As­traZeneca throws down the gaunt­let with a PhI­II vic­to­ry in head-to-head PARP war with Tesaro

Sean Bo­hen, As­traZeneca

As­traZeneca has post­ed an­oth­er suc­cess in its cam­paign to ex­pand the use of its PARP in­hibitor Lyn­parza (ola­parib).

In what has be­come a head-to-head show­down with Tesaro, which has a ri­val PARP un­der re­view at the FDA, As­traZeneca to­day her­ald­ed a top-line suc­cess for Lyn­parza in a Phase III study of HER2-neg­a­tive metasta­t­ic breast can­cer har­bor­ing germline BR­CA1 or BR­CA2 mu­ta­tions.

Like Tesaro, As­traZeneca’s piv­otal study fo­cused on a com­par­i­son with physi­cian’s choice of chemother­a­pies, with Lyn­parza com­ing out ahead on pro­gres­sion-free sur­vival.

Lyn­parza got an ear­ly start in the mar­ket, thanks to FDA re­view­ers who were will­ing to look past the rel­a­tive­ly weak da­ta that As­traZeneca $AZN had post­ed for this drug. Richard Paz­dur’s team was anx­ious to get a PARP in­to the mar­ket for ovar­i­an can­cer, where Tesaro is lin­ing up its first shot on their fran­chise drug. A few back­ers on the sell side have pro­ject­ed bil­lions in peak sales for Tesaro’s drug, but they’ll have to get around As­traZeneca to get it.

As we re­port­ed a few days ago, ni­ra­parib sits high on a list of 15 po­ten­tial block­busters ready to hit the mar­ket this year, with 2022 sales rev­enue pro­ject­ed at $1.8 bil­lion for the ovar­i­an can­cer mar­ket. And that has kept the fo­cus on on­go­ing buzz about a po­ten­tial buy­out for Tesaro.

An­a­lysts will have to wait for the ac­tu­al da­ta, though, on an in­di­ca­tion that they say could be worth a block­buster bil­lion dol­lars in an­nu­al rev­enue for Tesaro. Sea­mus Fer­nan­dez called it a clear win for the phar­ma gi­ant:

This is the first Phase 3 read­out for a PARP in­hibitor in breast can­cer and will like­ly have pos­i­tive read-through for sim­i­lar­ly de­signed tri­als of PFE’s (MP) ta­la­zoparib (EM­BRA­CA tri­al; da­ta ex­pect­ed in 1H:17) and TSRO’s (MP) ni­ra­parib (BRA­VO tri­al; da­ta ex­pect­ed in 2H:17). Im­por­tant­ly, this rep­re­sents a win for AZN, which is build­ing its DNA Dam­age Re­sponse (DDR) port­fo­lio around Lyn­parza, as well as pro­vid­ing the first val­i­da­tion for the PARP in­hibitor class out­side of ovar­i­an can­cer. We con­tin­ue to view AZN as our top pick with a num­ber of high-im­pact cat­a­lysts on the hori­zon. Re­it­er­ate OP.

Shares of As­traZeneca jumped 1.7% on the news.

The suc­cess is a key win for As­traZeneca, which has been work­ing hard to fol­low up on Lyn­parza’s ap­proval with sol­id ev­i­dence of its broad­er po­ten­tial. The drug has proven to be one of the few big bright spots for the phar­ma gi­ant as it awaits com­bo da­ta on the check­point in­hibitor dur­val­um­ab and treme­li­mum­ab.

These aren’t the on­ly two PARPs in the pipeline. Pfiz­er ac­quired ta­la­zoparib in its $14 bil­lion buy­out of Medi­va­tion while Clo­vis achieved an ap­proval for Rubra­ca last De­cem­ber.

As­traZeneca CMO Sean Bo­hen said:

These re­sults are pos­i­tive news for pa­tients with BR­CA-mu­tat­ed metasta­t­ic breast can­cer, a dis­ease with a high un­met need, and are the first pos­i­tive Phase III da­ta for a PARP in­hibitor be­yond ovar­i­an can­cer. This is high­ly en­cour­ag­ing for the de­vel­op­ment of our broad port­fo­lio which aims to treat mul­ti­ple can­cers by tar­get­ing DNA dam­age re­sponse path­ways.

How Pa­tients with Epilep­sy Ben­e­fit from Re­al-World Da­ta

Amanda Shields, Principal Data Scientist, Scientific Data Steward

Keith Wenzel, Senior Business Operations Director

Andy Wilson, Scientific Lead

Real-world data (RWD) has the potential to transform the drug development industry’s efforts to predict and treat seizures for patients with epilepsy. Anticipating or controlling an impending seizure can significantly increase quality of life for patients with epilepsy. However, because RWD is secondary data originally collected for other purposes, the challenge is selecting, harmonizing, and analyzing the data from multiple sources in a way that helps support patients.

Re­gen­eron's Evkeeza shows promise in curb­ing high triglyc­erides, but will ge­net­ic dis­par­i­ties lim­it use?

When Regeneron scored an early approval for lipid lowering antibody Evkeeza back in February, the drugmaker cracked open a new pathway to lower abnormally high cholesterol levels. Now, Regeneron is chasing high triglycerides as well with some promising mid-stage data — but will genetic restrictions limit the drug’s use?

Regeneron’s Evkeeza (evinacumab) cut median triglyceride levels by more than 800 mg/dL (57%) in patients with a rare disorder causing abnormally high triglyceride levels compared with an overall increase of 50 mg/dL (1.8%) in participants on placebo, according to Phase II data presented Sunday at the virtual American College of Cardiology meeting.

$DNA is once again on NYSE; FDA clears Soliris chal­lenger for the mar­ket; Flag­ship’s think­ing big again with eR­NA; and more

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I still remember the uncertainty in the air last year when nobody was sure whether ASCO would cancel their in-person meeting. But it’s now back again for the second virtual conference, and Endpoints News is here for it. Check out our 2-day event reviewing the landscape of cancer R&D and send news our way.

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As­traZeneca's Farx­i­ga missed big on Covid-19 study, but it's tak­ing SGLT2 safe­ty da­ta as a sil­ver lin­ing

AstraZeneca hasn’t seen many setbacks in recent months for SGLT2 inhibitor Farxiga, which broke ground in heart failure and kidney disease regardless of diabetes diagnosis. But the British drugmaker had to admit defeat in taking Farxiga into Covid-19, but follow-up results add a bit of a silver lining to that trial’s safety data.

Of hospitalized Covid-19 patients dosed with AstraZeneca’s Farxiga, 11.2% experienced an organ failure or died after 30 days of therapy compared with 13.8% of those given placebo, according to follow-up data from the DARE-19 study revealed Sunday at the virtual American College of Cardiology meeting.

Pfiz­er, Bris­tol My­er­s' Eliquis flops in post-heart surgery pa­tients, spurring an 'un­ex­plained sig­nal' in cer­tain deaths

Pfizer and Bristol Myers Squibb’s non-warfarin blood thinner Eliquis has raced out to become the most prescribed drug of its class on the market — even overtaking warfarin’s long-time lead. But in tricky-to-treat patients after a valve replacement, an investigator-sponsored study couldn’t turn up benefit and raised a troubling safety signal.

Eliquis failed to show benefit over standard of care in preventing serious clinical outcomes after a transaortic valve replacement (TAVR) and was linked to an “unexplained signal” in a subset of populations with a higher rate of non-CV deaths who did not need blood thinners apart from the surgery, according to data presented Saturday at the virtual American College of Cardiology meeting.

Gene ther­a­py from Bio­gen's $800M buy­out flops in mid-stage study, deal­ing blow to new am­bi­tions

The #2 candidate from Biogen’s $800 million ocular gene therapy buyout has failed in a mid-stage trial, dealing an early blow to the big biotech’s plans to revitalize its pipeline with new technologies.

Biogen announced that the candidate, an experimental treatment for a rare and progressive form of blindness called X-linked retinitis pigmentosa (XLRP), failed to sufficiently improve vision in patients’ treated eye — patients only received an injection in one eye — after a year, on a standard scale, compared to their untreated eye. The company said they saw “positive trends” on several secondary endpoints, including visual acuity, but declined to say whether the trial actually hit any of those endpoints.

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Michael Dell (Richard Drew, AP Images)

'Dude, you're get­ting a Del­l' — as a new deep-pock­et biotech in­vestor

What happens when you marry longtime insiders in the global biotech VC game with the family fund of tech billionaire Michael Dell, a synthetic biology legend out of MIT and Harvard and the former director of the NCI?

Today, the answer is a newly financed, $200 million biotech SPAC now cruising the industry for a top player interested in finding a short cut to Nasdaq.

Orion Biotech Opportunities priced their blank check company today, raising $200 million with Dell’s multibillion-dollar MSD group’s commitment on investing another $20 million in a forward-purchase agreement.

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Bris­tol My­ers backs up its case for heart drug mava­camten as FDA weighs app in car­diomy­opa­thy

When Bristol Myers Squibb signed off on its $13 billion acquisition of MyoKardia back in October, it was making a big bet that lead drug mavacamten could prove a game changer in cardiac myopathy. Now, with the drug up for FDA review, Bristol Myers is backing up its case with new quality of life data.

Patients dosed with myosin inhibitor mavacamten posted a clinically significant increase in scores on the Kansas City Cardiomyopathy Questionnaire, a catch-all summary of symptoms and quality of life markers, over placebo at 30 weeks, according to data from the Phase III EXPLORER-HCM study presented Saturday at the virtual American College of Cardiology meeting.

Vas Narasimhan (Photographer: Simon Dawson/Bloomberg via Getty Images)

No­var­tis whiffs on En­tresto study af­ter heart at­tacks — but that does­n't mean it's go­ing down qui­et­ly

If Novartis learned one thing from its interaction with the FDA over its latest heart failure approval for Entresto, it was that missing a primary endpoint may not be the nail in the coffin. Now, Entresto has missed again on a late-stage study in high-risk heart patients, and it’s already sowing the seeds for a path forward regardless.

Novartis’ Entresto couldn’t best standard-of-care ramipril in staving off a composite of deaths and heart failure events in patients with left ventricular systolic dysfunction and/or pulmonary congestion who have had a prior heart attack, according to topline data from the Phase III PARADISE-MI study revealed Saturday at the virtual American College of Cardiology meeting.