FDA slaps a clin­i­cal hold on mes­sen­ger RNA pro­gram for rare ge­net­ic dis­ease

Trans­late Bio’s plans to put a sec­ond mes­sen­ger RNA drug in the clin­ic in the first half of 2019 has just ground to a halt in front of a sud­den reg­u­la­to­ry red light.

Ron Re­naud

The biotech $TBIO, which went pub­lic in the class of 2018, an­nounced this morn­ing that the FDA has slapped a clin­i­cal hold on its IND for MRT5201. The IV drug is de­signed to ad­dress rare cas­es of or­nithine tran­scar­bamy­lase (OTC) de­fi­cien­cy, an X-linked ge­net­ic dis­ease.

All we know right now is that the FDA has con­veyed ver­bal­ly that reg­u­la­tors have “ad­di­tion­al clin­i­cal and non­clin­i­cal ques­tions” for the biotech. The agency it­self nev­er dis­clos­es its po­si­tion on these cas­es pub­licly. 

Shares in the biotech was down 7.5% mid-day Tues­day — not a dread­ful out­come.

Leerink’s Ge­of­frey Porges talked with the man­age­ment crew, who gave the an­a­lyst the im­pres­sion that this hold was a lot like the tem­po­rary one they got for their lead ef­fort. But what­ev­er in­spired it, the FDA’s de­ci­sion has no im­pact on the top drug for cys­tic fi­bro­sis. He notes:

At this stage it is im­pos­si­ble to tell whether this clin­i­cal hold amounts to a short- or long-term de­vel­op­ment de­lay for MRT5201, but re­gard­less it does not seem to have any spillover im­pli­ca­tions for the com­pa­ny’s prin­ci­pal val­ue dri­ver, which is their lead de­vel­op­ment pro­gram MRT5005 in CF. The com­pa­ny as­sured us that en­roll­ment in the SAD phase of the MRT5005 pro­gram is con­tin­u­ing with­out change, and the com­pa­ny ex­pects to an­nounce the first CF pa­tient en­roll­ment in­to the MAD phase of this tri­al short­ly.

Mes­sen­ger RNA, a field led by a slate of biotechs in­clud­ing Mod­er­na and BioN­Tech, works by de­liv­er­ing code to a cell to in­struct it to make a drug. In this case the cod­ing di­rects liv­er cells to make nor­mal OTC en­zyme. That’s a con­cept that is easy to un­der­stand and dev­il­ish­ly dif­fi­cult to ac­com­plish. 

Trans­late, which is helmed by Ron Re­naud, says it is await­ing for­mal com­mu­ni­ca­tions from the FDA and then will tack­le what­ev­er is­sues are on the ta­ble. The com­pa­ny — which raised $122 mil­lion from its IPO and has a mar­ket cap of $250 mil­lion — has a Phase I/II tri­al un­der­way on cys­tic fi­bro­sis, ac­cord­ing to its web site.

Da­ta Lit­er­a­cy: The Foun­da­tion for Mod­ern Tri­al Ex­e­cu­tion

In 2016, the International Council for Harmonisation (ICH) updated their “Guidelines for Good Clinical Practice.” One key shift was a mandate to implement a risk-based quality management system throughout all stages of a clinical trial, and to take a systematic, prioritized, risk-based approach to clinical trial monitoring—on-site monitoring, remote monitoring, or any combination thereof.

Pfiz­er's big block­buster Xel­janz flunks its post-mar­ket­ing safe­ty study, re­new­ing harsh ques­tions for JAK class

When the FDA approved Pfizer’s JAK inhibitor Xeljanz for rheumatoid arthritis in 2012, they slapped on a black box warning for a laundry list of adverse events and required the New York drugmaker to run a long-term safety study.

That study has since become a consistent headache for Pfizer and their blockbuster molecule. Last year, Pfizer dropped the entire high dose cohort after an independent monitoring board found more patients died in that group than in the low dose arm or a control arm of patients who received one of two TNF inhibitors, Enbrel or Humira.

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Covid-19 roundup: EU and As­traZeneca trade blows over slow­downs; Un­usu­al unions pop up to test an­ti­bod­ies, vac­cines

After coming under fire for manufacturing delays last week, AstraZeneca’s feud with the European Union has spilled into the open.

The bloc accused the pharma giant on Wednesday of pulling out of a meeting to discuss cuts to its vaccine supplies, the AP reported. AstraZeneca denied the reports, saying it still planned on attending the discussion.

Early Wednesday, an EU Commission spokeswoman said that “the representative of AstraZeneca had announced this morning, had informed us this morning that their participation is not confirmed, is not happening.” But an AstraZeneca spokesperson later called the reports “not accurate.”

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Adeno-associated virus-1 illustration; the use of AAVs resurrected the gene therapy field, but companies are now testing the limits of a 20-year-old technology (File photo, Shutterstock)

Af­ter 3 deaths rock the field, gene ther­a­py re­searchers con­tem­plate AAV's fu­ture

Nicole Paulk was scrolling through her phone in bed early one morning in June when an email from a colleague jolted her awake. It was an article: Two patients in an Audentes gene therapy trial had died, grinding the study to a halt.

Paulk, who runs a gene therapy lab at the University of California, San Francisco, had planned to spend the day listening to talks at the American Association for Cancer Research annual meeting, which was taking place that week. Instead, she skipped the conference, canceled every work call on her calendar and began phoning colleagues across academia and industry, trying to figure out what happened and why. All the while, a single name hung in the back of her head.

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Pascal Soriot, AP

As­traZeneca CEO Pas­cal So­ri­ot sev­ers an un­usu­al board con­nec­tion, steer­ing clear of con­flicts while re­tain­ing im­por­tant al­liances

CSL Behring chief Paul Perreault scored an unusual coup last summer when he added AstraZeneca CEO Pascal Soriot to the board, via Zoom. It’s rare, to say the least, to see a Big Pharma CEO take any board post in an industry where interests can simultaneously connect and collide on multiple levels of operations.

The tie set the stage for an important manufacturing connection. The Australian pharma giant agreed to supply the country with 10s of millions of AstraZeneca’s Covid-19 vaccine, once it passes regulatory muster.

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Mer­ck scraps Covid-19 vac­cine pro­grams af­ter they fail to mea­sure up on ef­fi­ca­cy in an­oth­er ma­jor set­back in the glob­al fight

After turning up late to the vaccine development game in the global fight against Covid-19, Merck is now making a quick exit.

The pharma giant is reporting this morning that it’s decided to drop development of 2 vaccines — V590 and V591 — after taking a look at Phase I data that simply don’t measure up to either the natural immune response seen in people exposed to the virus or the vaccines already on or near the market.

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Anthony Fauci, NIAID director (AP Images)

As new Covid-19 task force gets un­der­way, threat looms of vac­cine, mon­o­clon­al an­ti­body-re­sis­tant vari­ants

Hours before President Biden’s Covid-19 team gave their first virtual press conference, the famed AIDS researcher David Ho delivered concerning news in a new pre-print: SARS-CoV-2 B.1.351, the variant that emerged in South Africa, is “markedly more resistant” to antibodies from convalescent plasma and vaccinated individuals.

The news for several monoclonal antibodies, including Eli Lilly’s bamlanivimab, was even worse: Their ability to neutralize was “completely or markedly abolished,” Ho wrote. Lilly’s antibody cocktail, which was just shown to dramatically reduce the risk of hospitalizations or death, also became far less potent.

Florian Brand (L) and Srinivas Rao (ATAI)

Psy­che­del­ic biotech ATAI hopes to ex­pand port­fo­lio through re­search part­ner­ship with Mass Gen­er­al

Psychedelics have made a comeback for mental health research, with companies like startup biotech ATAI Life Sciences raising millions and earning the backing of prominent investors like Peter Thiel, but there’s a hole at the heart of the resurgence: Researchers still don’t fully understand how they work.

A new partnership between ATAI and world-renowned Mass General Hospital hopes to change that.

Bomb squad called to As­traZeneca vac­cine plant; Lu­men nabs CARB-X award for low-cost an­tidiar­rheal

A plant located in Wrexham, Wales that is packing the Oxford/AstraZeneca Covid-19 vaccine into vials was surrounded by a bomb squad after officials called police to report a suspicious package.

The alert caused a partial evacuation of the plant, the BBC was among those to report Wednesday. The owner of the plant, British drugmaker Wockhardt UK, said it was cooperating with local authorities and that there were no reports of any injuries.