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.

Com­mu­ni­cat­ing the val­ue of pre­ci­sion med­i­cine

By Natasha Cowan, Content Marketing Manager at Blue Latitude Health.
Many stakeholders are confused by novel precision medicines, including patients and healthcare professionals. So, how can industry help them to navigate this complexity?

Precision medicine represents a new paradigm in healthcare. It embodies the shift from treating many patients with the same therapy, to having the tools to identify the best treatment for every patient.

Spe­cial re­port: Twen­ty ex­tra­or­di­nary women in bio­phar­ma R&D who worked their way to the top

What differentiates a woman leader in biopharma R&D from a man?

Not much, except there are fewer of them in senior posts. Data suggest women are not more risk-averse, family-oriented or less confident than their male counterparts — indeed the differences between the two sexes are negligible. But a glance at the top R&D positions in Big Pharma leaves little doubt that upward migration in the executive ranks of biopharma R&D is tough.

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Ed­i­tas and Cel­gene sub Juno are tack­ling hottest im­munother­a­py cells

As the first CRISPR-edited cancer patients watch their treatments unfold, one of the first CRISPR companies is rejigging a major oncology deal.

Editas Medicine is amending its long-running collaboration with Celgene and their subsidiary Juno Therapeutics. The new deal will expand the focus of their work to cover a subset of immune cells that have become an increasingly hot target for immunotherapy: gamma-delta cells.

FDA Vas­cepa re­view spot­lights new safe­ty sig­nals, pos­si­ble min­er­al oil spoil­er as Amarin hunts a block­buster ap­proval

An in-house FDA review of Amarin’s Vascepa raises a set of hurdles the biotech will have to clear if the biotech expects to get the long-awaited FDA approval that could set it on a path to superstar status. But it appears that Amarin has survived another potential setback without introducing a major new threat to its prospects.
The stakes don’t get much higher, with analysts saying a win this week for Amarin could lead to billions in new sales — provided the agency stamps it with an OK. And investors liked what they say in the FDA review this morning, bumping the stock $AMRN 17%.
The insider take at the agency includes a note on two new safety signals seen in the big cardio outcomes study of the omega-3 fatty acid drug that shocked many analysts with a solid set of efficacy data. There’s a key concern over whether the use of mineral oil in the placebo skewed LDL levels in such a way that tilted the data in Amarin’s favor.
The FDA overview was written by John Sharretts, the acting deputy director in the Division of Metabolism and Endocrinology Products. 
On the safety side, the internal review focused on a 3.1% versus 2.1% rate of adjudicated events of atrial fibrillation or atrial flutter requiring hospitalization. But they also say a-fib shouldn’t confound the benefit-safety of the drug — given the improvement on MACE — or prevent its use. And then there was also a higher rate of bleeding events in the drug arm.

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Prakash Raman. Flagship

Flag­ship woos No­var­tis top deal­mak­er Prakash Ra­man in move to get the BD ball rolling ear­ly

Flagship Pioneering likes to be ahead of its times — so far ahead, perhaps, that it is often challenging to find partners for their startups while the scientific scaffolding is underway. But Prakash Raman is here to change that.

Raman, who most recently headed up business development at the Novartis Institutes for BioMedical Research, became Flagship’s first chief business development officer two weeks ago. By acting as a “central resource” for the 100 companies in the venture fund’s portfolio, he hopes to help entrepreneurs and management teams strategize about dealmaking to capture value beyond the near-term validation of their platform technologies, Raman told Endpoints News.

FDA puts Sol­id Bio’s lead gene ther­a­py pro­gram on hold — again — af­ter an­oth­er pa­tient is hurt by SGT-001

Solid Biosciences continues to be plagued by safety issues.

Close to 18 months after the gene therapy biotech was able to quickly shed an FDA hold on their lead Duchenne muscular dystrophy program for SGT-001, regulators have stepped back in to force another halt after another patient was hit hard by a set of serious adverse events remarkably similar to the first set.

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Bill Haney, Skyhawk

Cel­gene ex­ecs shell out $92M cash for a pair of R&D deals that will fit per­fect­ly in their new home at Bris­tol-My­ers

With Bristol-Myers Squibb’s Celgene buyout all but complete, the BD teams are working in perfect synchrony now. The Celgene side is going back to Skyhawk, a darling of the crowd that set out to drug RNA, and they’re adding a suite of new programs that mesh perfectly with the new regime in charge.

Celgene is shelling out $80 million in a cash upfront to add oncology, immuno-oncology and autoimmune diseases to the initial roundup of neurological targets mapped early in Skyhawk’s existence.

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Reata's bar­dox­olone of­fers promise in pa­tients with rare kid­ney dis­or­der

After surprising Wall Street with positive data on its drug, omaveloxolone, in patients suffering from a notoriously hard-to-treat degenerative neuromuscular disorder last month, Reata Pharma on Monday unveiled pivotal results from a trial testing another drug, bardoxolone, in patients with a rare, genetic form of chronic kidney disease for which there exist no approved therapies.

Bardoxolone, like Reata’s other lead drug — omaveloxolone — is a small molecule engineered to bind to a gene called Keap1 to enhance the activity of the protein Nrf2 in order to defuse inflammation.

Am­gen ax­es 149 of its staff in Cam­bridge of­fice; Evotec, Mil­li­pore­Sig­ma en­ter re­search pact

→ Amgen has submitted a Worker Adjustment and Retraining Act (WARN) — a warning of impending mass layoffs 60 days in advance of the date — to the state of Massachusetts in the wake of the company’s exodus from the neurosciences R&D sector. David Reese, the company’s R&D chief, said at the time that the company is cutting ties in the field to focus on other undisclosed areas. In its WARN notice, the Cambridge-based company stated that 149 of its employees would be affected — among the total 180 being let go. The terminations will take effect on December 31, 2019.