Tesaro makes its case for a clean sweep with ni­ra­parib - and shares soar again

Lon­nie Moul­der

We al­ready knew go­ing in­to the big ES­MO meet­ing that Tesaro’s PARP in­hibitor ni­ra­parib had demon­strat­ed stel­lar re­sults for a range of ovar­i­an can­cer pa­tients with BR­CA mu­ta­tions. But when in­ves­ti­ga­tors stood up to dis­play the re­sults of their piv­otal study, a full set of da­ta demon­strat­ed a ben­e­fit not on­ly for tu­mors that were pos­i­tive for HRD, an im­por­tant bio­mark­er, but al­so for HRD-neg­a­tive tu­mors.

The ben­e­fit nar­rows pro­gres­sive­ly by that last step, but even at a 3.1-month pro­gres­sion sur­vival ben­e­fit for the HRD-neg­a­tive group in the Phase III — 6.9 months ver­sus 3.8 months — in­ves­ti­ga­tors laid the ground­work for ad­vanc­ing this drug for use with­out a di­ag­nos­tic test de­vel­oped by Myr­i­ad Ge­net­ics.

“Even in the HRD-neg­a­tive com­mu­ni­ty, there’s a sub­stan­tial ben­e­fit,” CEO Lon­nie Moul­der told me in the lead­up to the ES­MO con­fer­ence. And he’s pre­pared to make the case for ni­ra­parib with a full set of “ran­dom­ized, con­trolled da­ta we think is quite pow­er­ful.”

“Our con­clu­sion is that all pa­tients have a ben­e­fit and all pa­tients must be treat­ed,” chief in­ves­ti­ga­tor Man­soor Raza Mirza said at the Copen­hagen meet­ing, ac­cord­ing to Reuters’ re­port.

Their study in the New Eng­land Jour­nal of Med­i­cine adds that one in 5 of those HRD-neg­a­tive pa­tients demon­strat­ed a ben­e­fit of greater than 18 months of pro­gres­sion-free sur­vival, a point Tesaro will be mak­ing with reg­u­la­tors. The over­all sur­vival (OS) re­sults have yet to be de­ter­mined, leav­ing reg­u­la­tors to make their de­ci­sions based on PFS re­sults.

Tesaro’s bull­ish po­si­tion was cheered on by in­vestors Mon­day morn­ing, dri­ving up the biotech’s shares by 21% on the added per­spec­tive. And some an­a­lysts, like Leerink’s Sea­mus Fer­nan­dez, helped fu­el the ral­ly with com­ments like this:

Avastin was ap­proved in com­bi­na­tion with chemother­a­py in plat­inum-re­sis­tant ovar­i­an can­cer based on 3.4 month ben­e­fit (6.8 vs. 3.4 months for chemo alone; HR=0.38; p<0.0001). While there are sev­er­al caveats to this com­par­i­son (Avastin was used in com­bi­na­tion in a treat­ment set­ting for plat­inum-re­sis­tant pa­tients and pro­duced a low­er haz­ard ra­tio with a larg­er n), we be­lieve this demon­strates that the FDA can view a 3+ month im­prove­ment in mPFS as clin­i­cal­ly mean­ing­ful.

Johnathan Lan­cast­er, Myr­i­ad’s chief med­ical of­fi­cer, dis­agreed with Tesaro’s as­sess­ment, telling Bloomberg that the HRD-neg­a­tive PFS rate is not clin­i­cal­ly sig­nif­i­cant. He backed that up by not­ing that As­traZeneca’s Lyn­parza, which man­aged to get ap­proved even af­ter a pan­el vot­ed the drug down on weak ear­ly re­sults, was not OK’d for use in BR­CA neg­a­tive pa­tients with a PFS of 3.6 months.

Myr­i­ad Ge­net­ics had this to add in a state­ment to End­points News:

The NO­VA study demon­strat­ed the ef­fi­ca­cy of both the drug and Bio­mark­er. De­spite the su­per sen­si­tive plat­inum re­spon­ders se­lect­ed for the study, my­Choice HRD was able to strat­i­fy based on ben­e­fit. The FDA will need to de­cide whether the 3.1 month ben­e­fit in HRD neg­a­tive pa­tients is suf­fi­cient. This is par­tic­u­lar­ly im­por­tant in the con­text of drugs that have tox­i­c­i­ty in the main­te­nance set­ting where the al­ter­na­tive is no ther­a­py at all.

For pa­tients with non-germline BR­CA mu­ta­tions that were HRD pos­i­tive, the PFS ben­e­fit was much more dis­tinct, a me­di­an 12.9 months ver­sus 3.8 months. The drug was test­ed as a main­te­nance ther­a­py in plat­inum-sen­si­tive, re­cur­rent ovar­i­an can­cer. You can see the full set of da­ta and the dis­cus­sion in the New Eng­land Jour­nal of Med­i­cine.

Re­gard­less of the out­come of the de­bate over HRD sta­tus, Tesaro is lin­ing up for a near term ap­proval that should leave them in a strong mar­ket po­si­tion rel­a­tive to Lyn­parza or Clo­vis On­col­o­gy, which saw its stock price take a hit yes­ter­day over da­ta drawn from a dif­fer­ent set of ovar­i­an can­cer pa­tients. The com­pa­ny has been in­sist­ing that you can’t com­pare stud­ies, but it’s done every day. And as Clo­vis’s stock dropped 18% over the course of Fri­day, it wasn’t far­ing very well.

Pfiz­er, mean­while, plans to ad­vance their ri­val PARP drug ta­la­zoparib, new­ly ac­quired in its $14 bil­lion Medi­va­tion ac­qui­si­tion.

Ryan Watts, Denali CEO

Bio­gen hands De­nali $1B-plus in cash, $1B-plus in mile­stones to part­ner on late-stage Parkin­son’s drug

Biogen is handing over more than a billion dollars cash to partner with the up-and-coming neurosciences crew at Denali on a new therapy for Parkinson’s. And the big biotech is ready to pile on more than a billion dollars more in milestones — if the alliance is a success.

For Biogen $BIIB, the move on Denali’s small molecule inhibitors of LRRK2 puts them in line to collaborate on a late-stage program for DNL151, which is scheduled to start next year.

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Douglas Fambrough, Dicerna CEO (Boehringer Ingelheim via YouTube)

Roche-backed Dicer­na push­es in­to the pack rac­ing to­ward the block­buster hep B goal line, armed with PhI da­ta

Dicerna has lined up a set of proof-of-concept data from a small cohort of hepatitis B patients in a match-up against some heavyweight rivals which got out in front of this race. And right in the front row you’ll find a team from Roche, which paid $200 million in cash and offered another $1.5 billion in milestones to partner with Dicerna $DRNA on their RNAi program for hep B.

Right now it’s looking competitive, with lots of big challenges ahead.

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Jan Hatzius (Photographer: Christopher Goodney/Bloomberg via Getty Images)

When will it end? Gold­man econ­o­mist gives late-stage vac­cines a good shot at tar­get­ing 'large shares' of the US by mid-2021 — but the down­side is daunt­ing

It took decades for hepatitis B research to deliver a slate of late-stage candidates capable of reining the disease in.

With Covid-19, the same timeline has devoured all of 5 months. And the outcome will influence the lives of billions of people and a multitrillion-dollar world economy.

Count the economists at Goldman Sachs as optimistic that at least one of these leading vaccines will stay on this furiously accelerated pace and get over the regulatory goal line before the end of this year, with a shot at several more near-term OKs. That in turn should lead to the production of billions of doses of vaccines that can create herd immunity in the US by the middle of next year, with Europe following a few months later.

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J&J gets a fresh OK for es­ke­t­a­mine, but is it re­al­ly the game-chang­er for de­pres­sion Trump keeps tweet­ing about?

Backed by an enthusiastic set of tweets from President Trump and a landmark OK for depression, J&J scooped up a new approval from the FDA for Spravato today. But this latest advance will likely bring fresh scrutiny to a drug that’s spurred some serious questions about the data, as well as the price.

First, the approval.

Regulators stamped their OK on the use of Spravato — developed as esketamine, a nasal spray version of the party drug Special K or ketamine — for patients suffering from major depressive disorder with acute suicidal ideation or behavior.

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Ab­b­Vie aban­dons a pi­o­neer­ing CRISPR R&D al­liance with Ed­i­tas as Brent Saun­der­s' deal is cast out

A little more than 3 years ago Allergan paid $90 million in a cash upfront to partner with gene editing player Editas on a CRISPR alliance focused on the eye. The lead program centered on LCA10, a rare, inherited retinal degenerative disease that appears in childhood and leads to blindness.

Allergan then went to AbbVie $ABBV in a buyout, and the pharma giant has no interest in moving forward on the gene editing front. The company punted it all back to Editas Thursday, with the biotech $EDIT noting in a statement after the market closed Thursday that it is regaining all rights for its ocular medicines, including EDIT-101.

President Trump speaks with members of the media before boarding Marine One (AP Images)

'Oc­to­ber is com­ing,' and every­one still wants to know if a Covid-19 vac­cine will be whisked through the FDA ahead of the elec­tion

Right on the heels of a lengthy assurance from FDA commissioner Stephen Hahn that the agency will not rush through a quick approval for a Covid-19 vaccine, the President of the United States has some thoughts on timing he’d like to share.

In an exchange with Fox News’ Geraldo Rivera on Thursday, President Trump allowed that a vaccine could be ready to roll “sooner than the end of the year, could be much sooner.”

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Lund­beck sounds taps on an­oth­er CNS drug, re­treat­ing from a mine field still oc­cu­pied by a Mer­ck team

Lundbeck has snipped another clinical-stage branch of its CNS research, dumping a schizophrenia program after determining that their therapy would have no positive influence on the disease.

Designed originally as a 240-patient study, researchers set out in early 2019 to see if a homegrown drug dubbed Lu AF11167 could make it through a proof-of-concept study. The drug is a PDE10Ai inhibitor, targeting an enzyme which it said at the time offered a new pathway to retuning the body’s neurotransmitter dopamine. The big idea was that by hitting their target, the drug would modulate “dopamine D1 and D2 receptor-mediated intraneuronal signaling without binding to these receptors,” influencing negative symptoms of schizophrenia.

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Le­vo Ther­a­peu­tics miss­es pri­ma­ry end­point in PhI­II tri­al of Prad­er-Willi drug — the lat­est set­back in a dis­as­ter-prone field

Marking yet another setback in the Prader-Willi Syndrome field, Levo Therapeutics failed to hit its primary endpoint in a Phase III study of intranasal carbetocin. But the biotech is now shifting its focus to the secondary endpoints in an effort to pluck victory out of the jaws of defeat.

The disorder, characterized by a false sense of starvation, is caused by the absence or deletion of a father’s chromosome 15. Illinois-based Levo’s potential therapy involves a selective oxytocin-receptor agonist.

Leonard Schleifer (AP Images)

Re­gen­eron adds more pos­i­tive PhI­II da­ta for its NGF pro­gram — but safe­ty is still a big con­cern

Two years after fasinumab hit its first late-stage bar, Regeneron is standing by its “high-risk, high reward” bet on the NGF antibody. But while new Phase III data solidified the potential reward, the risk is still threatening to blow it all up.

Regeneron execs and analysts alike now have their eyes set on a rival drug from Pfizer and Eli Lilly, whose fate at the FDA will likely set the scene for the class.