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.

Author

Zachary Brennan

managing editor, RAPS

Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,600+ biopharma pros reading Endpoints daily — and it's free.

Novartis CEO Vas Narasimhan [via Bloomberg/Getty]

I’m not per­fect: No­var­tis chief Vas Narasimhan al­most apol­o­gizes in the wake of a new cri­sis

Vas Narasimhan has warily stepped up with what might pass as something close to a borderline apology for the latest scandal to engulf Novartis.

But he couldn’t quite get there.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,600+ biopharma pros reading Endpoints daily — and it's free.

FDA to Sarep­ta: Your wide­ly an­tic­i­pat­ed fol­lowup to Ex­ondys 51 is not get­ting an ac­cel­er­at­ed OK for Duchenne MD

In one of the least anticipated moves of the year, the FDA has rejected Sarepta’s application for an accelerated approval of its Duchenne MD drug golodirsen after fretting over safety issues.

In a statement that arrived after the bell on Monday, Sarepta explained the CRL, saying:

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,600+ biopharma pros reading Endpoints daily — and it's free.

Levi Garraway. Broad Institute via Youtube

Roche raids Eli Lil­ly for its next chief med­ical of­fi­cer as San­dra Horn­ing plans to step down

We found out Monday morning where Levi Garraway was headed after he left Eli Lilly as head of oncology R&D a few days ago. Roche named Garraway as their new chief medical officer, replacing Sandra Horning, who they say is retiring from the company.

Endpoints News

Basic subscription required

Unlock this story instantly and join 57,600+ biopharma pros reading Endpoints daily — and it's free.

Af­ter a posse of Wall Street an­a­lysts pre­dict a like­ly new win for Sarep­ta, we're down to the wire on a crit­i­cal FDA de­ci­sion

As Bloomberg notes, most of the Wall Street analysts that cover Sarepta $SRPT are an upbeat bunch, ready to cheer on the team when it comes to their Duchenne MD drugs, or offer explanations when an odd setback occurs — as happened recently with a safety signal that was ‘erroneously’ reported last week.

Ritu Baral Cowen
Endpoints News

Basic subscription required

Unlock this story instantly and join 57,600+ biopharma pros reading Endpoints daily — and it's free.

UP­DAT­ED: No­var­tis spin­off Nabri­va fi­nal­ly scores its first an­tibi­ot­ic ap­proval

In May, Nabriva Therapeutics suffered a setback after the FDA rejected its antibiotic for complicated urinary tract infections — the Novartis spinoff has now had some better luck with the US agency, which on Monday approved its other drug for community-acquired bacterial pneumonia.

The drug, lefamulin, has been developed as an intravenous and oral formulation and been tested in two late-stage clinical trials. The semi-synthetic compound, whose dosing can be switched between the two formulations, is engineered to inhibit the synthesis of bacterial protein by binding to a part of the bacterial ribosome.

Saqib Islam. CheckRare via YouTube

Spring­Works seeks $115M to push Pfiz­er drugs across fin­ish line while Sat­suma sells mi­graine play in $86M IPO

SpringWorks and Satsuma — both biotech spinouts that have closed B rounds in April — are loading up with IPO cash to boost their respective late-stage plans.
SpringWorks

Bain-backed SpringWorks is the better-known company of the two, and it’s gunning for a larger windfall of $115 million to add to $228 million from previous financings. In the process, the Stamford, CT-based team is also drawing the curtains on the partnerships it has in mind for the pair of assets it had initially licensed from Pfizer.

Mi­nor­i­ty racial groups con­tin­ue to be dis­mal­ly rep­re­sent­ed in can­cer tri­als — study

Data reveal that different racial and ethnic groups — by nature and/or nurture — can respond differently in terms of pharmacokinetics, efficacy, or safety to therapeutics, but this disparity is not necessarily accounted for in clinical trials. A fresh analysis of the last decade of US cancer drug approvals suggests the trend continues, cementing previous research that suggests oncology trials are woefully under-representative of the racial makeup of the real world.

Van­da shares slide af­ter FDA spurns their big end­point and re­jects a pitch on jet lag re­lief

Back in the spring of last year, Vanda Pharmaceuticals $VNDA served up a hot stew of mixed data for a slate of endpoints related to what they called clear evidence that their melatonin sleep drug Hetlioz (tasimelteon) could help millions of travelers suffering from jet lag.

Never mind that they couldn’t get a planned 90 people in the study, settling for 25 instead; Vanda CEO Mihael H. Polymeropoulos said they were building on a body of data to prove it would help jet-lagged patients looking for added sleep benefits. And that, they added, would be worth a major upgrade from the agency as they sought to tackle a big market.