The de­layed-re­lease for­mu­la­tion of Iron­wood and Al­ler­gan’s bow­el drug Linzess will not see the light of day.

The ex­per­i­men­tal drug, MD-7246, failed to help pa­tients with ab­dom­i­nal pain as­so­ci­at­ed with ir­ri­ta­ble bow­el syn­drome with di­ar­rhea (IBS-D) in a mid-stage study, prompt­ing the part­ners to aban­don the ther­a­py.

First ap­proved in 2012, Linzess (known chem­i­cal­ly as lina­clotide) en­hances the ac­tiv­i­ty of the in­testi­nal en­zyme guany­late cy­clase-C to in­crease the se­cre­tion of in­testi­nal flu­id and then tran­sit through the in­testi­nal tract, as well as re­duce vis­cer­al pain, to re­lieve pain and con­sti­pa­tion as­so­ci­at­ed with IBS.

MD-7246 was de­signed to sim­ply deal with the pain by tar­get­ing the de­liv­ery of lina­clotide to the colon, where the ma­jor­i­ty of the ab­dom­i­nal pain as­so­ci­at­ed with IBS is be­lieved to orig­i­nate, and to lim­it flu­id se­cre­tion in the small in­tes­tine for a min­i­mal im­pact on bow­el func­tion.

Ear­li­er this week, the part­ners said MD-7246 failed both the main and sec­ondary goals of the 388 pa­tient (IBS-D) Phase II study, but did not dis­close de­tails. Back in 2016, in a tri­al of 532 ir­ri­ta­ble bow­el pa­tients with con­sti­pa­tion (IBS-C), MD-7246 did help im­prove ab­dom­i­nal pain rel­a­tive to place­bo with no ef­fect on bow­el func­tion. In April, Cred­it Su­isse’s Mar­tin Auster had mod­eled ~$300 mil­lion sales op­por­tu­ni­ty for MD-7246 for Iron­wood, based on the com­pa­ny’s sales/re­im­burse­ment ap­por­tion­ment with part­ner Al­ler­gan (now a unit of Ab­b­Vie).

Mark Mal­lon

With MD-7246 in the scrap heap, Iron­wood is left with IW-3718 as the sole clin­i­cal-stage de­vel­op­ment pro­gram, which is cur­rent­ly in late-stage de­vel­op­ment for use in re­frac­to­ry gas­troe­sophageal re­flux dis­ease. An up­date on the pro­gram was ex­pect­ed in the sec­ond half of this year, but will like­ly slide in­to 2021 due to Covid-19-re­lat­ed de­lays.

“As Linzess faces a 2029 hori­zon for gener­ics based on ex­ist­ing set­tle­ments, we an­tic­i­pate the com­pa­ny will take steps to re­place the rev­enue from that fran­chise over the next sev­er­al years by in-li­cens­ing new as­sets. We be­lieve some val­ue-fo­cused share­hold­ers may dis­like this strat­e­gy,” Cowen’s Boris Peak­er wrote in a note on Wednes­day.

Linzess gen­er­at­ed about $803 mil­lion in sales in 2019.

Pe­ter Hecht Cy­cle­ri­on

Last year, Iron­wood shed its oth­er pipeline prospects to fo­cus on GI dis­or­ders, by spin­ning out a com­pa­ny called Cy­cle­ri­on fo­cused on the sol­u­ble guany­late cy­clase (GC) — a key en­zyme in the ni­tric ox­ide sig­nal­ing path­way — busi­ness. The Boston drug­mak­er’s chief Pe­ter Hecht left to head Cy­cle­ri­on, while Iron­wood brought As­traZeneca vet­er­an Mark Mal­lon to the helm.

MIT scientists have developed a tool that they say can insert large gene sequences where they want in the genome.

In a paper published Thursday in Nature Biotechnology, MIT fellows Omar Abudayyeh, Jonathan Gootenberg and colleagues detail a technology they call PASTE, which they say can potentially be used to insert long strands of DNA and treat genetic diseases caused by many different mutations, such as cystic fibrosis and Leber congenital amaurosis, a rare eye disorder that causes blindness.

Almost all of the drug industry’s biggest advertisers cut their spending on Twitter to zero or near-zero over the last two weeks amid worries about impersonation of their brands by pranksters and the future of the social media company.

Among 18 of the biggest pharmaceutical advertisers in the US market, 12 cut their Twitter ad spending to nothing for the week beginning Nov. 14, according to Pathmatics, which tracks data on prescription drug ad spending as well as general corporate advertising. The list of drugmakers cutting spending to zero includes Merck, AstraZeneca, Eli Lilly, Novartis, Pfizer and others.

A day before Thanksgiving, J&J’s Janssen has a new cut of Phase III Spravato data to be grateful for.

The pharma giant announced on Wednesday that its nasal spray, also known as esketamine, beat extended-release quetiapine, previously sold by AstraZeneca as Seroquel XR, in treatment-resistant depression (TRD). Of 676 adults, a significantly higher number of patients on Spravato were able to achieve remission and avoid relapse after 32 weeks, according to J&J.

Japanese regulators on Tuesday signed off on Shionogi’s homegrown antiviral for Covid-19, known as Xocova (ensitrelvir), making it the first approval under Japan’s emergency regulatory approval system.

The emergency approval, following a back-and-forth with regulators since last February, is based on a safety profile with more than 2,000 patients who have accessed the pill, and clinical symptomatic efficacy for five typical Omicron-related symptoms (primary endpoint) and antiviral efficacy (key secondary endpoint) in patients with mild to moderate SARS-CoV-2 infection, regardless of risk factors or vaccination status, and during the Omicron-dominant phase of the pandemic.

The FDA typically releases guidance to help generic drug manufacturers develop new copycats of small molecule drugs, oftentimes in preparation for a brand name product’s patents or exclusivity to expire.

This week, FDA released such bioequivalence guidance for any generic drugmakers looking to take on Sarepta’s Duchenne muscular dystrophy (DMD) drug Exondys 51 (eteplirsen), even though the drug’s sponsor has yet to convert the accelerated approval to a full approval, showing clinical benefit.