ly mar­ket­ed as Lunes­ta) and za­le­plon (for­mer­ly mar­ket­ed as Sonata), as well as ben­zo­di­azepines such as di­azepam, flu­razepam and temazepam, Sel­vara­ju said.

“From our van­tage point, dari­dorex­ant ap­pears much safer than all of these and could po­ten­tial­ly be po­si­tioned as the safest-ever in­som­nia drug, if ap­proved,” he said.

He es­ti­mat­ed peak sales of near­ly $1.3 bil­lion in the Unit­ed States and Eu­rope by 2030.

Back in 2008, Idor­sia par­ent Acte­lion inked a deal worth up to $3.25 bil­lion with GSK for an­oth­er DO­RA, al­morex­ant. At first, al­morex­ant was tagged with sky-high ex­pec­ta­tions in the re­gion of $6 bil­lion in an­nu­al sales, but by 2011, a piv­otal study test­ing the drug was halt­ed due to an undis­closed tol­er­a­bil­i­ty is­sue.

Mer­ck, mean­while, did get a DO­RA on to the mar­ket — Bel­som­ra — al­beit with a la­bel that high­lights the po­ten­tial for abuse and day-af­ter ef­fects, which lim­it­ed its up­take.

Orex­ins, al­so called hypocre­tins, are nat­u­ral­ly pro­duced by the hy­po­thal­a­mus. As some peo­ple with nar­colep­sy ex­pe­ri­ence a loss of orex­in-pro­duc­ing neu­rons, orex­ins are un­der­stood to play a role in wake­ful­ness and arousal.

5AM Ven­tures: Fu­el­ing the Next Gen­er­a­tion of In­no­va­tors

By RBC Capital Markets
With Andy Schwab, Co-Founder and Managing Partner at 5AM Ventures

Key Points

Prescription Digital Therapeutics, cell therapy technologies, and in silico medicines will be a vital part of future treatment modalities.
Unlocking the potential of the microbiome could be the missing link to better disease diagnosis.
Growing links between academia, industry, and venture capital are spinning out more innovative biotech companies.
Biotech is now seen by investors as a growth space as well as a safe haven, fuelling the recent IPO boom.

Biohaven CEO Vlad Coric (Photo Credit: Andrew Venditti)

Pssst: That big Bio­haven Alzheimer's study? It was a bust. Even the sub­group analy­sis ex­ecs tout­ed was a flop

You know it’s bad when a biopharma player plucks out a subgroup analysis for a positive take — even though it was way off the statistical mark for success, like everything else.

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Janet Woodcock and Joshua Sharfstein (AP, Images)

Poll: Should Joshua Sharf­stein or Janet Wood­cock lead the FDA from here?

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As coro­n­avirus vari­ants trig­ger new alarms, the NIH is putting an un­der-the-radar ‘next-gen’ vac­cine in­to PhI

Over the past year, the world has been transfixed by the development of new vaccines to fight SARS-CoV-2. In a frenzy of activity, the new mRNA approach has delivered pioneering emergency approvals in record time. And with some setbacks, the more traditional big players are coming along with added jabs as the most affluent nations in the world begin to vaccinate large portions of their populations.

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The IPO queue adds 5 more biotechs hop­ing to ring in 2021 by blitz­ing Nas­daq

Following a record year for IPOs — in terms of both proceeds and count — there’s already a long lineup of biotechs ready to jump onto Nasdaq in the new year. The companies are likely looking for much higher raises than they initially projected on their S-1s. Now it’s time to see if investors are still hungry for another round of biotech stocks.

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News brief­ing: Beam bags a $260M pri­vate place­ment; mi­Ra­gen re­brands to Virid­i­an Ther­a­peu­tics

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The Beam Therapeutics CEO — and ARCH partner — has pieced together a $260 million private placement from a group of backers that includes Perceptive Advisors, Farallon Capital, Casdin Capital, Redmile Group and Cormorant Asset Management. And there are 3 main goals they’ll pursue with it: clinical development, strategic partnerships and general corporate purposes.

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Janet Woodcock (AP Images)

Janet Wood­cock is in the run­ning for FDA com­mis­sion­er — what does that mean for the agen­cy's fu­ture?

Just a day after reports emerged that Janet Woodcock will serve as interim chief of the FDA, word has gotten out that she is also in the running for the permanent job.

The decision, as the initial wave of reactions suggest, could have dramatic implications for where the agency is headed in the next four years — if not beyond.

Woodcock, the longtime CDER director, is being vetted alongside former FDA principal deputy commissioner Joshua Sharfstein, Bloomberg reported. Already tapped as acting head of the agency, she’s set to take over from Stephen Hahn right after Biden’s inauguration next week.

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