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.

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.

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.