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.

Health­care Dis­par­i­ties and Sick­le Cell Dis­ease

In the complicated U.S. healthcare system, navigating a serious illness such as cancer or heart disease can be remarkably challenging for patients and caregivers. When that illness is classified as a rare disease, those challenges can become even more acute. And when that rare disease occurs in a population that experiences health disparities, such as people with sickle cell disease (SCD) who are primarily Black and Latino, challenges can become almost insurmountable.

David Meek, new Mirati CEO (Marlene Awaad/Bloomberg via Getty Images)

Fresh off Fer­Gene's melt­down, David Meek takes over at Mi­rati with lead KRAS drug rac­ing to an ap­proval

In the insular world of biotech, a spectacular failure can sometimes stay on any executive’s record for a long time. But for David Meek, the man at the helm of FerGene’s recent implosion, two questionable exits made way for what could be an excellent rebound.

Meek, most recently FerGene’s CEO and a past head at Ipsen, has become CEO at Mirati Therapeutics, taking the reins from founding CEO Charles Baum, who will step over into the role of president and head of R&D, according to a release.

Who are the women su­per­charg­ing bio­phar­ma R&D? Nom­i­nate them for this year's spe­cial re­port

The biotech industry has faced repeated calls to diversify its workforce — and in the last year, those calls got a lot louder. Though women account for just under half of all biotech employees around the world, they occupy very few places in C-suites, and even fewer make it to the helm.

Some companies are listening, according to a recent BIO survey which showed that this year’s companies were 2.5 times more likely to have a diversity and inclusion program compared to last year’s sample. But we still have a long way to go. Women represent just 31% of biotech executives, BIO reported. And those numbers are even more stark for women of color.

Jacob Van Naarden (Eli Lilly)

Ex­clu­sives: Eli Lil­ly out to crash the megablock­buster PD-(L)1 par­ty with 'dis­rup­tive' pric­ing; re­veals can­cer biotech buy­out

It’s taken 7 years, but Eli Lilly is promising to finally start hammering the small and affluent PD-(L)1 club with a “disruptive” pricing strategy for their checkpoint therapy allied with China’s Innovent.

Lilly in-licensed global rights to sintilimab a year ago, building on the China alliance they have with Innovent. That cost the pharma giant $200 million in cash upfront, which they plan to capitalize on now with a long-awaited plan to bust up the high-price market in lung cancer and other cancers that have created a market worth tens of billions of dollars.

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When ef­fi­ca­cy is bor­der­line: FDA needs to get more con­sis­tent on close-call drug ap­provals, agency-fund­ed re­search finds

In the exceedingly rare instances in which clinical efficacy is the only barrier to a new drug’s approval, new FDA-funded research from FDA and Stanford found that the agency does not have a consistent standard for defining “substantial evidence” when flexible criteria are used for an approval.

The research comes as the FDA is at a crossroads with its expedited-review pathways. The accelerated approval pathway is under fire as the agency recently signed off on a controversial new Alzheimer’s drug, with little precedent to explain its decision. Meanwhile, top officials like Rick Pazdur have called for a major push to simplify and clarify all of the various expedited pathways, which have grown to be must-haves for sponsors of nearly every newly approved drug.

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Ted White, Verrica CEO

Ver­ri­ca hits an­oth­er bump in the road with CMO re­lat­ed let­ter from FDA

The FDA has rejected Verrica’s new drug application for VP-102 again, with the company pinning the CRL on problems at a CMO that it was partnered with, the company announced Monday.

The FDA didn’t raise issues that directly relate to the manufacturing of VP-102, the company said, but raised “general quality issues” at the CMO’s facility. There were also no clinical concerns, it said, or need to collect more data.

Take­da snaps up the Japan­ese rights to an old Shire cast-off; Boehringer In­gel­heim ac­quires Abexxa Bi­o­log­ics

A week before the FDA is set to decide on Mirum Pharmaceuticals’ lead liver disease drug — an old Shire cast-off called maralixibat — Takeda is swooping in to secure the rights in Japan.

Maralixibat’s roots trace back to Lumena, which was snapped up by Shire for $260 million-plus back in 2014. While the candidate had failed mid-stage studies at Shire, Mirum believes better trial design and patient selection will deliver the wins it needs. The drug is currently in development for Alagille syndrome (a condition called ALGS in which bile builds up in the liver), progressive familial intrahepatic cholestasis (PFIC, which causes progressive liver disease) and biliary atresia (a blockage in the ducts that carry bile from the liver to the gallbladder).

Volker Wagner (L) and Jeff Legos

As Bay­er, No­var­tis stack up their ra­dio­phar­ma­ceu­ti­cal da­ta at #ES­MO21, a key de­bate takes shape

Ten years ago, a small Norwegian biotech by the name of Algeta showed up at ESMO — then the European Multidisciplinary Cancer Conference 2011 — and declared that its Bayer-partnered targeted radionuclide therapy, radium-223 chloride, boosted the overall survival of castration-resistant prostate cancer patients with symptomatic bone metastases.

In a Phase III study dubbed ALSYMPCA, patients who were treated with radium-223 chloride lived a median of 14 months compared to 11.2 months. The FDA would stamp an approval on it based on those data two years later, after Bayer snapped up Algeta and christened the drug Xofigo.

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Mi­rati tri­umphs again in KRAS-mu­tat­ed lung can­cer with a close­ly watched FDA fil­ing now in the cards

After a busy weekend at #ESMO21, which included a big readout for its KRAS drug adagrasib in colon cancer, Mirati Therapeutics is ready to keep the pressure on competitor Amgen with lung cancer data that will undergird an upcoming filing.

In topline results from a Phase II cohort of its KRYSTAL-1 study, adagrasib posted a response rate of 43% in second-line-or-later patients with metastatic non-small cell lung cancer containing a KRAS-G12C mutation, Mirati said Monday.