FDA to Aveo: That's still a 'no' on ti­vo. Aveo: We'll be back.

In the nev­er-end­ing but hard­ly-chang­ing saga of the FDA and Aveo On­col­o­gy, the US reg­u­la­tor has once again spurned the com­pa­ny for fail­ing to prove that their drug helped re­nal cell car­ci­no­ma pa­tients live longer.

Aveo an­nounced this morn­ing that the FDA rec­om­mend­ed they not sub­mit an NDA ap­pli­ca­tion be­cause the lat­est Phase III tri­al da­ta don’t al­lay the agency’s con­cern that their drug, tivozanib, is hurt­ing pa­tients, as com­pared with the base­line treat­ment, Bay­er’s so­rafenib. Once again, the con­cern is about the over­all sur­vival rate.

“The FDA not­ed that the Com­pa­ny’s cur­rent in­ter­im OS re­sults do not ab­ro­gate the FDA’s con­cerns over detri­ment and that those re­sults may wors­en with fi­nal analy­sis at 263 events, and that the me­di­an OS for tivozanib is worse than that of so­rafenib,” Aveo wrote.

In re­sponse, Aveo said it will nar­row its pro­posed in­di­ca­tion to re­lapsed/re­frac­to­ry re­nal cell car­ci­no­ma, with plans to sub­mit an NDA in the first quar­ter of 2020. But they agreed with the agency that if in the fi­nal analy­sis, the over­all sur­vival haz­ard ra­tio is over 1.00 – if peo­ple are more like­ly to die in the tivozanib arm– they will with­draw their NDA. In Aveo’s telling, the reg­u­la­tors don’t sound op­ti­mistic about Aveo’s rec­om­men­da­tion.

Michael Bai­ley

“At the meet­ing, the FDA ac­knowl­edged AVEO’s re­spons­es and re­it­er­at­ed its con­cerns about the sur­vival in­for­ma­tion and the to­tal­i­ty of da­ta,” Aveo wrote. “The FDA not­ed that the choice to sub­mit the da­ta is the Com­pa­ny’s, and that a dis­cus­sion with the On­co­log­ic Drug Ad­vi­so­ry Com­mit­tee will like­ly be re­quired.”

The news sent Aveo’s stock plum­met­ing deep­er in­to pen­ny stock ter­ri­to­ry, down 30% to $0.62 per share.

The FDA first re­buffed Aveo in 2013 at the end of their first Phase III tri­al, af­ter the agency raised con­cerns about the sur­vival rate and ex­perts on the re­view pan­el ex­pressed out­rage at the tri­al de­sign and dis­ap­point­ment over the pro­posed la­bel.  Most no­tably, the agency said the drug im­proved dis­ease-free pro­gres­sion by 20%, but al­so in­creased the risk of death by 25%.

“If we ap­prove this drug based on this study how would we com­mu­ni­cate to pa­tients the po­ten­tial 25 per­cent in­crease in the risk of death?” Jonathan Jarow, then-med­ical of­fi­cer at the FDA, asked the pan­el, per Reuters. The pan­el vot­ed 13-1 against the drug, and the FDA re­ject­ed it.

The FDA had, in fact, al­ready rec­om­mend­ed a new tri­al, an SEC in­ves­ti­ga­tion would lat­er al­lege, and Aveo failed to no­ti­fy in­vestors of that fact – even­tu­al­ly lead­ing to ex­ec­u­tive res­ig­na­tions and a $4 mil­lion set­tle­ment.

Aveo is now near­ing the end of its sec­ond tri­al, ti­tled TI­VO-3, and still has not al­layed FDA con­cerns. They did man­age to con­vince the EMA in 2017 to ap­prove tivozanib for re­nal cell car­ci­no­ma but with the caveat that the Eu­ro­pean agency would re­view the TI­VO-3 re­sults as part of its post-mar­ket­ing re­quire­ments.

That ap­proval is al­so at risk. Af­ter Aveo’s first re­leased pre­lim­i­nary da­ta for Ti­vo-3 last No­vem­ber, re­veal­ing an OS HR of 1.12, the EMA warned “reg­u­la­to­ry ac­tion” was pos­si­ble if an Au­gust in­ter­im analy­sis didn’t yield a bet­ter over­all sur­vival rate. The Au­gust num­ber, HR 0.99, wasn’t enough for the FDA. It re­mains to be seen what the EMA thinks — and what the fi­nal re­sults will be.

Vac­cine doc­u­ments, young lead­ers and mar­ket tur­moil: End­points' 10 biggest sto­ries of 2022

It’s been a volatile year in the world of biopharma. Market declines reset M&A valuations, and may be beginning to tempt bigger buyers back into dealmaking. Russia’s war in Ukraine disrupted drug sales and clinical trials. A new generation of young biotech leaders emerged in the Endpoints 20(+1) Under 40. And as capital runs dry in a tough environment for raising new funds, companies big and small are taking a look at their headcounts and operations for ways to make it through lean times.

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Tom Riga, Spectrum Pharmaceuticals CEO

Spec­trum im­plodes af­ter a harsh pub­lic slap­down and now a CRL from Richard Paz­dur

The FDA has gone out of its way several times to flatten any expectations for Spectrum’s lung cancer drug poziotinib, including slamming the regulatory door in the biotech’s face four years ago when the their executive crew came calling for a breakthrough drug designation and encouragement from the oncology wing of the FDA.

That stinging early rebuke pointed straight down the path to a corrosive in-house agency review of Spectrum’s attempt to land an accelerated approval for the oral EGFR TKI and a public whipping that included a classic takedown by none other than Richard Pazdur, who slammed the company for “poor drug development” that led to confusion over the dose needed for a slice of NSCLC patients harboring HER2 exon 20 insertion mutations.

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Big Phar­ma's Twit­ter ex­o­dus; Mer­ck wa­gers $1.35B on buy­out; $3.5M gene ther­a­py; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

As you start planning for #JPM23, we hope you will consider joining Endpoints News for our live and virtual events. For those who are celebrating Thanksgiving, we hope you are enjoying the long weekend with loved ones. And if you’re not — we’ll see you next week!

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Robert Califf, FDA commissioner (Jose Luis Magana/AP Images)

Fourth ac­cel­er­at­ed ap­proval in Duchenne? Sarep­ta gets pri­or­i­ty re­view for gene ther­a­py amid FDA scruti­ny

Sarepta is once again on the accelerated approval path for a Duchenne drug, picking up a priority review Monday morning.

The FDA granted the accelerated review to SRP-9001, Sarepta announced Monday, which would become the biotech’s fourth Duchenne drug if approved. Much like SRP-9001 will do, each of the previous three therapies went through the accelerated approval pathway. But unlike the others, SRP-9001 is a gene therapy.

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Albert Bourla, Pfizer CEO (John Thys/POOL/AFP via Getty Images)

Pfiz­er CEO un­der fire from UK watch­dog over vac­cine com­ments — re­port

Pfizer CEO Albert Bourla told the BBC last December that he had “no doubt in my mind that the benefits, completely, are in favor” of vaccinating 5- to 11-year-olds for Covid-19. Almost a year later, those comments have reportedly landed him in trouble with a UK pharma watchdog.

Children’s advocacy group UsForThem filed a complaint with the UK’s Prescription Medicines Code of Practice Authority (PMCPA) last year accusing Bourla of making “disgracefully misleading” statements during the BBC interview, including one that “Covid in schools is thriving.” At the time, UK regulators had not yet cleared the vaccine for the 5 to 11 age group, though the vaccine did have a positive opinion from the EMA’s human medicines committee.

Sanofi's new headquarters, La Maison Sanofi, in Paris (Credit: Luc Boegly)

Sanofi wel­comes 500 staffers to new Paris HQ af­ter €30M ren­o­va­tion

When Paul Hudson took the helm at Sanofi back in 2019, he promised to reinvent the pharma giant — including its Paris headquarters. This week, the company set up shop in new “state-of-the-art” digs.

La Maison Sanofi, as the new HQ is called, is officially open for business, Hudson announced on Monday. The 9,000-square-meter (just under 97,000-square-foot) space accommodates 500 employees across the company’s government and global support functions teams, including finance, HR, legal and corporate affairs — and it was built with environmental sustainability and hybrid work in mind.

Sta­da to place $50M+ in­vest­ment in a new fa­cil­i­ty in Ro­ma­nia

While Romania may conjure up images of vast mountain ranges and tales of medieval kings, one generic manufacturer has broken ground on a new facility there.

German pharma company Stada said Monday that it has placed a €50 million ($51.9 million) investment into a 100,000 square-meter (1.08 million square-foot) site in Turda, Romania, a city in the Southeast of the country. According to a Stada spokesperson in an email to Endpoints News, the company has developed only 281,500 square feet of the site so far.

Rachael Rollins (Charles Krupa/AP Images)

US seeks jail time for co-CEO of New Eng­land com­pound­ing cen­ter af­ter dead­ly 2012 fun­gal out­break

The US attorney for the district of Massachusetts late last week called on the state’s district court to sentence the former co-owner of the now-defunct New England Compounding Center to 18 months of jail time for his role in the center’s quality deviations that led to more than 100 people dead from a fungal meningitis outbreak.

Gregory Conigliaro was convicted of conspiring with more than a dozen others at NECC to deceive the FDA and misrepresent the fact that the center was only dispensing drugs pursuant to patient-specific prescriptions.

FDA tells Catal­ent to fix is­sues at two man­u­fac­tur­ing sites on its own

The CDMO Catalent will have to fix issues at two manufacturing plants in the US and Europe that were subject to inspections by the FDA this summer, giving the company room to correct the issues without facing further regulatory action.

The FDA gave Catalent a “voluntary action indicated” response to two inspections at the contract manufacturer’s site in Bloomington, IN, and Brussels, Belgium. Fixing the issues on its own is a preferable outcome to facing an “official action indicated” response, meaning that an official warning would be sent out or a sit-down with the FDA would be required.

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