Taint­ed do­na­tions from stool bank reignite safe­ty con­cerns about poop trans­plants

Last year, the death of an im­muno-com­pro­mised el­der­ly pa­tient in a fe­cal mi­cro­bio­ta trans­plan­ta­tion (FMT) tri­al at the Mass­a­chu­setts Gen­er­al Hos­pi­tal — due to a stool do­na­tion that con­tained a rare type of E. coli bac­te­ria — sent shiv­ers across the field.

Now, an­oth­er in­ci­dent has come to light — this time em­a­nat­ing from the non-prof­it stool bank Open­Bio­me — in which taint­ed stool made six pa­tients sick, four of whom were hos­pi­tal­ized. Two oth­er FMT re­cip­i­ents whose trans­plants com­prised Open­Bio­me’s prod­uct al­so died.

On Thurs­day, the FDA is­sued a safe­ty alert about the po­ten­tial risk of se­ri­ous or life-threat­en­ing in­fec­tions with the use of fe­cal mi­cro­bio­ta for trans­plan­ta­tion — af­ter it had been no­ti­fied that a com­pa­ny’s FMT prod­uct for treat­ment-re­sis­tant C. diff had caused E. coli in­fec­tions in six pa­tients.

Two pa­tients who re­ceived FMT prod­uct that was pre­pared from stool from two dif­fer­ent donors, de­vel­oped EPEC (en­teropath­o­gen­ic E. coli) in­fec­tions. The oth­er four pa­tients — who re­ceived FMT prod­uct that was pre­pared from stool from a sin­gle donor — con­tract­ed STEC (Shi­ga tox­in-pro­duc­ing E. coli) in­fec­tions. Both types of E. coli are path­o­gen­ic, cause di­ar­rhea, and are as­so­ci­at­ed with oth­er symp­toms such as fever, ab­dom­i­nal pain, and vom­it­ing

Open­Bio­me, in a sep­a­rate press re­lease, dis­closed that the taint­ed stool had, in fact, come from three of its donors — and that it was im­me­di­ate­ly im­ple­ment­ing changes to its screen­ing pro­gram to en­sure all FMT ma­te­r­i­al is screened for these pathogens. All un­used ma­te­r­i­al from these three donors has been re­called and de­stroyed, the com­pa­ny added.

Open­Bio­me had been screen­ing for STEC via an en­zyme im­munoas­say, which had come up neg­a­tive, but fol­low­ing the re­ports of the in­fec­tion, the com­pa­ny test­ed the ma­te­r­i­al us­ing PCR test­ing that showed the pres­ence of Shi­ga tox­in pro­duc­tion. Open­Bio­me has not pre­vi­ous­ly screened donors for EPEC, it said, but fol­low-up PCR test­ing of the donor ma­te­r­i­al al­so gen­er­at­ed a pos­i­tive EPEC sig­nal.

Car­olyn Edel­stein

Open­Bio­me is in the process of eval­u­at­ing whether to use PCR test­ing for oth­er pathogens, the non-prof­it com­pa­ny’s ex­ec­u­tive di­rec­tor Car­olyn Edel­stein told End­points News.

“It’s not ob­vi­ous for every pathogen that we screen for that us­ing the PCR method is not go­ing to lead to dif­fer­ent is­sues re­lat­ed to false pos­i­tives as well as false neg­a­tives,” she cau­tioned.

In ad­di­tion, it was al­so dis­closed that two pa­tients with un­der­ly­ing med­ical con­di­tions had died fol­low­ing FMT pro­ce­dures us­ing stool from Open­Bio­me.

It is not clear if STEC in­fec­tions con­tributed to these deaths, the FDA said ini­tial­ly on Thurs­day. Once the agency re­ceived ad­di­tion­al da­ta from Open­Bio­me, it con­clud­ed that the death of one pa­tient — who re­ceived stool that was found not to be con­t­a­m­i­nat­ed with STEC — was un­re­lat­ed to the Open­Bio­me prod­uct. But with the death of the sec­ond pa­tient, whose do­nat­ed stool was not test­ed for STEC, the link was un­clear, the FDA said. Open­Bio­me con­tend­ed that the treat­ing physi­cian had de­ter­mined that death was un­re­lat­ed to STEC.

De­signed to re­plen­ish gut mi­crobes, FMT has shown high rates of ef­fi­ca­cy in the treat­ment of re­cur­rent C. dif­fi­cile, a stub­born in­fec­tion that has grown re­sis­tant to ex­ist­ing an­tibi­otics and kills more than 29,000 Amer­i­cans each year.

Pi­o­neered in Chi­na, the in­ter­ven­tion has gained trac­tion in the Unit­ed States. But the FDA con­sid­ers it an in­ves­ti­ga­tion­al treat­ment with an un­proven safe­ty and ef­fi­ca­cy pro­file — so far. In 2013, the US reg­u­la­tor im­ple­ment­ed a pol­i­cy of “en­force­ment dis­cre­tion” in re­la­tion to FMT for treat­ment-re­frac­to­ry C. diff: While de­vel­op­ers are work­ing on ad­vanc­ing prod­ucts un­der an IND, physi­cians can use FMT prod­ucts af­ter se­cur­ing rea­son­able con­sent from pa­tients.

FMT re­quires a stool sam­ple to be screened, liq­ue­fied and de­liv­ered to the colon by nasal or rec­tal tube. Pa­tients must ei­ther find their own donor, ob­tain vi­able stool from a li­censed health care provider, or turn to a stool bank, such as Open­Bio­me. Few­er than 3% of the pop­u­la­tion qual­i­fy as healthy donors, ac­cord­ing to the Fe­cal Trans­plant Foun­da­tion.

Mike Ro­manos

In 2016, cit­ing safe­ty con­cerns, the FDA ad­vo­cat­ed a re­vi­sion to its pol­i­cy on stool banks — fear­ing that us­ing fe­cal mat­ter from a lim­it­ed num­ber of donors could lead to, for in­stance, the trans­mis­sion of in­fec­tious agents in scores of pa­tients. But the draft guid­ance hasn’t yet been im­ple­ment­ed.

Giv­en the death in the MGH tri­al, and now the Open­Bio­me dis­clo­sure — the time has come for tighter FDA reg­u­la­tion, UK-based Mi­cro­bi­ot­i­ca’s CEO Mike Ro­manos not­ed in an in­ter­view with End­points. “I think what this says is that we need stan­dard­ized screen­ing.”

Im­pli­ca­tions be­yond FMT

Mi­cro­bio­me-based ther­a­peu­tics is a fe­cund field for drug de­vel­op­ers — big and small — cap­i­tal­iz­ing on sci­ence that sug­gests flush­ing ‘good’ gut bac­te­ria in­to the sys­tem can treat a pletho­ra of con­di­tions — from C. diff in­fec­tions to obe­si­ty — us­ing dif­fer­ent ther­a­peu­tic modal­i­ties, some of which are de­signed to side­step the “ick” fac­tor as­so­ci­at­ed with tra­di­tion­al stool trans­fer or FMT. Some com­pa­nies, like Mi­cro­bi­ot­i­ca, are go­ing even fur­ther by work­ing on iso­lat­ing an “ide­al mix” of mi­cro­bic ecosys­tems de­rived from stool — but grow­ing them sep­a­rate­ly once the cock­tail of suit­able bac­te­ria has been se­quenced and char­ac­ter­ized.

A few years ago, the spec­tac­u­lar fail­ure of Seres Ther­a­peu­tics’ sem­i­nal Phase II tri­al test­ing its “crap­sule” — donor-de­rived processed fe­cal ma­te­r­i­al en­cap­su­lat­ed in a pill — de­railed the emerg­ing field. “My hope is that this (Open­Bio­me sit­u­a­tion) doesn’t read across to the whole mi­cro­bio­me field be­cause I think the im­pact of Seres hav­ing an un­suc­cess­ful Phase II…af­fect­ed the whole mi­cro­bio­me field,” Ro­manos said.

When End­points reached out to play­ers in the mi­cro­bio­me ther­a­peu­tics space, the dis­par­i­ties in screen­ing pro­to­cols were ap­par­ent.

Seres, which is ex­pect­ed to un­veil key tri­al da­ta this year, point­ed out in a state­ment that its man­u­fac­tur­ing process dous­es sam­ples in ethanol, which would in­ac­ti­vate po­ten­tial pathogens such as STEC.

French mi­cro­bio­me play­er MaaT Phar­ma, which has a Phase II acute GvHD tri­al on­go­ing, said France’s Na­tion­al Agency of Drugs Safe­ty rec­om­mends FMT do­na­tions be test­ed for STEC, us­ing the PCR method, and that it al­so screens for EPEC among oth­er pathogens us­ing PCR test­ing, in an emailed state­ment to End­points.

A range of key tri­als from com­pa­nies in­clud­ing Re­bi­otix and Finch Ther­a­peu­tics — which was found­ed by mem­bers of the Open­Bio­me team — are ex­pect­ed to read out this year.

Australia’s Avance Clinical: no IND required and a 43.5% rebate on clinical spend for CGT biotechs

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The cell and gene therapies (CGT) sector offers unprecedented opportunities for patient disease management across virtually all therapeutic areas. However, finding the right accredited clinical teams to take a therapy through to the clinic and manage the regulatory process can be a major challenge for biotechs with a CGT product.

Ursula von der Leyen, President of the European Commission

Omi­cron: Re­searchers scram­ble as new coro­n­avirus mu­ta­tion takes flight around the globe — Pfiz­er/BioN­Tech, Mod­er­na vow swift re­sponse

As Americans were waking up for their Black Friday rituals, they were greeted with the news that a new mutation of the Covid-19 virus has appeared and been sequenced — after it caught an international flight to Hong Kong. And two of the leading Covid-19 vaccine developers promised delivery of a new vaccine “within 100 days” if necessary while a third spelled out its 3-prong strategy hours later.

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Thanks­giv­ing edi­tion: Top 15 End­points sto­ries of 2021; Can you name that vac­cine?; Mer­ck­'s Covid an­tivi­ral dis­ap­points; FDA nom­i­nee's in­dus­try ties; 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.

Happy Thanksgiving to all those who are celebrating it — although, if we are being honest, this week’s abbreviated edition is really for those who are not. Wherever you’re tuning in from, we appreciate your support, hope you find this recap helpful and we wish you a wonderful weekend.

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Troy Wilson, Kura CEO

UP­DAT­ED: FDA hits the red light on an ear­ly-stage AML study af­ter a pa­tient dies

The FDA has slapped a clinical hold on the early-stage program for one of Kura Oncology’s cancer drugs following a patient’s death in a clinical trial.

The biotech $KURA reported early Wednesday that the Phase Ib study of KO-539 for acute myeloid leukemia would be halted, suspending enrollment, while researchers and the FDA probed the death. Patients already on the drug can continue taking it.

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What were End­points read­ers tun­ing in­to this year? Here’s a look at our 15 most pop­u­lar re­ports of the year (so far)

At the beginning of this year, I laid out a basic objective for Endpoints News as we headed to our 5th anniversary. We’ve long been doing a fine job covering the breaking news in R&D — if I do say so myself — but we needed to expand our horizons on industry coverage, increase the staff and go much, much deeper when the stories demanded it.

In a phrase: broader and deeper.

It’s safe to say, based on our daily web traffic, that you all seemed to like this idea. We’ve doubled the staff — thanks to a growing group of paid subscribers — ramped up the daily report and now publish a regular slate of in-depth articles. And traffic — those clicks you always read about — have gone up in volume too. Monthly sessions are up 43%, to close to 1.5 million. Unique readers are up 63%, to 874,480 in October, after setting a record of close to a million the month before. Page views are running at 3 million-plus a month. And the overall number of subscribers has surged to 124,000.

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Mar­ket­ingRx roundup: Am­gen, Lil­ly, Bio­haven mi­graine brand re­call low, study says; No­var­tis looks to re­make drug launch mod­el

Forget the migraine marketing brand wars. When it comes to patients, many can’t even name one despite substantial advertising efforts, according to a new study from Phreesia that concludes CGRP migraine drugmakers still need to work on brand recognition.

Almost half (47%) of the patients Phreesia surveyed couldn’t name one preventative migraine brand. The best performer was Topamax, a small molecule anticonvulsant that’s been around since 2004, which 26% of migraine patients could recall. Among the new CGRP brand names recognized, Amgen’s Aimovig ranked highest with 8% recall, while Eli Lilly’s Emgality and Biohaven’s Nurtec tied at 7% and Teva’s Ajovy was remembered by 3% of patients.

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Robert Davis, Merck CEO

Mer­ck shares slide as re­sponse to its oral Covid an­tivi­ral plunges on lat­est up­date

After a second look, Merck says that its big breakthrough on the Covid front doesn’t look so good.

The pharma giant updated its data on its oral antiviral molnupiravir on Friday, and said that its drug reduced the rate of hospitalization and death by 30% — a sharp plunge from the 50% rate reported at the beginning of October during their interim readout.

And the news sparked a sharp retreat on Merck’s shares, which fell 4% ahead of the bell on Friday.

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Emma Walmsley, GlaxoSmithKline CEO (Fang Zhe/Xinhua/Alamy Live News)

Glax­o­SmithK­line places a risky bet on Ar­row­head­'s RNA drug in the fail­ure-strewn NASH field

As activist investors champ at the bit for change at drug giant GlaxoSmithKline, the pharma giant has turned over many rocks to find an R&D success to present to its detractors. In NASH, a field strewn with failures, GSK hopes a new license deal can churn out a much-needed winner.

GSK will pay $120 million in upfront cash and $910 million in downstream milestones to develop and sell ARO-HSD, Arrowhead Pharmaceuticals’ RNA interference drug targeting fatty liver disease nonalcoholic steatohepatitis (NASH), the companies said Monday.

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Name that vac­cine: From Comir­naty to Spike­vax to Nu­vax­ovid, Covid-19 shot­s' brand names re­main lit­tle-known

Most people know if they’re “Team Pfizer” or “Team Moderna,” but few know if they got the Comirnaty or Spikevax Covid-19 vaccine. Those are the brand names of Pfizer and Moderna vaccines, respectively, however they have yet to take hold with consumers, media or even medical professionals.

And there are others. Covid vaccine brand names also include AstraZeneca’s Vaxzevria, Novavax’s Nuvaxovid, and Sanofi and GlaxoSmithKline’s Vidprevtyn. J&J’s Janssen-developed Covid vaccine is the lone major holdout and is still yet to be named, if ever. In EMA filings approving its conditional use, the brand name is listed simply as “Covid-19 Vaccine Janssen.”

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