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

Sec­ond PhI­II study for Idor­si­a's sleep drug re­turns pos­i­tive re­sults, but al­so rais­es new ques­tions

Fol­low­ing a suc­cess­ful Phase III study in April show­cas­ing the safe­ty and po­ten­tial of its new sleep drug, Idor­sia post­ed some mixed news in the sec­ond Phase III study, but that won’t stop a planned fil­ing aimed at reg­u­la­to­ry ap­proval.

The drug, a dual orex­in re­cep­tor an­tag­o­nist (DO­RA) called dari­dorex­ant, was found to sig­nif­i­cant­ly im­prove sleep main­te­nance and sub­jec­tive to­tal sleep time in 25 mg dos­es, repli­cat­ing re­sults from the first Phase III study. How­ev­er, im­prove­ments in sleep on­set and day­time func­tion­ing nar­row­ly missed sta­tis­ti­cal sig­nif­i­cance, de­spite nu­mer­i­cal con­sis­ten­cy with the April study.

Idor­sia al­so test­ed 10 mg dos­es of dari­dorex­ant in the study and found pos­i­tive re­sponse across all four ef­fi­ca­cy mea­sures, but all fell short of be­ing sta­tis­ti­cal­ly sig­nif­i­cant.

The new study mea­sured dari­dorex­ant’s ef­fects in 924 adult and el­der­ly pa­tients. Side ef­fects from the tests re­mained low, as with the first study, with se­ri­ous in­stances re­main­ing bal­anced across dosage amounts and place­bos, ac­cord­ing to the biotech.

Re­sults from the two stud­ies re­gard­ing the 25 mg dos­es and place­bos will now be pooled, and some an­a­lysts ex­pect this will of­fer a promis­ing pro­file to take to reg­u­la­tors. Ques­tions will like­ly re­main, how­ev­er, giv­en the cau­tion that reg­u­la­tors usu­al­ly take when ap­prov­ing in­som­nia treat­ments.

Pe­ter Welford at Jef­feries sees the poor re­sults for the low dose as a good thing, as it re­moves any temp­ta­tion the FDA may have to for­go the high dose and go with the less threat­en­ing low­er dose — as they did with Mer­ck. But its suc­cess is still no sure thing.

Im­por­tant­ly the low­er 10mg dose showed small­er non-sig­nif­i­cant ben­e­fits, re­mov­ing the risk reg­u­la­tors en­dorse a sub­op­ti­mal dose to err on the side of cau­tion, in our view. Com­mer­cial un­cer­tain­ties re­main.

In­som­nia drugs gen­er­al­ly are slow to be­come avail­able and are dif­fi­cult to pro­duce. The drugs are al­so heav­i­ly reg­u­lat­ed, as the FDA demon­strat­ed when it im­posed black box warn­ings last year on a slew of more com­mon­ly-known drugs like Lunes­ta, Am­bi­en and Sonata.

Where DO­RAs dif­fer from tra­di­tion­al in­som­nia drugs is in the in­hi­bi­tion of orex­in sig­nal­ing. Orex­ins, dis­cov­ered in 1998, are hor­mones pro­duced by the hy­po­thal­a­mus that reg­u­late sleep, arousal and ap­petite.

On­ly two DO­RAs have hit the mar­ket in the US, but they al­so faced up­hill climbs. Mer­ck’s Bel­som­ra (chem­i­cal­ly known as su­vorex­ant), re­leased in 2014, re­quired warn­ing la­bels re­gard­ing next-day resid­ual ef­fects and abuse po­ten­tial, among oth­er safe­ty risks.

Ad­di­tion­al­ly, Ei­sai’s DO­RA Dayvi­go (lem­borex­ant) scored an FDA ap­proval in De­cem­ber and launched last month but al­so need­ed sim­i­lar warn­ings.

Idor­sia spun off of Swiss phar­ma com­pa­ny Acte­lion af­ter a $30 bil­lion ac­qui­si­tion by John­son & John­son in ear­ly 2017. Idor­sia had been Acte­lion’s old re­search and de­vel­op­ment de­part­ment and is head­ed up by Acte­lion’s founder and CEO, Jean-Paul Clozel. Dari­dorex­ant is one of four de­vel­op­men­tal drugs cur­rent­ly in Idor­sia’s pipeline that has reached the Phase III stage.

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His­toric drug pric­ing re­forms pass; Pfiz­er ac­quires GBT; The long search for non-opi­oid pain drugs; 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.

The Endpoints Weekly has officially crossed the 60,000 mark on subscribers — thanks to all of your support. As the editorial team grows, we’ve been able to do a lot more, with many of those on display this week. Be sure to check out Lei Lei Wu’s deep dive on pain R&D. If you missed it, you may also rewatch her companion panel here.

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Gold for adults, sil­ver for in­fants: Pfiz­er's Pre­vnar 2.0 head­ed to FDA months af­ter Mer­ck­'s green light

Pfizer was first to the finish line for the next-gen pneumococcal vaccine in adults, but Merck beat its rival with a jab for children in June.

Now, two months after Merck’s 15-valent Vaxneuvance won the FDA stamp of approval for kids, Pfizer is out with some late-stage data on its 20-valent shot for infants.

Known as Prevnar 20 for adults, Pfizer’s 20vPnC will head to the FDA by the end of this year for an approval request in infants, the Big Pharma said Friday morning. Discussions with the FDA will occur first and more late-stage pediatric trials are expected to read out soon, informing the regulatory pathway in other countries and regions.

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No­var­tis re­ports two pa­tient deaths af­ter treat­ment with Zol­gens­ma

Two children with spinal muscular atrophy have died after receiving Novartis’ Zolgensma, a gene therapy designed as a one-time treatment for the rare fatal disease.

The deaths, which resulted from acute liver failure, occurred in Russia and Kazakhstan, Novartis confirmed in a statement to Endpoints News. Having notified health authorities across all the markets where Zolgensma is available, it will update the drug label “to specify that fatal acute liver failure has been reported,” a spokesperson wrote.

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House pass­es his­toric drug pric­ing re­forms, lin­ing up decades-in-the-mak­ing win for Biden and De­moc­rats

The US House of Representatives today voted along party lines (all Dems voted for it), 220-207 to pass new, wide-ranging legislation that will allow Medicare drug price negotiations for the first time ever, and cap seniors’ drug expenses to $2,000 per year and seniors’ insulin costs at $35 per month.

Setting up a major victory for President Joe Biden, representatives returned from their summer recess to pass the Inflation Reduction Act, even as many noted the bill would only modestly reduce inflation.

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Senate Finance Committee Chair Ron Wyden (D-OR) (Francis Chung/E&E News/POLITICO via AP Images)

Sen­ate Fi­nance chair con­tin­ues his in­ves­ti­ga­tion in­to phar­ma tax­es with re­quests for Am­gen

Amgen is the latest pharma company to appear on the radar of Senate Finance Committee Chair Ron Wyden (D-OR), who is investigating the way pharma companies are using subsidiaries in low- or zero-tax countries to lower their tax bills.

Like its peers Merck, AbbVie and Bristol Myers Squibb, Wyden notes how Amgen uses its Puerto Rico operations to consistently pay tax rates that are substantially lower than the U.S. corporate tax rate of 21%, with an effective tax rate of 10.7% in 2020 and 12.1% in 2021.

FDA ap­proves sec­ond in­di­ca­tion for As­traZeneca and Dai­ichi's En­her­tu in less than a week

AstraZeneca and Daiichi Sankyo’s antibody-drug conjugate Enhertu scored its second approval in less than a week, this time for a subset of lung cancer patients.

Enhertu received accelerated approval on Thursday to treat adults with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating HER2 (ERBB2) mutations, and who have already received a prior systemic therapy.

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J&J to re­move talc prod­ucts from shelves world­wide, re­plac­ing with corn­starch-based port­fo­lio

After controversially spinning out its talc liabilities and filing for bankruptcy in an attempt to settle 38,000 lawsuits, Johnson & Johnson is now changing up the formula for its baby powder products.

J&J is beginning the transition to an all cornstarch-based baby powder portfolio, the pharma giant announced on Thursday — just months after a federal judge ruled in favor of its “Texas two-step” bankruptcy to settle allegations that its talc products contained asbestos and caused cancer. An appeals court has since agreed to revisit that case.

CSL is gathering its four business units under a unified brand identity strategy (Credit: CSL company site)

CSL brings Se­qirus, Vi­for un­der par­ent um­brel­la brand in iden­ti­ty re­vamp

CSL is gathering its brands under the family name umbrella, renaming its vaccine and newly acquired nephrology specialty businesses with the parent initials.

CSL Seqirus and CSL Vifor join CSL Plasma and CSL Behring as the four now uniformly branded business units of the global biopharma. The Seqirus vaccine division was formed in 2015 with the combination of bioCSL and its purchase of Novartis’ flu vaccine business. CSL picked up Vifor Pharma late last year in an $11.7 billion deal for the nephrology, iron deficiency and cardio-renal drug developer.

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