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.

De­vel­op­ment of the Next Gen­er­a­tion NKG2D CAR T-cell Man­u­fac­tur­ing Process

Celyad’s view on developing and delivering a CAR T-cell therapy with multi-tumor specificity combined with cell manufacturing success
Overview
Transitioning potential therapeutic assets from academia into the commercial environment is an exercise that is largely underappreciated by stakeholders, except for drug developers themselves. The promise of preclinical or early clinical results drives enthusiasm, but the pragmatic delivery of a therapy outside of small, local testing is most often a major challenge for drug developers especially, including among other things, the manufacturing challenges that surround the production of just-in-time and personalized autologous cell therapy products.

Paul Hudson, Getty Images

UP­DAT­ED: Sanofi CEO Hud­son lays out new R&D fo­cus — chop­ping di­a­betes, car­dio and slash­ing $2B-plus costs in sur­gi­cal dis­sec­tion

Earlier on Monday, new Sanofi CEO Paul Hudson baited the hook on his upcoming strategy presentation Tuesday with a tell-tale deal to buy Synthorx for $2.5 billion. That fits squarely with hints that he’s pointing the company to a bigger future in oncology, which also squares with a major industry tilt.

In a big reveal later in the day, though, Hudson offered a slate of stunners on his plans to surgically dissect and reassemble the portfoloio, saying that the company is dropping cardio and diabetes research — which covers two of its biggest franchise arenas. Sanofi missed the boat on developing new diabetes drugs, and now it’s pulling out entirely. As part of the pullback, it’s dropping efpeglenatide, their once-weekly GLP-1 injection for diabetes.

“To be out of cardiovascular and diabetes is not easy for a company like ours with an incredibly proud history,” Hudson said on a call with reporters, according to the Wall Street Journal. “As tough a choice as that is, we’re making that choice.”

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Re­pub­li­cans un­veil a drug price bill to ri­val the De­moc­rats — promis­ing low­er prices and more cures

Nancy Pelosi unveiled the Democrats’  drug pricing bill back in September and brought the fight straight to the industry with a proposal to empower the US government to negotiate prices for select drugs. Republicans, who decried the bill reeks of heavy-handed government intervention which will stifle innovation, now have a counterproposal they claim will result in cheaper drugs and incentivize R&D — further clouding the prospects of a bipartisan compromise that could land on Donald Trump’s desk.

Chris Garabedian. Xontogeny

Per­cep­tive teams up with Chris Garabe­di­an to open up a new, $210M biotech fund fo­cused on A rounds

Perceptive Advisors is one of those prolific biotech investor groups which has traditionally enjoyed zeroing in on clinical-stage investments and crossover rounds, a group that prefers more established drug development players with near-term payoff potential.

But now they’re partnering with Xontogeny chief and longtime biotech entrepreneur Chris Garabedian on a $210 million fund — with money contributed by institutional investors and family funds — to go into the launch space with their first early-stage VC fund. Dubbed the Perceptive Xontogeny Venture Fund, LP, or just PXV Fund, they plan to favor upstarts that Garabedian is fostering in his incubator. But they’ll also plan to reach outside that inner circle for more A rounds to back, with plans to dominate initial funding with $10 million to $20 million per newborn biotech.

Roger Perlmutter, Merck

#ASH19: Here’s why Mer­ck is pay­ing $2.7B to­day to grab Ar­Qule and its next-gen BTK drug, lin­ing up Eli Lil­ly ri­val­ry

Just a few months after making a splash at the European Hematology Association scientific confab with an early snapshot of positive data for their BTK inhibitor ARQ 531, ArQule has won a $2.7 billion buyout deal from Merck.

Merck is scooping up a next-gen BTK drug — which is making a splash at ASH today — from ArQule in an M&A pact set at $20 a share $ARQL. That’s more than twice Friday’s $9.66 close. And Merck R&D chief Roger Perlmutter heralded a deal that nets “multiple clinical-stage oral kinase inhibitors.”

This is the second biotech buyout pact today, marking a brisk tempo of M&A deals in the lead-up to the big JP Morgan gathering in mid-January. It’s no surprise the acquisitions are both for cancer drugs, where Sanofi will try to make its mark while Merck beefs up a stellar oncology franchise. And bolt-ons are all the rage at the major pharma players, which you could also see in Novartis’ recent $9.7 billion MedCo buyout.

ArQule — which comes out on top after their original lead drug foundered in Phase III — highlighted early data on ‘531 at EHA from a group of 6 chronic lymphocytic leukemia patients who got the 65 mg dose. Four of them experienced a partial response — a big advance for a company that failed with earlier attempts.

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Left top to right: Mark Timney, Alex Denner, Vas Narasimhan. (The Medicines Company, Getty, AP/Endpoints News)

In a play-by-play of the $9.7B Med­Co buy­out, No­var­tis ad­mits it over­paid while of­fer­ing a huge wind­fall to ex­ecs

A month into his tenure at The Medicines Company, new CEO Mark Timney reached out to then-Novartis pharma chief Paul Hudson: Any interest in a partnership?

No, Hudson told him. Not now, at least.

Ten months later, Hudson had left to run Sanofi and Novartis CEO Vas Narasimhan was paying $9.7 billion for the one-drug biotech – the largest in the string of acquisitions Narasimhan has signed since his 2017 appointment.

The deal was the product of an activist investor and his controversial partner working through nearly a year of cat-and-mouse negotiations to secure a deal with Big Pharma’s most expansionist executive. It represented a huge bet in a cardiovascular field that already saw two major busts in recent years and brought massive returns for two of the industry’s most eye-raising names.

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US biosim­i­lar launch­es about to turn a cor­ner

The US biosimilar industry has lingered in the shadow of the European market since the US pathway for approvals was initiated in 2009.

Ten years later (or less than five years since the first FDA approval of a biosimilar), and just 42% (11 out of 26) of FDA-approved biosimilars have launched. But in the next three months (see chart below), a clutch of new biosimilars will hit the market, including new ones in oncology, hinting at a wave of uptake.

Paul Hudson. Sanofi

New Sanofi CEO Hud­son adds next-gen can­cer drug tech to the R&D quest, buy­ing Syn­thorx for $2.5B

When Paul Hudson lays out his R&D vision for Sanofi tomorrow, he will have a new slate of interleukin therapies and a synthetic biology platform to boast about.

The French pharma giant announced early Monday that it is snagging San Diego biotech Synthorx in a $2.5 billion deal. That marks an affordable bolt-on for Sanofi but a considerable return for Synthorx backers, including Avalon, RA Capital and OrbiMed: At $68 per share, the price represents a 172% premium to Friday’s closing.

Synthorx’s take on alternative IL-2 drugs for both cancer and autoimmune disorders — enabled by a synthetic DNA base pair pioneered by Scripps professor Floyd Romesberg — “fits perfectly” with the kind of innovation that he wants at Sanofi, Hudson said.

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Game on: Re­gen­eron's BC­MA bis­pe­cif­ic makes clin­i­cal da­ta de­but, kick­ing off mul­ti­ple myelo­ma matchup with Bris­tol-My­ers

As J&J attempts to jostle past Bristol-Myers Squibb and bluebird for a landmark approval of its anti-BCMA CAR-T — and while GlaxoSmithKline maps a quick path to the FDA riding on its own BCMA-targeting antibody-drug conjugates — the bispecifics are arriving on the scene to stake a claim for a market that could cross $10 billion per year.

The main rivalry in multiple myeloma is shaping up to be one between Regeneron and Bristol-Myers, which picked up a bispecific antibody to BCMA through its recently closed $74 billion takeover of Celgene. Both presented promising first-in-human data at the ASH 2019 meeting.