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.

John Hood [file photo]

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On June 18, 2019, we initiated a confidential arbitration proceeding against Dr. Asa Abeliovich, our former consulting co-founder, related to alleged breaches of his consulting agreement and the improper use of our confidential information that he learned during the course of rendering services to us as our consulting Chief Scientific Officer/Chief Innovation Officer. We are in the early stage of this arbitration proceeding and are unable to assess or provide any assurances regarding its possible outcome.

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