#ES­MO20: As­traZeneca aims to spur PRO­found shift in prostate can­cer treat­ment with Lyn­parza OS da­ta

As­traZeneca has un­veiled the fi­nal, ma­ture over­all sur­vival da­ta that ce­ment­ed Lyn­parza’s first ap­proval in prostate can­cer ap­proval — tout­ing its lead against ri­vals with the on­ly PARP in­hibitor to have demon­strat­ed such ben­e­fit.

But get­ting the Mer­ck-part­nered drug to the right pa­tients re­mains a chal­lenge, some­thing the com­pa­nies are hop­ing to change with the new da­ta cut.

José Basel­ga

The OS num­bers on the sub­group with BR­CA1/2 or ATM-mu­tat­ed metasta­t­ic cas­tra­tion-re­sis­tant prostate can­cer are sim­i­lar to the first look on of­fer when the FDA ex­pand­ed the la­bel in May: Lyn­parza re­duced the risk of death by 31% ver­sus Xtan­di and Zyti­ga. Pa­tients on Lyn­parza lived a me­di­an of 19.1 months, com­pared to 14.7 months for the an­ti-an­dro­gen ther­a­pies (p = 0.0175).

As PRO­found fo­cused on the sec­ond-line set­ting, the pa­tients in the tri­al had all pro­gressed on pri­or treat­ment. In­ves­ti­ga­tors showed up in Barcelona last year to de­tail the pro­gres­sion-free sur­vival win; over­all sur­vival was the sec­ondary end­point.

While the re­sults are more or less ex­pect­ed, José Basel­ga, As­traZeneca’s chief of can­cer R&D, high­light­ed the fact that 66% of the pa­tients on the con­trol arm had crossed over to Lyn­parza.

“So if de­spite 67% crossover, which is a very high num­ber, you see an im­prove­ment in sur­vival, the ques­tion that we’re an­swer­ing is no longer a ques­tion on whether ola­parib im­proves sur­vival or not — the an­swer is yes — but the ques­tion that we’re an­swer­ing in an in­di­rect fash­ion is do we need to start ola­parib ear­li­er or not,” he said. “And I think that that’s what this is telling. So I think that this be­comes a very clear in­di­ca­tion that we need to start ola­parib ear­ly in the in­tend­ed use as op­posed to wait.”

No­tably, Lyn­parza wasn’t just ap­proved to treat pa­tients with BR­CA1/2 and ATM mu­ta­tions; there are 12 oth­er ho­mol­o­gous re­com­bi­na­tion re­pair (HRR) gene mu­ta­tions on the la­bel. On that broad­er tri­al pop­u­la­tion, an ex­plorato­ry analy­sis found a non-sta­tis­ti­cal­ly sig­nif­i­cant im­prove­ment in OS, with a haz­ard ra­tio of 0.79. Me­di­an OS was 17.3 months, 3.3 months longer than the Xtan­di/Zyti­ga arm.

Dave Fredrick­son

It re­mains to be seen whether that would con­vince more physi­cians to adopt that 15-gene as­say, the com­pan­ion di­ag­nos­tic for Lyn­parza in the mCR­PC set­ting that As­traZeneca es­ti­mates would find about one in four pa­tients el­i­gi­ble. The drug is, af­ter­all, the first tar­get­ed ther­a­py ap­proved for this space.

Dave Fredrick­son, who leads As­traZeneca’s on­col­o­gy busi­ness unit, con­ced­ed that test­ing for HRR gene mu­ta­tions be­yond BR­CA is “not yet suf­fi­cient­ly wide­spread.”

“In PRO­found, the over­all sur­vival ben­e­fit cre­ates an im­por­tant im­pe­tus for health­care prac­ti­tion­ers around the globe to em­brace test­ing; they want to en­sure each pa­tient is matched with the tar­get­ed med­i­cine from which he will most ben­e­fit,” he wrote to End­points News.

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.

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.

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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Adrian Gottschalk, Foghorn CEO (Foghorn)

Foghorn hits Nas­daq in $120M de­but as the biotech IPO boom shows no sign of slow­ing

It’s been a record year for biotech IPOs, and the execs at Nasdaq would like nothing better than to see that momentum continue into the first half of next year.

Since January, 72 biotech and biopharma companies have hit Wall Street, according to Nasdaq head of healthcare listings Jordan Saxe, together raising $13.2 billion.

The latest is Flagship’s Foghorn Therapeutics, which priced its shares last night at $16 apiece, the midpoint of a $15 to $17 range. The Cambridge, MA-based biotech — which initially filed for a $100 million raise on Oct. 2 — is netting $120 million from a 7.5 million-share offering. The proceeds will go right into its gene traffic control platform, including two lead preclinical oncology candidates.