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.

The Big Phar­ma dis­card pile; Lay­offs all around while some biotechs bid farewell; New Roche CEO as­sem­bles top team; and more

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With earnings seasons in full swing, we’ve listened in on all the calls so you don’t have to. But news is popping up from all corners, so make sure you check out our other updates, too.

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Trodelvy notch­es a win in most com­mon form of breast can­cer

Following a promise last year to go “big and fast in breast cancer,” Gilead has secured a win for Trodelvy in the most common form.

The drug was approved to treat HR-positive, HER2-negative breast cancer patients who’ve already received endocrine-based therapy and at least two other systemic therapies for metastatic cancer, Gilead announced on Friday.

Trodelvy won its first indication in metastatic triple-negative breast cancer back in 2020, and has since added urothelial cancer to the list. HR-positive HER2-negative breast cancer accounts for roughly 70% of new breast cancer cases worldwide per year, according to senior VP of oncology clinical development Bill Grossman, and many patients develop resistance to endocrine-based therapies or worsen on chemotherapy.

Ma­gen­ta halts stem cell work and may sell it­self fol­low­ing pa­tient death, clin­i­cal hold

Magenta Therapeutics said it is halting work on its stem cell transplant drug pipeline and may sell itself, a week after the company reported the death of a patient in an early stage trial of its antibody-drug conjugate.

The Cambridge, MA-based company said it will conduct a “review of strategic alternatives,” and that could include an “acquisition, merger, business combination, or other transaction.”

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Sen. Ron Wyden (D-OR) (Francis Chung/E&E News/Politico via AP Images)

In­fla­tion re­bates in­com­ing: Wyden calls on CMS to move quick­ly as No­var­tis CEO pledges re­ver­sal

Senate Finance Chair Ron Wyden (D-OR) this week sent a letter to the head of the Centers for Medicare & Medicaid Services seeking an update on how and when new inflation-linked rebates will take effect for drugs that see major price spikes.

The newly signed Inflation Reduction Act requires manufacturers to pay a rebate to Medicare when they increase drug prices faster than the rate of inflation.

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Sanofi scraps PhI­II tri­al for Prin­cip­ia drug af­ter re­view­ing com­pe­ti­tion

Months after the FDA placed Phase III trials of Sanofi’s BTK inhibitor on hold, the company is winding down one of the studies.

Sanofi reported in its Q4 earnings that the URSA study “was discontinued after careful evaluation of the emerging competitive treatment landscape in” myasthenia gravis, a rare disease that causes muscle weakness.

The Phase III, placebo-controlled trial was testing tolebrutinib in patients with the moderate-to-severe form of the disease. It started in late 2021, according to records on clinicaltrials.gov, and was originally designed to recruit 154 participants who were receiving the standard of care.

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Raymond Stevens, Structure Therapeutics CEO

Be­hind Fri­day's $161M IPO: A star sci­en­tist, GPCR drug dis­cov­ery and a plan to chal­lenge phar­ma in di­a­betes

What does it take to pull off a $161 million biotech IPO these days?

In Structure Therapeutics’ case, it means having a star scientist co-founder paired with the computational drug discovery company Schrödinger, $198 million in private funding from blue-chip investors, almost six years of research work on G protein-coupled receptors and a slate of oral, small-molecule drugs, with an eye on the huge and growing diabetes and weight-loss market.

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Af­ter 13 years, Ramy Mah­moud steps in­to CEO seat at Opti­nose; Ru­pert Vessey set to ex­it Bris­tol My­ers in Ju­ly

After 13 years as president and COO at Optinose, Ramy Mahmoud has stepped into a new role as its CEO. He is taking the place of Peter Miller, who stepped down earlier this week, though Miller is still staying with the company as a consultant.

In 2010, the two business partners joined Optinose to take it in a new direction, transforming it from a delivery platform to product company. They previously worked together at Johnson & Johnson, when Miller was president at Janssen and Mahmoud headed medical affairs. Miller said after he learned about Optinose, “I did what I always do, which is find people smarter than me to talk with about the idea. And the first person I called was Ramy … and I said, ‘Hey, Ramy, what do you think of this technology?’”

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How to use ex­ter­nal con­trols: FDA spells out think­ing in new draft guid­ance

The use of real-world evidence to inform the FDA’s decision-making continues apace, with the agency releasing new draft guidance yesterday on how sponsors can compare outcomes of trial participants receiving a test treatment with outcomes in a group of people external to the trial.

The practice of externally controlled trials is common, particularly in oncology or other difficult areas where it’s not ethical or feasible to use internal controls.

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The Big Phar­ma axe: Mer­ck cuts chikun­gun­ya vax, Bris­tol My­ers drops Cy­tomX-part­nered pro­gram, and more

As fourth quarter earnings come in, Big Pharmas are disclosing changes to their pipelines during their investor calls, and sometimes more quietly in presentation appendices.

Merck dropped its chikungunya vaccine candidate, which completed a Phase II study. Merck acquired the vaccine through its purchase of Themis Bioscience in 2020. In developing a vaccine for chikungunya, a mosquito-borne virus, Valneva is the frontrunner, as it submitted its vaccine to the FDA at the end of December.

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