#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.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

So — that pig-to-hu­man trans­plant; Po­ten­tial di­a­betes cure reach­es pa­tient; Ac­cused MIT sci­en­tist lash­es back; 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.

We’re incredibly excited to welcome Beth Bulik, seasoned pharma marketing reporter, to the team. You can find much of her work in our new Marketing channel — and in her weekly newsletter, Endpoints PharmaRx, which will launch in early November. Add it to your subscriptions here.

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NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty

 

I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

Marty Duvall, Oncopeptides CEO

On­copep­tides stock craters as it pulls can­cer drug Pepax­to from the mar­ket

Shares of Oncopeptides crashed more than 70% in early Friday trading after the company said it’s pulling its multiple myeloma drug Pepaxto (melphalan flufenamide) from the US market after failing a confirmatory trial. The move will force the company to close its US and EU business units and enact significant layoffs.

The FDA had scheduled an adcomm meeting next Thursday to discuss Pepaxto, which first won accelerated approval in February and costs about $19,000 per course of treatment. The committee was to weigh in on whether the confirmatory trial demonstrated a worse overall survival in the treatment arm compared to the control arm.

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Bris­tol My­ers pledges to sell its Ac­celeron shares as ac­tivist in­vestors cir­cle Mer­ck­'s $11.5B buy­out — re­port

Just as Avoro Capital’s campaign to derail Merck’s proposed $11.5 billion buyout of Acceleron gains steam, Bristol Myers Squibb is leaning in with some hefty counterweight.

The pharma giant is planning to tender its Acceleron shares, Bloomberg reported, which add up to a sizable 11.5% stake. Based on the offer price, the sale would net Bristol Myers around $1.3 billion.

To complete its deal, Merck needs a majority of shareholders to agree to sell their shares.