Re­gen­eron, Sanofi make their case for an­oth­er PD-1 drug — and they’re not set­tling for sixth place

Jo Lager, Sanofi

CHICA­GO — The two top im­muno-on­col­o­gy in­ves­ti­ga­tors for Re­gen­eron $REGN and Sanofi, Is­rael ‘Izzy’ Lowy and Jo Lager, came to Chica­go to of­fer a very promis­ing snap­shot of the ear­ly da­ta they’ve reaped from a study of their PD-1 drug REGN2810 for cu­ta­neous squa­mous cell car­ci­no­ma — the sec­ond dead­liest form of skin can­cer be­hind melanoma.

Like No­var­tis or In­cyte or some of the oth­er com­pa­nies work­ing on PD-(L)1 ther­a­pies in the large sec­ond wave form­ing in the pipeline fol­low­ing the first 5 that have been ap­proved, these two ma­jor league play­ers see this as a key build­ing block for the com­bos they want to de­vel­op. But it would be a mis­take, they say, to sim­ply write this one off as the lat­est check­point of this stripe look­ing to line up for the mar­ket.

Is­rael Lowy, Re­gen­eron

“I don’t think we’re the sixth,” Lowy told me in a con­ver­sa­tion over the week­end. “We’re the third.”

Re­gen­eron has some of the best an­ti­body spe­cial­ists in the busi­ness, which they’ve proved with a string of new drug ap­provals. Lowy says he’s learned a lot about PD-(L)1 while they’ve been work­ing on REGN2810. And some of their in­sights have ma­jor im­pli­ca­tions for every­one work­ing in the field.

One of the biggest lessons is that PD-1 is a sig­nif­i­cant­ly bet­ter path­way to fol­low than PD-L1, says Lowy.

The team cre­at­ed a PD-L1 as a com­ple­men­tary pro­gram in case their work on PD-1, but they feel now that PD-1 ther­a­pies of­fer a much more ef­fec­tive way to  un­leash an im­mune at­tack, some­thing that’s been un­der­scored by the dom­i­nance of Keytru­da and Op­di­vo  as well as Roche’s re­cent stun­ning set­back with the PD-L1 drug Tecen­triq.

And that’s why Re­gen­eron and Sanofi feel they can leapfrog ahead of some of the ear­ly en­tries.

Re­gen­eron and Sanofi al­so didn’t set out to cre­ate a bet­ter PD-1 than Keytru­da or Op­di­vo.

“One of the things was a ma­jor re­quire­ment for it to be at least as good as any­one else’s,” says Lowy, “not as­sum­ing that we could make an an­ti­body that was bet­ter. That be­ing said, we’re very hap­py with it. We screened many an­ti­bod­ies to pick the one that was our bet­ter can­di­date.”

Not on­ly is the first cut of the da­ta very good, this check­point is al­ready in a po­ten­tial­ly piv­otal Phase II tri­al.

Here’s what they found:

REGN2810 de­liv­ered an im­pres­sive over­all re­sponse rate of 46.2% — 12 of 26 pa­tients — which in­cludes 2 com­plete re­spons­es, 9 par­tial re­spons­es and 1 un­con­firmed par­tial re­sponse. The dis­ease con­trol rate hit 69.2%, cov­er­ing 18 of 26 pa­tients with 12 ORR and 6 with sta­ble dis­ease. The me­di­an pro­gres­sion-free sur­vival and over­all sur­vival rate were not reached at the da­ta cut­off date with a me­di­an fol­low-up of 6.9 months. Ten pa­tients re­main in re­sponse as of the da­ta cut­off date, with a range of 8 to 40 weeks du­ra­tion of re­sponse.

Ge­of­frey Porges, Leerink

Leerink’s Ge­of­frey Porges called the re­sults “com­pelling,” not­ing that the Re­gen­eron/Sanofi team could have a $300 mil­lion peak sales op­por­tu­ni­ty in the US alone. “(T)he com­pa­ny will al­most cer­tain­ly file an ap­pli­ca­tion with the two tri­als, and then take the risk of a pos­si­ble ad­vi­so­ry com­mit­tee re­view (new drug/new in­di­ca­tion for PD-1) about the clin­i­cal sig­nif­i­cance of the re­sult and the im­por­tance of the in­di­ca­tion.”

“We rec­og­nized long ago that block­ade of the PD-1 path­way is an es­sen­tial com­po­nent of any im­muno-on­col­o­gy pro­gram,” Lowy tells me. “Al­though a fab­u­lous ad­vance, it’s re­al­ly just the first chap­ter, or a pref­ace.”

“We want to have our own to fa­cil­i­tate the abil­i­ty to de­vel­op nov­el com­bi­na­tions with­out hav­ing to re­ly on any­one else’s agent,” he adds.

Re­gen­eron and Sanofi are well on their way. The rest of the in­dus­try might want to pay more at­ten­tion.

Brian Kaspar. AveXis via Twitter

AveX­is sci­en­tif­ic founder fires back at No­var­tis CEO Vas Narasimhan, 'cat­e­gor­i­cal­ly de­nies any wrong­do­ing'

Brian Kaspar’s head was among the first to roll at Novartis after company execs became aware of the fact that manipulated data had been included in its application for Zolgensma, now the world’s most expensive therapy.

But in his first public response, the scientific founder at AveXis — acquired by Novartis for $8.7 billion — is firing back. And he says that not only was he not involved in any wrongdoing, he’s ready to defend his name as needed.

I reached out to Brian Kaspar after Novartis put out word that he and his brother Allen had been axed in mid-May, two months after the company became aware of the allegations related to manipulated data. His response came back through his attorneys.

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As­traZeneca’s Imfinzi/treme com­bo strikes out — again — in lung can­cer. Is it time for last rites?

AstraZeneca bet big on the future of their PD-L1 Imfinzi combined with the experimental CTLA-4 drug tremelimumab. But once again it’s gone down to defeat in a major Phase III study — while adding damage to the theory involving targeting cancer with a high tumor mutational burden.

Early Wednesday the pharma giant announced that their NEPTUNE study had failed, with the combination unable to beat standard chemo at overall survival in high TMB cases of advanced non-small cell lung cancer. We won’t get hard data until later in the year, but the drumbeat of failures will call into question what — if any — future this combination can have left.

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We­bi­nar: Re­al World End­points — the brave new world com­ing in build­ing fran­chise ther­a­pies

Several biopharma companies have been working on expanding drug labels through the use of real world endpoints, combing through the data to find evidence of a drug’s efficacy for particular indications. But we’ve just begun. Real World Evidence is becoming an important part of every clinical development plan, in the soup-through-nuts approach used in building franchises.

I’ve recruited a panel of 3 top experts in the field — the first in a series of premium webinars — to look at the practical realities governing what can be done today, and where this is headed over the next few years, at the prodding of the FDA.

ZHEN SU — Merck Serono’s Senior Vice President and Global Head of Oncology

ELLIOTT LEVY — Amgen’s Senior Vice President of Global Development

CHRIS BOSHOFF — Pfizer Oncology’s Chief Development Officer

A premium subscription to Endpoints News is required to attend this webinar. Please upgrade to either an Insider or Enterprise plan for access. Already have Endpoints Premium? Please sign-in below. You can contact our Subscriptions team at with any issues.

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UP­DAT­ED: Pay­back? An­a­lysts say Sarep­ta was blind­sided by an FDA re­jec­tion dri­ven by reg­u­la­to­ry re­venge

In one of the least anticipated moves of the year, the FDA has rejected Sarepta’s application for an accelerated approval of its Duchenne MD drug golodirsen after fretting over safety issues.

In a statement that arrived after the bell on Monday, Sarepta explained the CRL, saying:

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Levi Garraway. Broad Institute via Youtube

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Ritu Baral Cowen
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FDA regulators have set a PDUFA date of March 19, 2020, just a year after the Boston biotech posted positive Phase III results showing that people with two F508del mutations experienced statistically significant improvements in lung function after a 4-week regimen of VX-445, tezacaftor and ivacaftor. After reviewing 24-week data among patients with one F508del mutation and one minimal function mutation — and thoroughly comparing the VX-445 triple with another combo featuring VX-659 on scores like safety, drug-drug interactions, and photosensitivity — Vertex ultimately went with VX-445.

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Their Phase Ib/IIa study for SYNB1020 to counter the accumulation of ammonia in the body, a condition called hyperammonemia or urea cycle disorder, floundered at the interim readout, forcing the biotech to kill it and reserve its cash for pipeline therapies with greater potential.

Elan­co to buy Bay­er's an­i­mal health busi­ness for $7.6B, as deal­mak­ing gath­ers steam in the sec­tor

Last week, Elanco explicitly dodged answering questions about its rumored interest in Bayer’s animal health business in its post-earnings call. On Tuesday, the Eli Lilly spinoff disclosed it was purchasing the German drug maker’s veterinary unit in a cash-and-stock deal worth $7.6 billion. 

Elanco $ELAN has been busy on the deal-making front. In April, it laid out plans to swallow its partner, Kansas-based pet therapeutics company Aratana $PETX. A July report by Reuters suggested a potential Bayer deal was being explored, and Bloomberg last week said the deal was imminent, citing sources.