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.

Is a pow­er­house Mer­ck team prepar­ing to leap past Roche — and leave Gilead and Bris­tol My­ers be­hind — in the race to TIG­IT dom­i­na­tion?

Roche caused quite a stir at ASCO with its first look at some positive — but not so impressive — data for their combination of Tecentriq with their anti-TIGIT drug tiragolumab. But some analysts believe that Merck is positioned to make a bid — soon — for the lead in the race to a second-wave combo immuno-oncology approach with its own ambitious early-stage program tied to a dominant Keytruda.

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UP­DAT­ED: Leg­end fetch­es $424 mil­lion, emerges as biggest win­ner yet in pan­dem­ic IPO boom as shares soar

Amid a flurry of splashy pandemic IPOs, a J&J-partnered Chinese biotech has emerged with one of the largest public raises in biotech history.

Legend Biotech, the Nanjing-based CAR-T developer, has raised $424 million on NASDAQ. The biotech had originally filed for a still-hefty $350 million, based on a range of $18-$20, but managed to fetch $23 per share, allowing them to well-eclipse the massive raises from companies like Allogene, Juno, Galapagos, though they’ll still fall a few dollars short of Moderna’s record-setting $600 million raise from 2018.

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As it hap­pened: A bid­ding war for an an­tibi­ot­ic mak­er in a mar­ket that has rav­aged its peers

In a bewildering twist to the long-suffering market for antibiotics — there has actually been a bidding war for an antibiotic company: Tetraphase.

It all started back in March, when the maker of Xerava (an FDA approved therapy for complicated intra-abdominal infections) said it had received an offer from AcelRx for an all-stock deal valued at $14.4 million.

The offer was well-timed. Xerava was approved in 2018, four years after Tetraphase posted its first batch of pivotal trial data, and sales were nowhere near where they needed to be in order for the company to keep its head above water.

Drug man­u­fac­tur­ing gi­ant Lon­za taps Roche/phar­ma ‘rein­ven­tion’ vet as its new CEO

Lonza chairman Albert Baehny took his time headhunting a new CEO for the company, making it absolutely clear he wanted a Big Pharma or biotech CEO with a good long track record in the business for the top spot. In the end, he went with the gold standard, turning to Roche’s ranks to recruit Pierre-Alain Ruffieux for the job.

Ruffieux, a member of the pharma leadership team at Roche, spent close to 5 years at the company. But like a small army of manufacturing execs, he gained much of his experience at the other Big Pharma in Basel, remaining at Novartis for 12 years before expanding his horizons.

Covid-19 roundup: Ab­b­Vie jumps in­to Covid-19 an­ti­body hunt; As­traZeneca shoots for 2B dos­es of Ox­ford vac­cine — with $750M from CEPI, Gavi

Another Big Pharma is entering the Covid-19 antibody hunt.

AbbVie has announced a collaboration with the Netherlands’ Utrecht University and Erasmus Medical Center and the Chinese-Dutch biotech Harbour Biomed to develop a neutralizing antibody that can treat Covid-19. The antibody, called 47D11, was discovered by AbbVie’s three partners, and AbbVie will support early preclinical work, while preparing for later preclinical and clinical development. Researchers described the antibody in Nature Communications last month.

Pfiz­er’s Doug Gior­dano has $500M — and some ad­vice — to of­fer a cer­tain breed of 'break­through' biotech

So let’s say you’re running a cutting-edge, clinical-stage biotech, probably public, but not necessarily so, which could see some big advantages teaming up with some marquee researchers, picking up say $50 million to $75 million dollars in a non-threatening minority equity investment that could take you to the next level.

Doug Giordano might have some thoughts on how that could work out.

The SVP of business development at the pharma giant has helped forge a new fund called the Pfizer Breakthrough Growth Initiative. And he has $500 million of Pfizer’s money to put behind 7 to 10 — or so — biotech stocks that fit that general description.

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Bris­tol My­ers is clean­ing up the post-Cel­gene merg­er pipeline, and they’re sweep­ing out an ex­per­i­men­tal check­point in the process

Back during the lead up to the $74 billion buyout of Celgene, the big biotech’s leadership did a little housecleaning with a major pact it had forged with Jounce. Out went the $2.6 billion deal and a collaboration on ICOS and PD-1.

Celgene, though, also added a $530 million deal — $50 million up front — to get the worldwide rights to JTX-8064, a drug that targets the LILRB2 receptor on macrophages.

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FDA de­lays de­ci­sion on No­var­tis’ po­ten­tial block­buster MS drug, wip­ing away pri­or­i­ty re­view

So much for a speedy review.

In February, Novartis announced that an application for their much-touted multiple sclerosis drug ofatumumab had been accepted and, with the drug company cashing in on one of their priority review vouchers, the agency was due for a decision by June.

But with June less than 48 hours old, Novartis announced the agency has extended their review, pushing back the timeline for approval or rejection to September. The Swiss pharma filed the application in December, meaning their new schedule will be nearly in line with the standard 10-month window period had they not used the priority voucher.

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Mer­ck wins a third FDA nod for an­tibi­ot­ic; Mereo tack­les TIG­IT with $70M raise in hand

Merck — one of the last big pharma bastions in the beleaguered field of antibiotic drug development — on Friday said the FDA had signed off on using its combination drug, Recarbrio, with hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. The drug could come handy for use in hospitalized patients who are afflicted with Covid-19, who carry a higher risk of contracting secondary bacterial infections. Once SARS-CoV-2, the virus behind Covid-19, infects the airways, it engages the immune system, giving other pathogens free rein to pillage and plunder as they please — the issue is particularly pertinent in patients on ventilators, which in any case are breeding grounds for infectious bacteria.