Iron­wood, Ab­b­Vie kick de­layed-re­lease Linzess for­mu­la­tion to the curb af­ter tri­al fail­ure

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.

Big Phar­ma's Twit­ter ex­o­dus; Mer­ck wa­gers $1.35B on buy­out; $3.5M gene ther­a­py; 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.

As you start planning for #JPM23, we hope you will consider joining Endpoints News for our live and virtual events. For those who are celebrating Thanksgiving, we hope you are enjoying the long weekend with loved ones. And if you’re not — we’ll see you next week!

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 154,000+ biopharma pros reading Endpoints daily — and it's free.

Paul Perreault, CSL Behring CEO

CSL lands FDA ap­proval for he­mo­phil­ia B gene ther­a­py, sets $3.5M list price

The FDA has approved the world’s first gene therapy for hemophilia B, ushering into the market a treatment that’s historic in both what it promises to do and how much it will cost.

CSL will be marketing the drug, Hemgenix, at a list price of $3.5 million — which sets a new record for the most expensive single-use gene therapy in the US.

In a statement provided to Endpoints News, the Australian company noted that the current costs of treating people with moderate to severe hemophilia B can be significant over a lifetime. By some estimates, healthcare systems could spend more than $20 million per person.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 154,000+ biopharma pros reading Endpoints daily — and it's free.

Image: Shutterstock

MIT re­searchers re­veal DNA "Paste" tech be­hind lat­est gene edit­ing start­up

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.

Elon Musk (GDA via AP Images)

Biggest drug com­pa­nies halt­ed Twit­ter ad buys af­ter Lil­ly in­sulin spoof

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.

J&J's Spra­va­to pulls a PhI­II win against Sero­quel XR in treat­ment-re­sis­tant de­pres­sion

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.

Rob Davis, Merck CEO

Up­dat­ed: No Seagen here: 'Do more' means a small $1.35B pur­chase of Ima­go for Mer­ck

Merck is making an acquisition, the Big Pharma announced before Monday’s opening bell. No, Seagen is not entering the fold, as had been speculated for quarters.

Folding under Merck’s wings will be Pfizer-backed Imago BioSciences. For nearly a year, Merck CEO Rob Davis has been saying the pharma giant needs to “do more” on the business development front after its 2021 $11.5 billion acquisition of Acceleron.

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 154,000+ biopharma pros reading Endpoints daily — and it's free.

Isao Teshirogi, Shionogi president and CEO (Kyodo via AP Images)

Sh­ionogi's Covid an­tivi­ral lands first ap­proval in Japan's new emer­gency ap­proval path­way

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.

Dermavant Sciences' first consumer TV ad for its Vtama psoriasis med shows people ready for a new topical treatment.

Roivant’s Der­ma­vant de­buts first-ever TV com­mer­cial for pso­ri­a­sis cream Vta­ma

Dermavant Sciences has been marketing its first product, psoriasis med Vtama, to dermatologists for months, but on Tuesday it rolled out its first consumer campaign. The debut DTC effort including a streaming TV commercial encourages patients to a “Topical Uprising” in a nod to Vtama being a topical cream.

In the new commercial, a swell of people discards scarves and jacket coverings, gathering in the street to converge on a pharmacy to demand a steroid-free prescription. A moment of levity follows when a pharmacist says, “You know you can just talk to your doctor, right?” The gathered crowds collectively says, “Oh.”

Endpoints News

Keep reading Endpoints with a free subscription

Unlock this story instantly and join 154,000+ biopharma pros reading Endpoints daily — and it's free.

FDA preps for DMD drug gener­ics as Sarep­ta has yet to fin­ish its con­fir­ma­to­ry tri­al

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.