Ques­tions pile up for No­var­tis as sen­a­tors call on FDA to take ac­tion

Why wait three months to tell the FDA about ma­nip­u­lat­ed da­ta? Why wait two months be­tween doc­u­ment­ing an ini­tial is­sue and open­ing a non­con­for­mance re­port (NCR)? And how harsh­ly will the FDA act?

These ques­tions and more are pil­ing up for No­var­tis, fol­low­ing last week’s an­nounce­ment that the FDA is in­ves­ti­gat­ing the com­pa­ny for ma­nip­u­lat­ing da­ta linked to its $2.1 mil­lion gene ther­a­py Zol­gens­ma (onasemno­gene abepar­vovec-xioi). In Eu­rope, reg­u­la­tors have al­ready pulled the gene ther­a­py’s ac­cel­er­at­ed as­sess­ment for a longer, stan­dard as­sess­ment.

There al­so seem to be dis­crep­an­cies be­tween what No­var­tis CEO Vas­ant Narasimhan has said and what the FDA has found. For in­stance, Narasimhan said in an in­vestor call that the com­pa­ny launched an in­ter­nal in­ves­ti­ga­tion in­to the da­ta ma­nip­u­la­tions as soon as it learned of them in mid-March be­fore launch­ing a “full tech­ni­cal qual­i­ty in­ves­ti­ga­tion” in May.

Wil­son Bryan

But the re­cent­ly re­leased FDA Form 483 said there is “no doc­u­men­ta­tion” as to why an NCR was not opened un­til 15 May when the ini­tial al­le­ga­tion is doc­u­ment­ed as hav­ing been re­port­ed on 14 March. FDA al­so said, “There is no doc­u­men­ta­tion in this NCR that an au­dit of all oth­er po­ten­tial­ly im­pact­ed da­ta, stud­ies, and re­ports was con­duct­ed or is planned to de­ter­mine if there was ev­i­dence of da­ta mis­man­age­ment or ma­nip­u­la­tion or a jus­ti­fi­ca­tion for not con­duct­ing or plan­ning such an au­dit.”

A Ju­ly mem­o­ran­dum from Wil­son Bryan, di­rec­tor of the FDA’s Of­fice of Tis­sues and Ad­vanced Ther­a­pies, al­so notes that this will not be re­solved in a quick man­ner and how the re­sults from the Phase III tri­al do not ap­pear to be im­pact­ed.

“A com­plete as­sess­ment of the im­pact of the da­ta ma­nip­u­la­tion will re­quire ad­di­tion­al in­ves­ti­ga­tion, dis­cus­sions both in­ter­nal­ly with­in CBER and with AveX­is, will prob­a­bly re­quire that AveX­is sub­mit and FDA re­view one or more BLA sup­ple­ments, and may take at least sev­er­al months,” Bryan wrote. “The da­ta ma­nip­u­la­tion seems like­ly to im­pact the in­ter­pre­ta­tion of the Phase 1 clin­i­cal tri­al re­sults, as well as the in­ter­pre­ta­tion of the re­sults of some, but not all, of the non­clin­i­cal stud­ies in the orig­i­nal BLA. At this time, the da­ta ma­nip­u­la­tion does not ap­pear to im­pact the in­ter­pre­ta­tion of the re­sults of the an­i­mal tox­i­col­o­gy stud­ies or the Phase 3 clin­i­cal tri­al.”

Five De­mo­c­ra­t­ic sen­a­tors (in­clud­ing pres­i­den­tial hope­fuls Bernie Sanders and Eliz­a­beth War­ren) pounced on the da­ta ma­nip­u­la­tion, say­ing this “scan­dal smacks of the phar­ma­ceu­ti­cal in­dus­try’s priv­i­lege and greed.” They al­so called on the FDA to hold No­var­tis’s AveX­is ac­count­able and they ques­tioned whether the FDA has plans to re-is­sue a fi­nal rule on fal­si­fied da­ta that the agency was plan­ning to with­draw this month.

AveX­is spokes­woman told Fo­cus: “We have and will con­tin­ue to work in close co­op­er­a­tion with the FDA to ap­pro­pri­ate­ly up­date our BLA sub­mis­sion and ad­dress any qual­i­ty gaps iden­ti­fied.”

And Zol­gens­ma aside, this is not the first time FDA has raised con­cerns about No­var­tis’s clin­i­cal tri­al op­er­a­tions in re­cent months.

RAPS: First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.


Zachary Brennan

managing editor, RAPS

Amarin CEO John Thero discussing the company's plans for Vascepa, August 2019 — via Bloomberg

Amarin wins a block­buster ap­proval from the FDA. Now every­one can shift fo­cus to the patent

For all those people who could never quite believe that Amarin $AMRN would get an expanded label with blockbuster implications, the stress and anxiety on display right up to the last minute on Twitter can now end. But new, pressing questions will immediately surface now that the OK has come through.

On Friday afternoon, the FDA stamped its landmark approval on the industrial strength fish oil for reducing cardio risks for a large and well defined population of patients. The approval doesn’t give Amarin everything it wants in expanding its use, losing out on the primary prevention group, but it goes a long way to doing what the company needed to make a major splash. The approval was cited for patients with “elevated triglyceride levels (a type of fat in the blood) of 150 milligrams per deciliter or higher. Patients must also have either established cardiovascular disease or diabetes and two or more additional risk factors for cardiovascular disease.”

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Sarep­ta was stunned by the re­jec­tion of Vyondys 53. Now it's stun­ning every­one with a sur­prise ac­cel­er­at­ed ap­proval

Sarepta has a friend in the FDA after all. Four months after the agency determined that it would be wrong to give Sarepta an accelerated approval for their Duchenne MD drug golodirsen, regulators have executed a stunning about face and offered the biotech a quick green light in any case.

It was the agency that first put out the news late Thursday, announcing that Duchenne MD patients with a mutation amenable to exon 53 skipping will now have their first targeted treatment: Vyondys 53, or golodirsen. Having secured the OK via a dispute resolution mechanism, the biotech said the new drug has been priced on par with their only other marketed drug, Exondys 51 — which for an average patient costs about $300,000 per year, but since pricing is based on weight, that sticker price can even cross $1 million.

Sarepta shares $SRPT surged 23% after-market to $124.

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Paul Hudson, Getty Images

UP­DAT­ED: Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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Paul Biondi (File photo)

Paul Biondi's track record at Bris­tol-My­ers cov­ered bil­lions in deals of every shape and size. Here's the com­plete break­down

Paul Biondi was never afraid to bet big during his stint as business development chief at Bristol-Myers Squibb. And while the gambles didn’t all pay out, by any means, his roster of pacts illustrates the broad ambitions the pharma giant has had over the last 5 years — capped by the $74 billion Celgene buyout.

On Thursday, we learned that Biondi had exited the company. And Chris Dokomajilar at DealForma came up with the complete breakdown on every buyout, licensing pact and product purchase Bristol-Myers forged during his tenure in charge of the BD team at one of the busiest companies in biopharma.

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Arie Belldegrun (Photo: Jeff Rumans for Endpoints News)

Ju­ry finds Gilead li­able for $585M and big roy­al­ties in Kite CAR-T patent case

A Kite deal that’s already become a burden on Gilead’s back just got heavier as a California jury has ruled Gilead must pay Bristol-Myers Squibb and Sloan Kettering $585 million plus a 27.6% royalty for patent infringement committed by its subsidiary. The ruling is almost certain to be appealed.

Kite Pharma — founded by Arie Belldegrun, now focused on a next-gen CAR-T company — has been facing a lawsuit since the day its first CAR–T therapy won approval in October, 2017. Juno Therapeutics and Sloan Kettering filed a complaint saying Kite had copied its technology. Gilead acquired Kite in June of that year for $11.9 billion.  Juno was acquired the following year by Celgene for $9 billion, before Celgene was acquired by Bristol-Myers Squibb in 2019.

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FDA ex­pert pan­el unan­i­mous­ly rec­om­mends ap­proval for Hori­zon Ther­a­peu­tics eye drug

An FDA advisory committee noted with concern a small safety database but unanimously endorsed a Horizon Therapeutics drug for a rare eye autoimmune disease that can blind patients: teprotumumab for thyroid eye disease (TED).

“It was a pretty easy vote,” said Erica Brittain, an NIH biostatistician and one of the 12 panelists on FDA’s Dermatologic and Ophthalmic Drugs Advisory Committee.

This image shows a lab technician measuring the zone of inhibition during an antibiotic sensitivity test, 1972. The zone of inhibition is measured and compared to a standard in order to determine if an antibiotic is effective in treating the bacterial infection. (Gilda Jones/CDC via Getty Images)

Bio­phar­ma has aban­doned an­tibi­ot­ic de­vel­op­ment. Here’s why we did, too.

Timing is Everything
When we launched Octagon Therapeutics in late 2017, I was convinced that the time was right for a new antibiotic discovery venture. The company was founded on impressive academic pedigree and the management team had known each other for years. Our first program was based on a compelling approach to targeting central metabolism in the most dangerous bacterial pathogens. We had already shown a high level of efficacy in animal infection models and knew our drug was safe in humans.

Paul Biondi (File photo)

Bris­tol-My­er­s' strat­e­gy, BD chief Paul Bion­di ex­it­ed the com­pa­ny — just ahead of the $74B Cel­gene deal close

Paul Biondi, who orchestrated billions of dollars in deals for Bristol-Myers Squibb over the 5 years he’s run their business development team, has exited the company. Biondi left last month, according to a company spokesperson, in pursuit of another — unspecified — external opportunity.

After 17 years with Bristol-Myers Squibb, Paul Biondi, Head of Strategy and Business Development, decided to leave the company to pursue an external opportunity. The company wishes him well in his new endeavors. Bristol-Myers Squibb  is actively searching for Paul’s successor, and will make an announcement, as appropriate.

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Arie Belldegrun at UKBIO 2019. Shai Dolev for Endpoints News

Kite Phar­ma's ex-CEO con­tra­dicts founder as CAR-T patent tri­al heats up, with con­flict­ing val­u­a­tions

Two days after Kite Pharma founder Arie Belldegrun told a federal courtroom that a meeting he had with a Memorial Sloan Kettering executive wasn’t about licensing their immunotherapy patent, Kite’s ex-CEO Aya Jakobovits said it was.

The admission came Tuesday during cross-examination in a patent infringement case that features two of the biggest cancer biotechs and some of the most well-known names in American medicine.

Jakobovits initially said she was not in attendance, didn’t know it was going to happen and didn’t know what took place, according to Law360. But then the plaintiff’s lawyer handed her a document – whose contents were not publicly revealed – and asked again if she learned after-the-fact that the meeting involved a potential patent license.

“Yes,” Jakobovits eventually said.

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