No­var­tis ad­mits to ‘mis­take’ af­ter par­tial clin­i­cal hold placed on Zol­gens­ma tri­al

No­var­tis on Wednes­day said that the FDA placed a par­tial hold on in­trathe­cal clin­i­cal tri­als of its gene ther­a­py Zol­gens­ma (onasemno­gene abepar­vovec-xioi) for spinal mus­cu­lar at­ro­phy (SMA) pa­tients based on find­ings in a small pre­clin­i­cal an­i­mal study.

On Thurs­day, a No­var­tis spokesper­son told Fo­cus that a draft re­port of the pre­clin­i­cal safe­ty find­ings was pre­sent­ed to the AveX­is safe­ty man­age­ment team last March and the com­pa­ny “de­ter­mined at that time that the safe­ty find­ing should be in­clud­ed in the an­nu­al up­date of the in­ves­ti­ga­tor brochure planned for Sep­tem­ber 2019. Un­for­tu­nate­ly, a mis­take was made, and this up­date was not im­ple­ment­ed.”

The omis­sion was lat­er iden­ti­fied as part of a No­var­tis re­view re­lat­ed to the Form 483 re­sponse from Au­gust, and the spokesper­son told Fo­cus, “This omis­sion was iden­ti­fied and the is­sue quick­ly as­sessed and man­aged pur­suant to ex­ist­ing No­var­tis safe­ty process­es and we no­ti­fied health au­thor­i­ties and clin­i­cal tri­al in­ves­ti­ga­tors.”

But the spokesper­son al­so said that No­var­tis no­ti­fied in­ves­ti­ga­tors and the FDA at the end of last week on the find­ings and was no­ti­fied about the par­tial clin­i­cal hold ear­li­er this week.

The com­pa­ny al­so stressed that the par­tial hold does not im­pact the mar­ket­ing of Zol­gens­ma or some oth­er clin­i­cal tri­als.

“This was a small, AveX­is-ini­ti­at­ed pre-clin­i­cal study in which an­i­mal find­ings showed dor­sal root gan­glia (DRG) mononu­clear cell in­flam­ma­tion, some­times ac­com­pa­nied by neu­ronal cell body de­gen­er­a­tion or loss. The tri­al in­volved 12 non-hu­man pri­mates,” the No­var­tis spokesper­son said.

The clin­i­cal sig­nif­i­cance of the DRG in­flam­ma­tion ob­served in this pre-clin­i­cal an­i­mal study is not known and was not seen in pri­or an­i­mal stud­ies, the com­pa­ny added. “We will con­tin­ue to close­ly mon­i­tor for any re­ports of re­lat­ed safe­ty events in pa­tients,” No­var­tis said. “We will work dili­gent­ly with FDA to iden­ti­fy any ad­di­tion­al ac­tions nec­es­sary to re­sume dos­ing in the AVXS-101 in­trathe­cal clin­i­cal tri­als.”

In Au­gust, No­var­tis ran in­to trou­ble with the FDA when da­ta ma­nip­u­la­tion was un­cov­ered in the Zol­gens­ma ap­pli­ca­tion, al­though the ma­nip­u­la­tion did not af­fect the FDA’s as­sess­ment of the gene ther­a­py’s safe­ty or ef­fi­ca­cy. Ques­tions re­lat­ed to the time­line of the un­cov­er­ing of the ma­nip­u­la­tion were al­so raised.


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Mi­no­ryx and Sper­o­genix ink an ex­clu­sive li­cense agree­ment to de­vel­op and com­mer­cial­ize lerigli­ta­zone in Chi­na

September 23, 2020 – Hong Kong, Beijing, Shanghai (China) and Mataró, Barcelona (Spain)  

Minoryx will receive an upfront and milestone payments of up to $78 million, as well as double digit royalties on annual net sales 

Sperogenix will receive exclusive rights to develop and commercialize leriglitazone for the treatment of X-linked adrenoleukodystrophy (X-ALD), a rare life-threatening neurological condition

Vas Narasimhan (AP Images)

UP­DAT­ED: Still held down by clin­i­cal hold, No­var­tis' Zol­gens­ma falls fur­ther be­hind Bio­gen and Roche as FDA asks for a new piv­otal study

Last October, the FDA slowed down Novartis’ quest to extend its gene therapy to older spinal muscular atrophy patients by slapping a partial hold on intrathecal administration. Almost a year later, the hold is still there, and regulators are adding another hurdle required for regulatory submission: a new pivotal confirmatory study.

The new requirement — which departs significantly from Novartis’ prior expectations — will likely stretch the path to registration beyond 2021, when analysts were expecting a BLA submission. That could mean more time for Biogen to reap Spinraza revenues and Roche to ramp up sales of Evrysdi in the absence of a rival.

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FDA commissioner Stephen Hahn at the White House (AP Images)

Un­der fire, FDA to is­sue stricter guid­ance for Covid-19 vac­cine EUA this week — re­port

The FDA has been insisting for months that a Covid-19 vaccine had to be at least 50% effective – a measure of transparency meant to shore public trust in the agency and in a vaccine that had been brought forward at record speed and record political pressure. But now, with concerns of a Trump-driven authorization arriving before the election, the agency may be raising the bar.

The FDA is set to release new guidance that would raise safety and efficacy requirements for a vaccine EUA above earlier guidance and above the criteria used for convalescent plasma or hydroxychloroquine, The Washington Post reported. Experts say this significantly lowers the odds of an approval before the election on November 3, which Trump has promised despite vocal concerns from public health officials, and could help shore up public trust in the agency and any eventual vaccine.

David Berry (Flagship)

Flag­ship's next big tech­no­log­i­cal bet? The cloud

Earlier this month, Flagship announced their big bet on the software half the industry is talking about, launching the AI and machine learning startup. Now, they and a couple other investors are gambling $100 million on a software that much of the public generally thinks of as a cool, IT afterthought: cloud computing.

The idea, says founder and Flagship partner David Berry, is one of scale: The sheer magnitude of biological data that you can store on cloud technology is unprecedented. And that size, when leveraged properly, can allow you to ask questions and form insights that are similarly unprecedented.

Jim Roberts and Brian Finrow (Lumen Bioscience)

With a $4M fed­er­al grant, Lu­men jumps in­to the Covid-19 treat­ment race

It’s been less than a month since Lumen Bioscience announced a $16 million Series B to engineer spirulina — a nutrient-packed super food — for diseases like traveler’s diarrhea, norovirus and C. difficile colitis. And now, the biotech has pulled in another $4 million to do the same for Covid-19.

The approach is quite similar to other gastrointestinal targets the company is pursuing, co-founders and Brian Finrow and Jim Roberts said. The Seattle-based company is working on a camelid antibody cocktail to combat GI infection common among Covid-19 patients. In a study published in the American Journal of Gastroenterology, a majority of Covid-19 patients showed GI and respiratory symptoms, and 25% had only GI symptoms.

CEO Markus Warmuth (Monte Rosa)

Monte Rosa rakes in $96M Se­ries B as it pre­pares 'mol­e­c­u­lar glue' plat­form for IND-en­abling stud­ies

About four months after completing an extension to its Series A, Monte Rosa Therapeutics is putting its next foot forward with another heap of cash.

The Boston-based biotech is back with $96 million in Series B financing with a goal to get its lead program ready for IND-enabling studies by the end of the year. Though Monte Rosa is keeping its specific target a secret for now, the company has been researching how to utilize its protein degradation technology in breast cancer and non-small cell lung cancer, among other areas.

Rep. Andy Harris (R-MD) (Tasos Katopodis/Pool via AP Images)

The mi­cro-cap that tapped a mask-skep­tic con­gress­man for their Covid DSMB is ap­ply­ing for an EUA. Their ev­i­dence? 21 pa­tients

NeuroRx, the tiny biotech that came under fire last week after Politico reported they selected a congressman and two other acquaintances of the CEO to supervise their Covid-19 drug trial, announced today that they will ask the FDA to authorize their drug based on the results of just 21 patients.

Such an application would test the agency’s standards of evidence for an EUA, which have already come under scrutiny after controversial authorizations for convalescent plasma and hydroxychloroquine. The only other company to discuss their intention to file for an EUA, Eli Lilly, did so after results came back from a randomized control study testing their antibody in over 450 patients.

PhII Alzheimer's fail­ure deals new blow to Roche, AC Im­mune — but the tau hy­poth­e­sis is far from dead

The leading anti-tau antibody has failed its first Phase II testing, casting a shadow on a popular target (just trailing amyloid beta) for Alzheimer’s disease.

Roche and AC Immune are quick to acknowledge disappointment in the topline readout, which suggested that semorinemab did not reduce cognitive decline among patients with early Alzheimer’s disease, who are either just starting to have symptoms or have mild manifestations.

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Covid-19 roundup: J&J be­gins piv­otal Phase III tri­al for vac­cine; Con­tro­ver­sial hu­man chal­lenge tri­als to be­gin in Lon­don — re­port

Johnson & Johnson announced it’s beginning a pivotal Phase III trial for its Covid-19 candidate, JNJ-78436735 — the first single-dose vaccine in this stage.

The Phase III trial, dubbed ENSEMBLE, will enroll 60,000 patients worldwide, making it the largest Phase III study of a Covid-19 vaccine to date. J&J said the candidate achieved positive interim results in a Phase I/IIa study, which will be published “imminently.” There’s a possibility that the first batches will be ready for potential emergency use in early 2021, according to the company.

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