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.

Grow­ing ac­cep­tance of ac­cel­er­at­ed path­ways for nov­el treat­ments: but does reg­u­la­to­ry ap­proval lead to com­mer­cial suc­cess?

By Mwango Kashoki, MD, MPH, Vice President-Technical, and Richard Macaulay, Senior Director, of Parexel Regulatory & Access

In recent years, we’ve seen a significant uptake in the use of regulatory options by companies looking to accelerate the journey of life-saving drugs to market. In 2018, 73% of the novel drugs approved by the U.S. Federal Drug Administration (FDA) were designated under one or more expedited development program categories (Fast Track, Breakthrough Therapy, Priority Review, and Accelerated Approval).ᶦ

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Anthony Fauci (AP Images)

UP­DAT­ED: NIH-part­nered Mod­er­na ships off its PhI-ready coro­n­avirus vac­cine can­di­date to a sea of un­cer­tain­ty

Off it goes.

Moderna has shipped the first batch of its mRNA vaccine against SARS-CoV-2 from its manufacturing facility in Norwood, Massachusetts, to the National Institute of Allergy and Infectious Diseases in Bethesda, Maryland, for a pioneering Phase I study.

It’s a hectic race against time. In the 42 days since Moderna selected the sequence they would use to develop their vaccine — a record time, no less — the number of confirmed cases around the world has surged astronomically from a few dozen to over 80,000, per WHO and Johns Hopkins estimates.

The candidate that they came up with, mRNA-1273, encodes for a prefusion stabilized form of the spike protein, which gives the virus its crown shape and plays a key role in transmission. The Coalition for Epidemic Preparedness Innovations, the Oslo-based group better known as CEPI, funded the manufacture of this batch.

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In fi­nal re­port, ICER ap­pears to have a change of heart on new acute mi­graine ther­a­pies

ICER appears to have reversed course on the fresh crop of acute migraine therapies.

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When drug val­ue as­sess­ment meets re­al-world ev­i­dence: ICER en­lists Ae­tion in pric­ing eval­u­a­tion

In a union of two of the hottest trends in the US biopharma world, ICER is teaming up with a high-profile company to integrate real-world evidence in their assessment of treatment value.

The drug pricing watchdog — formally the Institute for Clinical and Economic Review — said it will utilize Aetion’s evidence platform in “select upcoming assessments” and their new 24-month re-evaluations of drugs granted accelerated approval by the FDA.

Anthony Fauci, AP Images

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There are an estimated 50+ companies focused on developing drugs for non-alcoholic steatohepatitis, or NASH, a common liver disease that has long flummoxed researchers. The first wave of NASH drug developers struggled with efficacy as well as safety — and companies big and small have crashed and burned.

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