FDA is­sues an­oth­er safe­ty alert re­lat­ed to fe­cal trans­plants, as da­ta sug­gest coro­n­avirus lingers in poop

Since 2013, the FDA has im­ple­ment­ed a pol­i­cy of “en­force­ment dis­cre­tion” re­gard­ing fe­cal mi­cro­bio­ta trans­plants (FMT) to treat re­frac­to­ry C. diff: While bio­phar­ma com­pa­nies work on de­vel­op­ing stan­dard­ized prod­ucts, physi­cians can con­duct FMT’s af­ter se­cur­ing rea­son­able con­sent from pa­tients. But since last sum­mer, a hand­ful of safe­ty is­sues have caused a stir in the field.

Ear­li­er this week, the FDA is­sued a safe­ty alert high­light­ing the risk of po­ten­tial trans­mis­sion of the new coro­n­avirus from fe­cal mat­ter de­rived from donors used in FMT, and said that ad­di­tion­al safe­ty mea­sures are nec­es­sary.

“Sev­er­al re­cent stud­ies have doc­u­ment­ed the pres­ence of SARS-CoV-2 ri­bonu­cle­ic acid (RNA) and/or SARS-CoV-2 virus (which caus­es Covid-19) in stool of in­fect­ed in­di­vid­u­als. This in­for­ma­tion sug­gests that SARS-CoV-2 may be trans­mit­ted by FMT, al­though the risk of such trans­mis­sion is un­known,” the reg­u­la­tor said in a state­ment.

Ear­li­er this month, an in­ter­na­tion­al pan­el of ex­perts in FMT stressed in an ar­ti­cle in The Lancet Gas­troen­terol­o­gy and He­pa­tol­ogy, that up­dat­ing (at least tem­porar­i­ly) the screen­ing of stool donors is im­per­a­tive — as the risk of trans­mit­ting SARS-CoV-2 by FMT might be high­er than that in oth­er tis­sue trans­plants. A 98-pa­tient study in Chi­na yield­ed da­ta that sug­gest­ed the pos­si­bil­i­ty of ex­tend­ed du­ra­tion of vi­ral shed­ding in fe­ces, for near­ly 5 weeks af­ter the pa­tients’ res­pi­ra­to­ry sam­ples test­ed neg­a­tive for SARS-CoV-2 RNA.

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.

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.

On Mon­day, the FDA is­sued rec­om­men­da­tions to mit­i­gate the risk of se­ri­ous ad­verse events for any fe­cal ma­te­r­i­al that has been do­nat­ed since De­cem­ber 1, 2019 and is be­ing con­sid­ered for use in an FMT pro­ce­dure, in­clud­ing test­ing donors and donor stool for SARS-CoV-2 if fea­si­ble and de­vel­op­ing cri­te­ria to ex­clude of donors and donor stool based on screen­ing and test­ing.

Ear­li­er in March, the FDA is­sued a sep­a­rate safe­ty alert af­ter E. coli-taint­ed stool from the non-prof­it stool bank Open­Bio­me made six pa­tients sick, four of whom were hos­pi­tal­ized. Two oth­er FMT re­cip­i­ents whose trans­plants com­prised Open­Bio­me’s prod­uct al­so died. Last sum­mer, the death of an im­muno-com­pro­mised el­der­ly pa­tient in an 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.

Er­ic Shaff Seres

“These safe­ty alerts point to the fact that donor screen­ing is…nec­es­sary but in­suf­fi­cient to min­i­mize the in­fec­tion risk for donor-de­rived mi­cro­bio­me, and fe­cal trans­plant prod­ucts,” said Er­ic Shaff, CEO of Seres Ther­a­peu­tics, in an in­ter­view.

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.

Now, as Seres awaits the re­sults of a key study, the com­pa­ny was keen to point out in a state­ment that its man­u­fac­tur­ing process in­volves mul­ti­ple lay­ers of test­ing of sam­ples, in­clud­ing the use of ethanol, be­yond the ini­tial screen­ing of fe­cal mat­ter.

What these FDA alerts show is that with FMT, there will al­ways be an is­sue that must be chased, said Seres’ chief tech­nol­o­gy of­fi­cer John Aunins in an in­ter­view.

John Aunins Seres

“You didn’t test pre­vi­ous agents, or you use the test that wasn’t sen­si­tive enough or a pathogen emerges and you don’t have a test for it. So it’s, it’s just an in­her­ent sit­u­a­tion with that kind of a prod­uct.”

Seres’ analy­sis sug­gests that in the case of C. diff, for in­stance, the most ben­e­fit can be de­rived from bac­te­r­i­al spores, and Seres’ man­u­fac­tur­ing ap­pa­ra­tus iso­lates these spores from donor stool.

To be sure, ex­perts ac­knowl­edge that in the gut, it has still not re­al­ly been es­tab­lished what it means to be healthy. The in­ter­ac­tion be­tween the mi­crobes and the host hap­pens in many dif­fer­ent di­men­sions, on an anatom­i­cal lev­el as well as in terms of metabo­lites and im­munol­o­gy — mak­ing the de­ter­mi­na­tion rather com­plex.

For a look at all End­points News coro­n­avirus sto­ries, check out our spe­cial news chan­nel.

Bob Nelsen at the Milken Institute Global Conference on April 29, 2019 in Beverly Hills, California. (Photo by Michael Kovac/Getty Images)

ARCH chief Bob Nelsen has $1.5B to prove 2 sim­ple points: ‘We’re in the most in­no­v­a­tive time ever’ and in­vestors are stay­ing

ARCH co-founder and managing director Bob Nelsen has a well known yen for the home run swing, betting big on potentially transformative meds and tech and the biotech teams he helps bring together. He thrives and bleeds on the cutting edge. And now Nelsen and the ARCH group have debuted 2 big funds to prove that this is the time for the best of biotech to shine — deadly pandemic be damned.

Two new funds, ARCH Venture Fund X and ARCH Venture Fund X Overage, gathered a combined $1.46 billion. And that’s a record. ARCH Venture Fund IX and ARCH Venture Fund IX Overage closed in 2016 with a combined $1.1 billion. ARCH Venture Fund VIII and ARCH Venture Fund VIII Overage closed in 2014 with a combined $560 million.

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UP­DAT­ED: A small, ob­scure biotech just won big with their IPO. In this mar­ket. Are you kid­ding me?

How could a small, largely unknown biotech that emerged from stealth mode just months ago with early-stage cancer programs jump onto Wall Street in the middle of a Category 6 financial hurricane and sail through with a $165 million IPO?

And what does that mean for the rest of the industry waiting to see just how much damage global lockdowns will wreak on clinical development?

The biotech is a company called Zentalis. The crew there nabbed an $85 million crossover round late last year — notably waiting 5 years before waving the numbers around to attract attention, according to my read of a FierceBiotech story. Perceptive joined in, but the syndicate was not in general the kind of marquee affair that gets tongues wagging.

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Aaron Royston, venBio

In­vest­ing in the time of coro­n­avirus: the good, the bad and the hope­ful, as biotech VC firms close funds worth $3B

Apart from disrupting biopharma R&D and regulatory timelines, the coronavirus pandemic has inevitably ravaged financial markets and eroded investor risk appetite. Investing in the time of coronavirus feels reckless, but if biotech venture funds are any indication, the time is ripe.

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Lil­ly Asia Ven­tures co-leads $100M+ round for Chi­nese biotech and its late-stage lu­pus drug

Can a Chinese biotech deliver the first new lupus drug in decades? A high-profile group of VCs are betting on it.

Lilly Asia Ventures and Lake Bleu Capital are the co-headliners for RemeGen’s latest raise, which brought in more than $100 million. Hudson Bay Capital and Vivo Capital — which, like LAV, also invested in a pre-IPO round for Legend Biotech unveiled today — chimed in, as did Janchor Partners and OrbiMed.

GSK's asth­ma bi­o­log­ic Nu­cala is one step clos­er to ap­proval in key chron­ic rhi­nos­i­nusi­tis pop­u­la­tion

Months after GSK’s Nucala cleared in a pivotal rare blood disorder study, the asthma biologic has scored in a late-stage trial in chronic rhinosinusitis patients with nasal polyps.

The British drugmaker on Friday disclosed data from the SYNAPSE study, which tested Nucala (also known as mepolizumab) against a placebo on top of standard-of-care in more than 400 patients, all of whom had a history of previous surgery (approximately one in three had ≥3 surgeries) and required surgery due to severe symptoms and bigger polyps.

Servi­er bags an an­ti­body spe­cial­ist in its lat­est on­col­o­gy M&A deal with plans to add the plat­form tech

Whatever Servier learned about Symphogen during their 2-year development alliance must have significantly whetted their appetite for an acquisition.

Paris-based Servier announced Friday that it has struck a deal to buy out the antibody expert. The acquisition comes 2 years after Servier acquired Shire’s cancer business for $2.4 billion. They’ve been working with Symphogen on a slate of programs, including some favs – PD-1, LAG3 and TIM3 — where they are looking to differentiate themselves from the more prominent drugs in these niches.

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Drug dis­cov­ery in the age of coro­n­avirus

Developing new drugs is incredibly hard. That’s why, despite superhuman efforts from the industry, we’re still looking at 12-18 months minimum before we can realistically hope for a vaccine for Covid-19, and probably months before there’s a proven viable drug treatment.

But our increasing ability to begin to industrialize the drug discovery and development process through an engineering approach means that we have more hope for speeding up this process than ever before — and not just to defeat coronavirus, but to benefit the development of all new medicines in the future.

UP­DAT­ED: Have a new drug that promis­es to fight Covid-19? The FDA promis­es fast ac­tion but some de­vel­op­ers aren't hap­py

After providing an emergency approval to use malaria drugs against coronavirus with little actual evidence of their efficacy or safety in that setting, the FDA has already proven that it has set aside the gold standard when it comes to the pandemic. And now regulators have spelled out a new approach to speeding development that promises immediate responses in no uncertain terms — promising a program offering the ultimate high-speed pathway to Covid-19 drug approvals.

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GSK vac­cine chief heads for AIDS vac­cine ini­tia­tive; Pfiz­er en­lists Sue Desmond-Hell­mann to its board of di­rec­tors

→ Rip Ballou, who until very recently led vaccine research and development at GlaxoSmithKline, is joining the International AIDS Vaccine Initiative (IAVI) to lead its USAID-funded ADVANCE program. The program uses a network of researchers and institutions in Africa to help develop a vaccine for HIV. Ballou had worked at GSK since 2010 and has led global vaccine R&D since 2015. Prior to that he held posts at the Bill & Melinda Gates Foundation, a different post at GSK, Medimmune, and Walter Reed Army Institute of Research.  IAVI is led by Mark Feinberg, the former CSO of Merck Vaccines.