Susan Galbraith, AstraZeneca oncology chief

Af­ter 18 years in de­vel­op­ment, As­traZeneca’s CT­LA-4 an­ti­body gets the red car­pet treat­ment at the FDA

Af­ter a decade, a sec­ond CT­LA-4 an­ti­body may fi­nal­ly be on its way to ap­proval.

As­traZeneca an­nounced Mon­day that the FDA had giv­en pri­or­i­ty re­view to treme­li­mum­ab, its long-ges­tat­ing CT­LA-4 an­ti­body, in com­bi­na­tion with the PD-L1 in­hibitor Imfinzi for pa­tients with liv­er can­cer that can’t be treat­ed with surgery.

The Big Phar­ma’s ap­pli­ca­tion is based on a mul­ti-year, 1,324-pa­tient study that showed 30.7% of pa­tients who re­ceived a “prim­ing dose” of treme­li­mum­ab fol­lowed by Imfinzi were alive af­ter three years, com­pared to 20.2% of pa­tients who re­ceived Bay­er’s so­rafenib, the stan­dard of care.

Su­san Gal­braith, As­traZeneca’s can­cer R&D chief, called that da­ta “un­prece­dent­ed.” Oth­ers raised ques­tions about how the da­ta held up com­pared to an al­ter­na­tive treat­ment reg­i­men be­ing de­vel­oped by Roche, and how much ben­e­fit the CT­LA-4 an­ti­body of­fered, giv­en that pa­tients who re­ceived Imfinzi alone showed near­ly iden­ti­cal sur­vival at the two-year mark. The dif­fer­ence on­ly emerged af­ter three years.

Nev­er­the­less, the three-year da­ta were no­table giv­en how oth­er PD-1 in­hibitors have done in the same set­ting when test­ed on their own. Op­di­vo failed to show an ad­van­tage over stan­dard of care in one tri­al, and Mer­ck has strug­gled to show that Keytru­da of­fers a mean­ing­ful ad­van­tage ei­ther.

Treme­li­mum­ab has had plen­ty of its own stum­bles. Pfiz­er first put the drug in tri­als in 2004, but aban­doned it soon af­ter, fol­low­ing dis­ap­point­ing ear­ly re­sults. It was still years be­fore Bris­tol My­ers Squibb showed block­ing CT­LA-4 could dra­mat­i­cal­ly ex­tend the lives of a sub­set of melanoma pa­tients, jump­start­ing the im­muno-on­col­o­gy field and mak­ing tens of bil­lions of dol­lars for Mer­ck and Bris­tol My­ers.

As­traZeneca li­censed Pfiz­er’s drug in 2011, hop­ing to get in on the still nascent im­muno-on­col­o­gy field, but it failed con­tin­u­al­ly in tri­als, in­clud­ing in lung, urothe­lial, and head and neck can­cer.

Al­though the drug would on­ly be OK’d for a lim­it­ed in­di­ca­tion, an ap­proval would make it the sec­ond CT­LA-4 an­ti­body on the mar­ket and the first con­tender to Bris­tol My­ers’ Yer­voy since it was ap­proved in 2011.

As­traZeneca is al­so hop­ing to get an ap­proval soon in com­bi­na­tion with Imfinzi in metasta­t­ic lung can­cer, al­though it is un­clear how much ben­e­fit the new drug of­fers over Imfinzi alone.

The Fac­tors Dri­ving a Rapid Evo­lu­tion of Gene & Cell Ther­a­py and CAR-T Clin­i­cal Re­search in APAC

APAC is the fastest growing region globally for cell & gene therapy trials representing more than a third of all cell & gene studies globally, with China leading in the region. 

APAC is the leading location globally for CAR-T trials with China attracting ~60% of all CAR-T trials globally between 2015-2022. The number of CAR-T trials initiated by Western companies has rapidly increased in recent years (current CAGR of about 60%), with multiple targets being explored including CD19, CD20, CD22, BCMA, CD30, CD123, CD33, CD38, and CD138.

The End­points 11; blue­bird's $3M gene ther­a­py; Bio­gen tout new neu­ro da­ta; Harsh re­views for can­cer drugs; 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.

Reading about John Carroll’s pick of biotech’s most promising startups has become a treasured tradition. If you ever get curious about previous classes of the Endpoints 11, you can find all of them (plus a number of our other regular specials) here.

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EMA warns of short­ages of two Boehringer heart drugs due to a spike in de­mand

The EMA is putting EU member states on alert over the shortage of two drugs that counter heart attacks due to an uptick in demand.

On Friday, the EMA sent out a warning that two Boehringer Ingelheim drugs are experiencing a shortage: Actilyse and Metalyse. The drugs are used as emergency treatments for adults experiencing acute myocardial infarction, or a heart attack, by dissolving blood clots that have formed in the blood vessels.

The End­points 11: The top pri­vate biotechs in pur­suit of new drugs. Push­ing the en­ve­lope with pow­er­ful new tech­nolo­gies

Right around the beginning of the year, we got a close-up look at what happens after a boom ripples through biotech. The crash of life sciences stocks in Q1 was heard around the world.

In the months since, we’ve seen the natural Darwinian down cycle take effect. Reverse mergers made a comeback, with more burned out shells to go public at a time IPOs and road shows are out of favor. And no doubt some of the more recent arrivals on the investing side of the business are finding greener pastures.

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FDA's out­side ex­perts vote in fa­vor of Fer­ring's fe­cal trans­plant for C. dif­fi­cile, set­ting the stage for Seres

FDA’s outside advisors voted in favor of Ferring Pharmaceuticals’ RBX2660, an experimental poop-based drug implant that the company says would be the first microbiota-based live biotherapeutic to receive an FDA green light.

That was a point repeatedly discussed during the Vaccines and Related Biological Products Advisory Committee, or VRBPAC, meeting Thursday when evaluating Ferring’s fecal microbiota transplant, or FMT, for reducing the recurrence of Clostridioides difficile infection in adults who have received antibiotics. Multiple members brought up the need for a regulated product amid a landscape of unregulated FMTs already happening in clinical care.

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Richard Pazdur, FDA's OCE director (Flatiron Health via YouTube)

FDA's OCE makes the case for ac­cel­er­at­ed ap­proval rid­er in user fee reau­tho­riza­tion

Four experts from the FDA’s Oncology Center of Excellence took to the New England Journal of Medicine yesterday to make the case for not only improving the agency’s ability to expeditiously pull dangling accelerated approvals when, on the rare occasion, confirmatory trials fail, but also better building “quality and efficiency into the AA on-ramp.”

The timely perspective arrives as Congress has exactly one week left to draft, release and sign off on the reauthorized user fee deals before layoff notices will be sent to drug reviewers. That package, which is likely to hitch a ride with the continuing resolution, may or may not include several policy riders (opposed by Republicans), including one that would allow the FDA to require confirmatory trials to be underway before an AA is granted, and would improve the process by which FDA can withdraw AAs.

An­oth­er Cipla site lands a Form 483 over clean­ing is­sues and QC con­trols

A Cipla drug manufacturing site in India has once again landed in the crosshairs of FDA inspectors.

The facility in question is Cipla’s drug manufacturing facility in the village of Verna, in the state of Goa in India’s southwest. In a sign that foreign inspections might ramp up again, the FDA’s visit from Aug. 16 to Aug. 22 uncovered six observations.

The 11-page report noted that environmental monitoring at the site did not properly ensure that microbial contaminants were not making any impact in the aseptic filling areas. It also found that procedures meant to stop microbial contamination were not adequately conducted in aseptic areas of the facility.

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FDA ad­comm takes down Se­cu­ra Bio's leukemia drug af­ter fi­nal tri­al re­sults show po­ten­tial OS detri­ment

The FDA’s Oncologic Drugs Advisory Committee on Friday voted 8-4 against the benefit-risk profile of Secura Bio’s PI3K inhibitor Copiktra (duvelisib), which won approval in September 2018 as a third-line treatment for relapsed or refractory CLL or SLL, but updated pivotal trial results raised safety questions.

In addition to the serious and fatal toxicities of duvelisib, FDA speakers at the ODAC meeting pointed to an evolved treatment landscape for CLL and SLL, with targeted BTK or BCL2 inhibitors (front-line or second-line), and data pointing to a “potential detriment” in overall survival for duvelisib. But some ODAC members noted that the detriment was likely small and that there is some efficacy even as the data are difficult to interpret.

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Solicitor General Elizabeth Prelogar

Should SCO­TUS hear Am­gen's Repatha case? So­lic­i­tor gen­er­al says no

Back in April, Amgen said it was encouraged by the solicitor general’s anticipated review of its Supreme Court petition to rehear a Repatha patent case. They’re likely much less optimistic about the outcome now.

Solicitor General Elizabeth Prelogar wrote in a recent 27-page brief that Amgen’s arguments “lack merit and further review is not warranted.”

The case traces back to a suit filed in 2014 against Sanofi and Regeneron’s Praluent, which ended up beating Amgen’s PCSK9 blockbuster Repatha to market by a month just a year later.