#ES­MO20: As­traZeneca bur­nish­es Tagris­so's ad­ju­vant NSCLC pro­file with 'un­prece­dent­ed' re­duc­tion in brain mets. Can they win over skep­tics?

When As­traZeneca trum­pet­ed “mo­men­tous” and “trans­for­ma­tive” re­sults for Tagris­so ear­li­er this year at AS­CO, some prac­ti­tion­ers threw cold wa­ter on the ADAU­RA fer­vor. Sure, the dis­ease-free sur­vival da­ta look good, but over­all sur­vival is the end­point that mat­ters when it comes to choos­ing ad­ju­vant ther­a­py for non-small cell lung can­cer pa­tients, the ex­perts said.

The OS da­ta still aren’t here, but As­traZeneca is back at ES­MO to bol­ster their case with a look at brain metas­ta­sis da­ta.

José Basel­ga

EGFR-mu­tant NSCLC fre­quent­ly goes to the brain, with a re­cur­rence rate as high as 40% in some stud­ies, can­cer R&D chief José Basel­ga ex­plained, and it’s “one of the most dev­as­tat­ing com­pli­ca­tions” for this group of pa­tients. While Tagris­so’s abil­i­ty to cross the blood-brain bar­ri­er find­ings gave them hope that it could have an ef­fect here, he not­ed the find­ings were “quite dra­mat­ic.”

Look­ing at pa­tients who were di­ag­nosed at an ear­ly stage and had surgery to re­sect their tu­mors, Tagris­so cut the risk of CNS re­cur­rence or death by 82%, trans­lat­ing to a haz­ard ra­tio of 0.18 com­pared with place­bo (p<0.0001).

At the three-year fol­low-up, Basel­ga added, 98% of pa­tients in the Tagris­so arm are free of brain metas­tases.

“This is to­tal­ly un­prece­dent­ed,” he told End­points News in a pre­view.

While ac­knowl­edg­ing that com­ments on the need for OS da­ta are “ab­solute­ly ap­pro­pri­ate,” he said what is al­ready known should be suf­fi­cient to con­vince physi­cians to change their prac­tice.

The ADAU­RA da­ta pre­sent­ed at AS­CO marked “the most pos­i­tive study in the his­to­ry of ad­ju­vant ther­a­py” in this par­tic­u­lar space, he said.

“I mean — it’s in­cred­i­bly com­pelling,” he said. “As a treat­ing physi­cian, I would not imag­ine how I can not of­fer this to a pa­tient. I think this in my mind clear­ly re­in­forces that it’s a new stan­dard of care in a very pow­er­ful way.”

As­traZeneca’s goal here has been to po­si­tion Tagris­so as an al­ter­na­tive or ad­di­tion to chemother­a­py that can give pa­tients more time, post-op­er­a­tion, liv­ing can­cer-free.

At AS­CO it show­cased a win on dis­ease-free sur­vival among pa­tients with Stage II and II­IA dis­ease, the pri­ma­ry end­point of ADAU­RA, which was big enough to war­rant an ear­ly stop to the tri­al. It achieved a 83% re­duc­tion in risk of dis­ease re­cur­rence or death, in­ves­ti­ga­tors re­port­ed then. But with­out OS da­ta, lung can­cer ex­pert Jack West cau­tioned, you can’t rule out the pos­si­bil­i­ty that pa­tients would do just as well get­ting treat­ed at re­lapse rather than stay­ing on Tagris­so the whole time.

Skep­tics will still have ques­tions, but the next big move lies with the FDA. Reg­u­la­tors grant­ed break­through ther­a­py des­ig­na­tion in Ju­ly, boost­ing As­traZeneca’s hopes of mov­ing Tagris­so — cur­rent­ly ap­proved as a front­line treat­ment — to an even ear­li­er line.

Charles Baum, Mirati CEO

Mi­rati plots a march to the FDA for its KRAS G12C drug, breath­ing down Am­gen’s neck with bet­ter da­ta

Mirati Therapeutics $MRTX took another closely-watched step toward a now clearly defined goal to file for an approval for its KRAS G12C cancer drug adagrasib (MRTX849), scoring a higher response rate than the last readout from the class-leading rival at Amgen but still leaving open a raft of important questions about its future.

Following a snapshot of the first handful of responses, where the drug scored a tumor response in 3 of 5 patients with non-small cell lung cancer, the response rate has now slid to 45% among a pooled group of 51 early-stage and Phase II patients, 43% — 6 of 14 — when looking solely at the Phase I/Ib. Those 14 patients had a median treatment duration of 8.2 months, with half still on therapy and 5 of 6 responders still in response.

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In his­toric Covid-19 ad­comm, vac­cine ex­perts de­bate a sea of ques­tions — but of­fer no clear an­swers

The most widely anticipated and perhaps most widely watched meeting in the FDA’s 113-year history ended late Thursday night with a score of questions and very few answers.

For nearly 9 hours, 18 different outside experts listened to public health agencies and foundations present how the United States’ Covid-19 vaccine program developed through October, and they debated where it should go from there: Were companies testing the right metrics in their massive trials? How long should they track patients before declaring a vaccine safe or effective? Should a vaccine, once authorized, be given to the volunteers in the placebo arm of a trial?

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Michel Vounatsos, Biogen CEO (via YouTube)

Bio­gen spot­lights a pair of painful pipeline set­backs as ad­u­canum­ab show­down looms at the FDA

Biogen has flagged a pair of setbacks in the pipeline, spotlighting the final failure for a one-time top MS prospect while scrapping a gene therapy for SMA after the IND was put on hold due to toxicity.

Both failures will raise the stakes even higher on aducanumab, the Alzheimer’s drug that Biogen is betting the ranch on, determined to pursue an FDA OK despite significant skepticism they can make it with mixed results and a reliance on post hoc data mining. And the failures are being reported as Biogen was forced to cut its profit forecast for 2020 as a generic rival started to erode their big franchise drug.

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Biond­Vax stock im­plodes af­ter a big PhI­II gam­ble for its uni­ver­sal flu vac­cine fails

After flying high on Wall Street for the last few months of a pandemic, BiondVax’s stock and dreams of getting approval for its universal flu vaccine hit the windshield.

The Jerusalem-based biotech announced on Friday that its only clinical candidate, M-001, failed both primary and secondary endpoints in a Phase III study. There was no statistically significant difference in reduction of flu illness and severity between the vaccine and placebo groups, according to the company. The vaccine did prove safe, if ineffective, BiondVax said.

A top drug pro­gram at Bay­er clears a high bar for CKD — open­ing the door to an FDA pitch

Over the past 4 years, Bayer has been steering a major trial through a pivotal program to see if their drug finerenone could slow down the pace of chronic kidney disease in patients suffering from both CKD as well as Type 2 diabetes.

Today, their team jumped on a virtual meeting hosted by the American Society of Nephrology to offer a solid set of pivotal data to demonstrate that the drug can delay dialysis or a kidney replacement as well as cardio disease, while also adding some worrying signs of hyperkalemia among the patients taking the drug. And they’re hustling it straight to regulators in search of an approval for kidney disease and cardio patients — one of the toughest challenges in the book, as demonstrated by repeated past failures.

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Dan O'Day, Gilead CEO (Andrew Harnik, AP Images)

UP­DAT­ED: FDA anoints Gilead­'s remde­sivir as the Covid-19 treat­ment win­ner, hand­ing down full ap­proval — de­spite some deep skep­ti­cism

Seven months into the Covid-19 pandemic, the race to develop a treatment for the disease that’s proved to be the biggest health crisis in a century has an officially designated winner: Gilead. And they’re picking up the prize — worth billions in peak sales — despite a major study that concluded the drug was no help in reducing the number of people who die from the virus.

The FDA handed down a thumbs-up for remdesivir, the company announced Thursday afternoon, as the drug becomes the first fully approved treatment for Covid-19 in the US. Remdesivir, to be marketed as Veklury, will come with a label for treatment in adults and children older than 12 in Covid-19 cases that require hospitalization.

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Stephen Hahn, FDA commissioner (AP Images)

As FDA sets the stage for the first Covid-19 vac­cine EUAs, some big play­ers are ask­ing for a tweak of the guide­lines

Setting the stage for an extraordinary one-day meeting of the Vaccines and Related Biological Products Advisory Committee this Thursday, the FDA has cleared 2 experts of financial conflicts to help beef up the committee. And regulators went on to specify the safety, efficacy and CMC input they’re looking for on EUAs, before they move on to the full BLA approval process.

All of this has already been spelled out to the developers. But the devil is in the details, and it’s clear from the first round of posted responses that some of the top players — including J&J and Pfizer — would like some adjustments and added feedback. And on Thursday, the experts can offer their own thoughts on shaping the first OKs.

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CRISPR Ther­a­peu­tics gets a snap­shot of off-the-shelf CAR-T suc­cess in B-cell ma­lig­nan­cies — marred by the death of a pa­tient

Just days after scientific founder Emmanuelle Charpentier shared the Nobel prize for her work on CRISPR/Cas9, CRISPR Therapeutics $CRSP is showing off a snapshot of success in their early-stage study for an off-the-shelf CAR-T approach to CD19+ B cell malignancies — a snapshot marred by the death of a patient who had been given a high dose of the treatment.

Using their gene editing tech, researchers for CRISPR engineered cells from healthy donors into an attack vehicle aimed at cancer, something that has been achieved with great success using patients’ own cells — the autologous approach. But autologous CAR-T is hampered by the more complex vein-to-vein requirement that delays treatment, and now CRISPR Therapeutics along with other players like Allogene are determined to replace the pioneers with CAR-T 2.0.

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Pascal Soriot, AstraZeneca CEO (Zach Gibson/Bloomberg via Getty Images)

UP­DAT­ED: FDA gives As­traZeneca the thumbs-up to restart PhI­II Covid-19 vac­cine tri­als, and J&J is prepar­ing to re­sume its study

Several countries had restarted their portions of AstraZeneca’s global Phase III Covid-19 vaccine trial after the study was paused worldwide in early September, but the US notably stayed on the sidelines — until now. Friday afternoon the pharma giant announced the all clear from US regulators. And on top of that, J&J announced Friday evening that it’s preparing to resume its own Phase III vaccine trial.