Too slow to warn: Sanofi in­dict­ed over old an­ti-epilep­tic drug tied to birth de­fects

Sanofi has been for­mal­ly charged over De­pakine — a decades-old ther­a­py for epilep­sy that caus­es birth de­fects and im­pedes neu­ro­log­i­cal de­vel­op­ment when tak­en dur­ing preg­nan­cy.

Ev­i­dence that the com­pound — sodi­um val­proate — was as­so­ci­at­ed with neu­rode­vel­op­men­tal risks emerged in the lat­ter half of the 20th cen­tu­ry. In 2014, the EMA re-eval­u­at­ed the drug, and a year lat­er rec­om­men­da­tions that prac­ti­tion­ers should no longer pre­scribe the treat­ment for women of child­bear­ing age or preg­nant women were en­forced.

In 2015, the French so­cial af­fairs in­spec­tion agency (IGAS) chid­ed French health au­thor­i­ties and Sanofi over their re­sponse to the risks re­lat­ed to the drug and its de­riv­a­tives. Soon af­ter, the French pros­e­cu­tor kicked off a pre­lim­i­nary in­ves­ti­ga­tion in­to the ap­proval and sale of De­pakine in Oc­to­ber 2016, Reuters re­port­ed.

The com­pound — which is on the WHO list of “es­sen­tial med­i­cines” — has been on the mar­ket since 1967 to treat epilep­sy and bipo­lar dis­or­der. Sanofi learned of the risk of fe­tus mal­for­ma­tion in the 1980s. In 2003, the com­pa­ny be­came aware of the drug’s im­pact on the neu­ro­log­i­cal de­vel­op­ment of the fe­tus, with a risk of autism or learn­ing dif­fi­cul­ties, ac­cord­ing to the wire agency.

“It’s fi­nal­ly a great vic­to­ry!” tweet­ed Ma­rine Mar­tin, pres­i­dent of the As­so­ci­a­tion for the as­sis­tance of par­ents of chil­dren suf­fer­ing from an­ti-con­vul­sant syn­drome (APE­SAC), which was set up in 2011. “My de­ter­mi­na­tion paid off, we will have our big crim­i­nal tri­al !!!”

The crim­i­nal in­ves­ti­ga­tion was ini­ti­at­ed by APE­SAC, and forms of part of the process of the pend­ing crim­i­nal in­ves­ti­ga­tion on De­pakine be­fore the Ju­di­cial Tri­bunal of Paris, a Sanofi spokesper­son told End­points News.

“This (in­dict­ment) sta­tus will al­low us to as­sert all of our means of de­fence and demon­strate that the com­pa­ny has com­plied with its no­ti­fi­ca­tion oblig­a­tion,” the spokesper­son said.

IGAS has es­ti­mat­ed that be­tween 425 to 450 ba­bies suf­fered con­gen­i­tal birth de­fects or were still­born fol­low­ing ex­po­sure to De­pakine from 2006 to 2014, ac­cord­ing to es­ti­mates cit­ed by Reuters.

Af­ter par­ents of suf­fer­ers crit­i­cized the French state and Sanofi for be­ing too slow to warn about the side ef­fects of the drug — in 2017, a com­pen­sa­tion scheme for vic­tims was set up. Rough­ly 6.5 mil­lion eu­ros has been pro­vid­ed in com­pen­sa­tion to 31 vic­tims, al­though near­ly 2,000 claims have been filed, ac­cord­ing to the French me­dia group fran­ce­in­fo.

Sanofi is not par­tic­i­pat­ing in this fund, the spokesper­son told End­points.

In a 2016 in­ter­view with Reuters, Sanofi said it would ac­cept any blame at­trib­uted by a court over the drug.

On Tues­day, Sanofi in a state­ment that it will “prove it has al­ways com­plied with its du­ty to in­form and been trans­par­ent.”

Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

Vas Narasimhan (AP Images)

UP­DAT­ED: Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

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FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials, and could help shore up public trust in the agency and any eventual vaccine.

Secretary of health and human services Alex Azar speaking in the Rose Garden at the White House (Photo: AFP)

Trump’s HHS claims ab­solute au­thor­i­ty over the FDA, clear­ing path to a vac­cine EUA

The top career staff at the FDA has vowed not to let politics overrule science when looking at vaccine data this fall. But Alex Azar, who happens to be their boss’s boss, apparently won’t even give them a chance to stand in the way.

In a new memorandum issued Tuesday last week, the HHS chief stripped the FDA and other health agencies under his purview of their rule making ability, asserting all such power “is reserved to the Secretary.” Sheila Kaplan of the New York Times first obtained and reported the details of the September 15 bulletin.

Rep. Andy Harris (R-MD) (Tasos Katopodis/Pool via AP Images)

The mi­cro-cap that tapped a mask-skep­tic con­gress­man for their Covid DSMB is ap­ply­ing for an EUA. Their ev­i­dence? 21 pa­tients

NeuroRx, the tiny biotech that came under fire last week after Politico reported they selected a congressman and two other acquaintances of the CEO to supervise their Covid-19 drug trial, announced today that they will ask the FDA to authorize their drug based on the results of just 21 patients.

Such an application would test the agency’s standards of evidence for an EUA, which have already come under scrutiny after controversial authorizations for convalescent plasma and hydroxychloroquine. The only other company to discuss their intention to file for an EUA, Eli Lilly, did so after results came back from a randomized control study testing their antibody in over 450 patients.

PhII Alzheimer's fail­ure deals new blow to Roche, AC Im­mune — but the tau hy­poth­e­sis is far from dead

The leading anti-tau antibody has failed its first Phase II testing, casting a shadow on a popular target (just trailing amyloid beta) for Alzheimer’s disease.

Roche and AC Immune are quick to acknowledge disappointment in the topline readout, which suggested that semorinemab did not reduce cognitive decline among patients with early Alzheimer’s disease, who are either just starting to have symptoms or have mild manifestations.

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Covid-19 roundup: J&J be­gins piv­otal Phase III tri­al for vac­cine; Con­tro­ver­sial hu­man chal­lenge tri­als to be­gin in Lon­don — re­port

Johnson & Johnson announced it’s beginning a pivotal Phase III trial for its Covid-19 candidate, JNJ-78436735 — the first single-dose vaccine in this stage.

The Phase III trial, dubbed ENSEMBLE, will enroll 60,000 patients worldwide, making it the largest Phase III study of a Covid-19 vaccine to date. J&J said the candidate achieved positive interim results in a Phase I/IIa study, which will be published “imminently.” There’s a possibility that the first batches will be ready for potential emergency use in early 2021, according to the biotech.

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Patrick Enright, Longitude co-founder (Longitude)

As its biotechs hit the pan­dem­ic ex­it, Lon­gi­tude rais­es $585M for new neu­ro, can­cer, ag­ing and or­phan-fo­cused fund

The years have been kind to Longitude Capital. This year, too.

A 2006 spinout of Pequot Capital, its founders started their new firm just four years before the parent company would go under amid insider trading allegations. Their first life sciences fund raised $325 million amid the financial crisis, they added a second for $385 million and then in, 2016, a third for $525 million. In the last few months, the pandemic biotech IPO boom netted several high-value exits from those funds, as Checkmate, Vaxcyte, Inozyme and Poseida all went public.

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Scoop: ARCH’s Bob Nelsen is back­ing an mR­NA up­start that promis­es to up­end the en­tire man­u­fac­tur­ing side of the glob­al busi­ness

For the past 2 years, serial entrepreneur Igor Khandros relied on a small network of friends and close insiders to supply the first millions he needed to fund a secretive project to master a new approach to manufacturing mRNA therapies.

Right now, he says, he has a working “GMP-in-a-box” prototype for a new company he’s building — after launching 3 public companies — which plans to spread this contained, precise manufacturing tech around the world with a set of partners. He’s raised $60 million, recruited some prominent experts. And not coincidentally, he’s going semi-public with this just as a small group of pioneers appears to be on the threshold of ushering in the world’s first mRNA vaccines to fight a worldwide pandemic.

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