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.

Has the mo­ment fi­nal­ly ar­rived for val­ue-based health­care?

RBC Capital Markets’ Healthcare Technology Analyst, Sean Dodge, spotlights a new breed of tech-enabled providers who are rapidly transforming the way clinicians deliver healthcare, and explores the key question: can this accelerating revolution overturn the US healthcare system?

Key points

Tech-enabled healthcare providers are poised to help the US transition to value, not volume, as the basis for reward.
The move to value-based care has policy momentum, but is risky and complex for clinicians.
Outsourced tech specialists are emerging to provide the required expertise, while healthcare and tech are also converging through M&A.
Value-based care remains in its early stages, but the transition is accelerating and represents a huge addressable market.

Clay Siegall, Morphimmune CEO

Up­dat­ed: Ex-Seagen chief Clay Sie­gall emerges as CEO of pri­vate biotech

Clay Siegall will be back in the CEO seat, taking the helm of a private startup working on targeted cancer therapies.

It’s been almost a year since Siegall resigned from Seagen, the biotech he co-founded and led for more than 20 years, in the wake of domestic violence allegations by his then-wife. His eventual successor, David Epstein, sold the company to Pfizer in a $43 billion deal unveiled last week.

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Zhi Hong, Brii Biosciences CEO

Brii Bio­sciences stops man­u­fac­tur­ing Covid-19 an­ti­body com­bo, plans to with­draw EUA re­quest

Brii Biosciences said it will stop manufacturing its Covid-19 antibody combination, sold in China, and is working to withdraw its emergency use authorization request in the US, which it started in October 2021.

The Beijing and North Carolina biotech commercially launched the treatment in China last July but is now axing the work and reverting resources to other “high-priority programs,” per a Friday update. The focus now is namely hepatitis B viral infection, postpartum depression and major depressive disorders.

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Sergio Traversa, Relmada Therapeutics CEO

Rel­ma­da makes 'crit­i­cal changes' to PhI­II tri­al to try and save de­pres­sion drug

Relmada Therapeutics is making changes to its Phase III study of its lead drug for major depressive disorder, in an attempt to avoid problems with a prior trial that showed little difference between the drug and a placebo.

That failure in October wiped 80% from Relmada’s stock price, and was followed by another negative readout a few months later. In both cases, the company said that there had been trial sites that were associated with what it called surprising placebo effects that skewed the results compared with the drug, REL-1017.

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Peter Hecht, Cyclerion Therapeutics CEO

Hard pressed for cash, Cy­cle­ri­on looks for help fund­ing rare dis­ease drug

Cyclerion Therapeutics may have the design of a Phase IIb study ready to go, but it’s scrambling for a way to fund it.

The company said in a press release that it’s “actively evaluating the best combination of capital, capabilities, and transactions available to it to advance the development of zagociguat,” its lead candidate for a rare, genetic mitochondrial disease known as MELAS.

In a separate SEC filing, Cyclerion once again flagged “substantial doubt about (its) ability to continue as a going concern.” As of the end of 2022, it had cash and cash equivalents of only $13.4 million.

FDA ad­vi­sors unan­i­mous­ly rec­om­mend ac­cel­er­at­ed ap­proval for Bio­gen's ALS drug

A panel of outside advisors to the FDA unanimously recommended that the agency grant accelerated approval to Biogen’s ALS drug tofersen despite the drug failing the primary goal of its Phase III study, an endorsement that could pave a path forward for the treatment.

By a 9-0 vote, members of the Peripheral and Central Nervous System Drugs Advisory Committee said there was sufficient evidence that tofersen’s effect on a certain protein associated with ALS is reasonably likely to predict a benefit for patients. But panelists stopped short of advocating for a full approval, voting 3-5 against (with one abstention) and largely citing the failed pivotal study.

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Geoff McDonough, Generation Bio president and CEO

Mod­er­na part­ners on non-vi­ral gene ther­a­py with Gen­er­a­tion Bio af­ter swing­ing gene edit­ing deals

Moderna has inked a five-year partnership with gene therapy biotech Generation Bio, it announced Thursday morning, wading deeper into the genetic medicines space as it navigates beyond its vaccine work.

Moderna will pay Generation Bio $40 million upfront and invest another $36 million into the gene therapy biotech. In exchange, Moderna can license Generation Bio’s non-viral gene therapy platforms for two immune cell programs and two liver programs, with an option for a fifth program. Moderna will fund all the research work under the partnership, and could be on the hook for milestone, fee and royalty payments totaling up to $1.8 billion, a company spokesperson tells Endpoints News.

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Paul Song, NKGen Biotech CEO

NK cell ther­a­py-fo­cused biotech eyes SPAC deal

A small, Santa Ana-based biotech created in 2017 is looking to enter a SPAC deal as it lays out plans to begin trials in its lead cell therapy candidates and bring on new executives.

Graf Acquisition Corp. IV and NKGen Biotech announced Thursday, with few other details, that the two companies signed a non-binding letter of intent to “pursue a business combination.” Graf Acquisition II and III withdrew their IPOs last year.

In­cyte hit by CRL on ex­tend­ed-re­lease JAK tablets, mud­dy­ing plans for Jakafi fran­chise ex­pan­sion

The FDA has rejected Incyte’s extended-release formulation of ruxolitinib tablets, in a surprise setback for the company’s plans to build on its blockbuster Jakafi franchise.

The ruxolitinib XR tablets are designed to be taken once a day, whereas Jakafi is indicated for twice daily dosage (although some patients can take it once daily).

According to Incyte, the FDA acknowledged in its complete response letter that the study submitted in the NDA “met its objective of bioequivalence based on area under the curve (AUC) parameters but identified additional requirements for approval.”