FDA snubs Zo­genix's an­ti-seizure drug, not hap­py with some slop­py, in­ad­e­quate R&D work

Nine months af­ter Zo­genix got a stock ral­ly $ZGNX go­ing by tout­ing late-stage da­ta for a new drug to pre­vent seizures due to Dravet syn­drome, the FDA hand­ed back their mar­ket­ing ap­pli­ca­tion with a fail­ing grade on in­ad­e­quate and in­com­plete work. Of­fi­cial­ly, that’s called a refuse-to-file no­tice, which is al­ways em­bar­rass­ing. 

Stephen Farr

It’s not the end of the world, says Zo­genix in a man­ner of speak­ing, but the agency was not hap­py that the biotech had sub­mit­ted an in­cor­rect ver­sion of a dataset with the NDA and fault­ed the com­pa­ny as “cer­tain non-clin­i­cal stud­ies were not sub­mit­ted to al­low as­sess­ment of the chron­ic ad­min­is­tra­tion of fen­flu­ramine.”

In­vestors didn’t like it at all. The biotech, with a mar­ket cap of $2.2 bil­lion, saw its shares tank on the news – plung­ing 32% af­ter the bell.

The EMA, though, hasn’t had any prob­lems with their ap­pli­ca­tion so far, ac­cept­ing it for re­view with an ex­pect­ed de­ci­sion in Q1 2020. And Stifel’s Paul Mat­teis is dis­con­cert­ed by the whole thing.

We find the RTF let­ter for Fin­tepla dis­con­cert­ing, some­what bizarre, and rea­son enough to push back Fin­tepla US rev­enues to 2021 (at a slight­ly re­duced prob­a­bil­i­ty-ad­just­ment), con­ser­v­a­tive­ly as­sum­ing a mean­ing­ful de­lay. That be­ing said, the pre­clin­i­cal tox­i­col­o­gy ask from FDA is le­git­i­mate­ly puz­zling: re­mem­ber, Zo­genix has treat­ed >200 Dravet pa­tients out to 1-year and is cur­rent­ly con­duct­ing a Fin­tepla LGS tri­al that in­cludes an OLE; you’d think that FDA would’ve asked for, or been com­fort­able with, pri­or pre­clin­i­cal tox­i­col­o­gy stud­ies be­fore sign­ing off on the con­duct of ex­ten­sion tri­als.

It was a much dif­fer­ent sto­ry back in the sum­mer of 2018, when com­pa­ny ex­ecs tout­ed pos­i­tive da­ta from their sec­ond Phase III study, not­ing that 43 pa­tients on their drug had a 62.7% drop in seizures, com­pared to 1.2% in the place­bo arm. At that point, the drug was shap­ing up as a di­rect com­peti­tor to GW Phar­ma’s Epid­i­olex, which wowed the in­dus­try with its cannabi­noid ap­proach to re­duc­ing seizures. That drug is billed as a block­buster.

Zo­genix’s drug fen­flu­ramine, you might re­call, was one half of the no­to­ri­ous di­et drug fen-Phen. The biotech says they didn’t see any car­dio is­sues in their small stud­ies, but it does beg the ques­tion on just how high reg­u­la­tors may have raised the bar for an ap­proval — or even ac­cep­tance of an NDA.

“We re­main high­ly con­fi­dent in Fin­tepla’s clin­i­cal pro­file demon­strat­ed in the Phase 3 pro­gram in Dravet syn­drome and are com­mit­ted to ad­vanc­ing the prod­uct can­di­date as a po­ten­tial new treat­ment op­tion for this and oth­er rare and of­ten cat­a­stroph­ic epilep­tic en­cephalopathies,” said CEO Stephen Farr.

In his­toric Covid-19 ad­comm, vac­cine ex­perts de­bate a sea of ques­tions — but of­fer no clear an­swers

The most widely anticipated and perhaps most widely watched meeting in the FDA’s 113-year history ended late Thursday night with a score of questions and very few answers.

For nearly 9 hours, 18 different outside experts listened to public health agencies and foundations present how the United States’ Covid-19 vaccine program developed through October, and they debated where it should go from there: Were companies testing the right metrics in their massive trials? How long should they track patients before declaring a vaccine safe or effective? Should a vaccine, once authorized, be given to the volunteers in the placebo arm of a trial?

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A top drug pro­gram at Bay­er clears a high bar for CKD — open­ing the door to an FDA pitch

Over the past 4 years, Bayer has been steering a major trial through a pivotal program to see if their drug finerenone could slow down the pace of chronic kidney disease in patients suffering from both CKD as well as Type 2 diabetes.

Today, their team jumped on a virtual meeting hosted by the American Society of Nephrology to offer a solid set of pivotal data to demonstrate that the drug can delay dialysis or a kidney replacement as well as cardio disease, while also adding some worrying signs of hyperkalemia among the patients taking the drug. And they’re hustling it straight to regulators in search of an approval for kidney disease and cardio patients — one of the toughest challenges in the book, as demonstrated by repeated past failures.

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Michel Vounatsos, Biogen CEO (via YouTube)

UP­DAT­ED: Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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Biond­Vax stock im­plodes af­ter a big PhI­II gam­ble for its uni­ver­sal flu vac­cine fails

After flying high on Wall Street for the last few months of a pandemic, BiondVax’s stock and dreams of getting approval for its universal flu vaccine hit the windshield.

The Jerusalem-based biotech announced on Friday that its only clinical candidate, M-001, failed both primary and secondary endpoints in a Phase III study. There was no statistically significant difference in reduction of flu illness and severity between the vaccine and placebo groups, according to the company. The vaccine did prove safe, if ineffective, BiondVax said.

Pascal Soriot, AstraZeneca CEO (Zach Gibson/Bloomberg via Getty Images)

UP­DAT­ED: FDA gives As­traZeneca the thumbs-up to restart PhI­II Covid-19 vac­cine tri­als, and J&J is prepar­ing to re­sume its study

Several countries had restarted their portions of AstraZeneca’s global Phase III Covid-19 vaccine trial after the study was paused worldwide in early September, but the US notably stayed on the sidelines — until now. Friday afternoon the pharma giant announced the all clear from US regulators. And on top of that, J&J announced Friday evening that it’s preparing to resume its own Phase III vaccine trial.

Ul­tragenyx in­jects $40M to grab Solid's mi­crody­s­trophin trans­gene — while side­step­ping the AAV9 vec­tor that stirred up safe­ty fears

Since before Ilan Ganot started Solid Bio to develop a gene therapy for kids like his son, who has Duchenne muscular dystrophy, Ultragenyx CEO Emil Kakkis has been watching and advising the former investment banker as he navigated the deep waters of drug development.

Just as Solid is getting back up on its feet after a yearlong clinical hold, Kakkis has decided to jump in for a formal alliance.

With a $40 million upfront, Ultragenyx is grabbing 14.45% of Solid’s shares $SLDB and the rights to its microdystrophin construct for use in combination with AAV8 vectors. Solid’s lead program, which utilizes AAV9, remains unaffected. The company also retains rights to other applications of its transgene.

Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

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Adrian Gottschalk, Foghorn CEO (Foghorn)

Foghorn hits Nas­daq in $120M de­but as the biotech IPO boom shows no sign of slow­ing

It’s been a record year for biotech IPOs, and the execs at Nasdaq would like nothing better than to see that momentum continue into the first half of next year.

Since January, 72 biotech and biopharma companies have hit Wall Street, according to Nasdaq head of healthcare listings Jordan Saxe, together raising $13.2 billion.

The latest is Flagship’s Foghorn Therapeutics, which priced its shares last night at $16 apiece, the midpoint of a $15 to $17 range. The Cambridge, MA-based biotech — which initially filed for a $100 million raise on Oct. 2 — is netting $120 million from a 7.5 million-share offering. The proceeds will go right into its gene traffic control platform, including two lead preclinical oncology candidates.

News brief­ing: Gilead com­pletes $21B buy­out of Im­munomedics; In­nate re­ceives $50M mile­stone pay­ment from As­traZeneca

Gilead’s $21 billion mega-acquisition of Immunomedics is now officially complete, the companies announced Friday morning.

The full merger process took a little over a month, with Gilead and Immunomedics signing an agreement on Sept. 13. Gilead acquired all outstanding stock of Immunomedics for $88 per share, a 108% premium on the previous day’s closing price.

Gilead’s big prize was Trodelvy, approved in July for the treatment of metastatic triple-negative breast cancer. The drug also impressed at last month’s ESMO conference, reducing the risk of death by 52% in a Phase III study.