The best of the rest: High­lights from the be­low-the-fold pre­sen­ta­tions at #ES­MO21

This year’s ES­MO Con­gress has had a ma­jor fo­cus on Big Phar­ma drugs — most no­tably can­di­dates from Mer­ck and As­traZeneca — but there have al­so been up­dates from small­er biotechs with da­ta look­ing to chal­lenge the big-name drug­mak­ers.

To­day, we’re high­light­ing some of the da­ta re­leas­es that flew un­der the radar at #ES­MO21 — whether from ear­ly-stage drugs look­ing to make a mark or old­er stal­warts with in­ter­est­ing fol­low-up da­ta.

Here’s the best of the rest:

Agenus high­lights PD-1/CT­LA-4 da­ta in ad­vanced cer­vi­cal can­cer

Agenus on Sun­day pre­sent­ed fi­nal re­sults from its Phase II C-550 study show­ing a com­bi­na­tion of its bal­stil­imab and za­l­ifre­limab post­ed a re­sponse rate of 26% in pa­tients with sec­ond-line re­cur­rent or metasta­t­ic cer­vi­cal can­cer.

The PD-1/CT­LA-4 com­bo re­port­ed 10 com­plete re­spons­es and 22 par­tial re­spons­es among the study’s mod­i­fied 125-pa­tient pool. Mean­while, the com­bi­na­tion per­formed par­tic­u­lar­ly well in PD-(L)1 pos­i­tive pa­tients, with a 32.8% re­sponse rate among 67 pa­tients, who made up the ma­jor­i­ty of the study’s pop­u­la­tion.

At a six-month check-in, 86.5% of re­spon­ders were still re­spond­ing to treat­ment with com­bo, while at one year that num­ber de­clined to 64.2%. Mean­while the com­bo post­ed a me­di­an over­all sur­vival of 12.8 months at a me­di­an 21-month check-in and a PFS of 2.7 months. For the PD-(L)1 pos­i­tive co­hort, me­di­an OS was 15.7 months.

Agenus called this study group the largest to show ben­e­fit for PD-1/CT­LA-4 block­ade in re­cur­rent or metasta­t­ic cer­vi­cal can­cer, tak­ing a shot right at Bris­tol My­ers Squibb’s com­bo of Op­di­vo and Yer­voy, which turned out da­ta in this pop­u­la­tion back in 2019. In the CHECK­MATE-358 Phase II study, Op­di­vo-Yer­voy post­ed a re­sponse rate of 26.3% among 19 pa­tients with five com­plete and par­tial re­spons­es.

Re­gen­eron’s Lib­tayo looks to match Keytru­da’s com­bo ap­proval in 1L lung can­cer

Re­gen­eron’s Lib­tayo in com­bi­na­tion with chemother­a­py aced its sur­vival end­points as part of the Phase III EM­POW­ER-Lung-3 study in first-line pa­tients with metasta­t­ic non-small cell lung can­cer, with da­ta that look very sim­i­lar to what a Keytru­da-chemo com­bo has al­ready post­ed there.

Lib­tayo-chemo hit a me­di­an OS of 22 months with a me­di­an pro­gres­sion-free sur­vival of 8 months, re­duc­ing the rel­a­tive risk of death by 29% com­pared with a chemo reg­i­men alone. Mean­while, the com­bo post­ed a 43% re­sponse rate com­pared with 23% for chemo and a 16-month du­ra­tion of re­sponse ver­sus sev­en months for chemo.

But Keytru­da has the head­start here, with da­ta from the KEYNOTE-189 study show­ing large­ly the same ef­fi­ca­cy num­bers. The FDA grant­ed the Keytru­da-chemo com­bo an ap­proval here back in Au­gust 2018, adding to its ap­proval as a so­lo agent in the same set­ting.

Seagen, Gen­mab roll out com­bo da­ta for ADC in cer­vi­cal can­cer

Speak­ing of cer­vi­cal can­cer, Seagen and Gen­mab have new da­ta out on their in­ves­ti­ga­tion­al an­ti­body-drug con­ju­gate ti­so­tum­ab ve­dotin (TV) show­ing some strong re­sults in com­bi­na­tion with the chemother­a­py car­bo­platin or Keytru­da across mul­ti­ple lines of ther­a­py for re­cur­rent or metasta­t­ic pa­tients.

Ac­cord­ing to co­hort da­ta from the Phase Ib/II in­no­vaTV 205 study, the TV-car­bo com­bo post­ed a re­sponse rate of 55%, in­clud­ing four com­plete re­spons­es and 14 par­tial re­spons­es, in first-line re­cur­rent or metasta­t­ic cer­vi­cal can­cer pa­tients. At a me­di­an fol­low-up of 7.9 months, the com­bo’s du­ra­tion of re­sponse was 8.3 months with a me­di­an pro­gres­sion-free sur­vival of 9.5 months.

Mean­while, a com­bi­na­tion of TV and Keytru­da in sec­ond- or third-line cer­vi­cal can­cer pa­tients post­ed a 38% re­sponse rate in 34 pa­tients, with two com­plete re­spons­es and 11 par­tial re­spons­es re­port­ed. You’ll re­mem­ber the Phase II KEYNOTE-158 study from a cou­ple years ago post­ed a 17% re­sponse rate for so­lo Keytru­da in pre­vi­ous­ly treat­ed ad­vanced cer­vi­cal can­cer, po­ten­tial­ly point­ing to some ben­e­fit for TV as part of the com­bo.

“As we ad­vance our clin­i­cal de­vel­op­ment pro­gram for ti­so­tum­ab ve­dotin in­to ear­li­er lines of ther­a­py in cer­vi­cal can­cer, we’re en­cour­aged by these in­ter­im re­sults of the com­bi­na­tion co­horts with ti­so­tum­ab ve­dotin,” Seagen CMO Roger Dansey said in a state­ment. “Based on these re­sults from the in­no­vaTV 205 study, we al­so plan to eval­u­ate ti­so­tum­ab ve­dotin fur­ther in var­i­ous com­bi­na­tions in first-line metasta­t­ic or re­cur­rent cer­vi­cal can­cer.”

Mer­ck backs up re­cent Keytru­da ap­proval in TNBC with OS win

A com­bi­na­tion of Keytru­da and chemother­a­py re­duced the risk of death by 27% over chemo alone (p=0.0093) in first-line pa­tients with PD-(L)1 ex­press­ing triple-neg­a­tive breast can­cer, ac­cord­ing to da­ta pre­sent­ed Sun­day.

The com­plete OS re­sults come as a back­stop for the FDA’s ac­cel­er­at­ed nod in this in­di­ca­tion back in No­vem­ber, which was up­grad­ed to a full ap­proval in Ju­ly.

The com­bi­na­tion post­ed a me­di­an OS of 23 months com­pared with 16.1 months for chemo. The agency based its ap­proval on da­ta from the KEYNOTE-355 study, which showed the com­bo re­duced the risk of dis­ease pro­gres­sion or death by 35% with a me­di­an PFS of 9.7 months, against 5.6 months in the chemo arm.

No­var­tis’ Kisqali gets long-await­ed OS read­out in HR+/HER2- breast can­cer

Af­ter wait­ing near­ly five years for the da­ta to ma­ture, No­var­tis can now tout an OS win for its CDK 4/6 in­hibitor in first-line ad­vanced HR+/HER2- breast can­cer, the Swiss drug­mak­er said Sun­day.

At a whop­ping 63.9-month fol­low-up, Kisqali com­bined with the aro­matase in­hibitor letro­zole post­ed a me­di­an OS of 63.9 months com­pared with 51.4 months for letro­zole alone — a more than one-year OS ben­e­fit. No­var­tis is call­ing the OS read­out the longest for a CDK 4/6 and a boon for pa­tients af­ter a very long wait for fi­nal re­sults.

The da­ta come from the MONALEESA-2 tri­al, which was the ba­sis for No­var­tis’ ini­tial ap­proval in this in­di­ca­tion way back in 2017.

Biotech Half­time Re­port: Af­ter a bumpy year, is biotech ready to re­bound?

The biotech sector has come down firmly from the highs of February as negative sentiment takes hold. The sector had a major boost of optimism from the success of the COVID-19 vaccines, making investors keenly aware of the potential of biopharma R&D engines. But from early this year, clinical trial, regulatory and access setbacks have reminded investors of the sector’s inherent risks.

RBC Capital Markets recently surveyed investors to take the temperature of the market, a mix of specialists/generalists and long-only/ long-short investment strategies. Heading into the second half of the year, investors mostly see the sector as undervalued (49%), a large change from the first half of the year when only 20% rated it as undervalued. Around 41% of investors now believe that biotech will underperform the S&P500 in the second half of 2021. Despite that view, 54% plan to maintain their position in the market and 41% still plan to increase their holdings.

So — that pig-to-hu­man trans­plant; Po­ten­tial di­a­betes cure reach­es pa­tient; Ac­cused MIT sci­en­tist lash­es back; and more

Welcome back to Endpoints Weekly, your review of the week’s top biopharma headlines. Want this in your inbox every Saturday morning? Current Endpoints readers can visit their reader profile to add Endpoints Weekly. New to Endpoints? Sign up here.

We’re incredibly excited to welcome Beth Bulik, seasoned pharma marketing reporter, to the team. You can find much of her work in our new Marketing channel — and in her weekly newsletter, Endpoints PharmaRx, which will launch in early November. Add it to your subscriptions here.

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NYU surgeon transplants an engineered pig kidney into the outside of a brain-dead patient (Joe Carrotta/NYU Langone Health)

No, sci­en­tists are not any clos­er to pig-to-hu­man trans­plants than they were last week

Steve Holtzman was awoken by a 1 a.m. call from a doctor at Duke University asking if he could put some pigs on a plane and fly them from Ohio to North Carolina that day. A motorcyclist had gotten into a horrific crash, the doctor explained. He believed the pigs’ livers, sutured onto the patient’s skin like an external filter, might be able to tide the young man over until a donor liver became available.

UP­DAT­ED: Agenus calls out FDA for play­ing fa­vorites with Mer­ck, pulls cer­vi­cal can­cer BLA at agen­cy's re­quest

While criticizing the FDA for what may be some favoritism towards Merck, Agenus on Friday officially pulled its accelerated BLA for its anti-PD-1 inhibitor balstilimab as a potential second-line treatment for cervical cancer because of the recent full approval for Merck’s Keytruda in the same indication.

The company said the BLA, which was due for an FDA decision by Dec. 16, was withdrawn “when the window for accelerated approval of balstilimab closed,” thanks to the conversion of Keytruda’s accelerated approval to a full approval four months prior to its PDUFA date.

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No­vo CEO Lars Fruer­gaard Jør­gensen on R&D risk, the deal strat­e­gy and tar­gets for gen­der di­ver­si­ty


I kicked off our European R&D summit last week with a conversation involving Novo Nordisk CEO Lars Fruergaard Jørgensen. Novo is aiming to launch a new era of obesity management with a new approval for semaglutide. And Jørgensen had a lot to say about what comes next in R&D, how they manage risk and gender diversity targets at the trendsetting European pharma giant.

John Carroll: I’m here with Lars Jørgensen, the CEO of Novo Nordisk. Lars, it’s been a really interesting year so far with Novo Nordisk, right? You’ve projected a new era of growing sales. You’ve been able to expand on the GLP-1 franchise that was already well established in diabetes now going into obesity. And I think a tremendous number of people are really interested in how that’s working out. You have forecast a growing amount of sales. We don’t know specifically how that might play out. I know a lot of the analysts have different ideas, how those numbers might play out, but that we are in fact embarking on a new era for Novo Nordisk in terms of what the company’s capable of doing and what it’s able to do and what it wants to do. And I wanted to start off by asking you about obesity in particular. Semaglutide has been approved in the United States for obesity. It’s an area of R&D that’s been very troubled for decades. There have been weight loss drugs that have come along. They’ve attracted a lot of attention, but they haven’t actually ever gained traction in the market. My first question is what’s different this time about obesity? What is different about this drug and why do you expect it to work now whereas previous drugs haven’t?

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How to col­lect and sub­mit RWD to win ap­proval for a new drug in­di­ca­tion: FDA spells it out in a long-await­ed guid­ance

Real-world data are messy. There can be differences in the standards used to collect different types of data, differences in terminologies and curation strategies, and even in the way data are exchanged.

While acknowledging this somewhat controlled chaos, the FDA is now explaining how biopharma companies can submit study data derived from real-world data (RWD) sources in applicable regulatory submissions, including new drug indications.

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David Livingston (Credit: Michael Sazel for CeMM)

Renowned Dana-Far­ber sci­en­tist, men­tor and bio­phar­ma ad­vi­sor David Liv­ingston has died

David Livingston, the Dana-Farber/Harvard Med scientist who helped shine a light on some of the key molecular drivers of breast and ovarian cancer, died unexpectedly last Sunday.

One of the senior leaders at Dana-Farber during his nearly half century of work there, Livingston was credited with shedding light on the genes that regulate cell growth, with insights into inherited BRCA1 and BRCA2 mutations that helped lay the scientific foundation for targeted therapies and earlier detection that have transformed the field.

Pascal Soriot, AstraZeneca CEO (via Getty images)

UP­DAT­ED: FDA slaps As­traZeneca's MCL-1 can­cer drug with a hold af­ter safe­ty is­sue — 2 years af­ter Am­gen axed a trou­bled ri­val

There are new questions being posed about a class of cancer drugs in the wake of the second FDA-enforced clinical hold in the field.

Two years after the FDA hit Amgen with a clinical hold on its MCL-1 inhibitor AMG 397 following signs of cardiac toxicity, AstraZeneca says that regulators hit them with a hold on their rival therapy of the same class.

The pharma giant noted on that its Phase I/II study for the MCL-1 drug AZD5991 “has been put on hold to allow further evaluation of safety related information.”

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Sur­geons suc­cess­ful­ly at­tach pig kid­ney to a hu­man for the first time, us­ing tech from Unit­ed's Re­vivi­cor

In a first, researchers reportedly successfully transplanted a pig kidney into a human without triggering an immediate immune response this week. And the technology came from the biotech United Therapeutics.

Surgeons spent three days attaching the kidney to the patient’s blood vessels, but when all was said and done, the kidney appeared to be functioning normally in early testing, Reuters and the New York Times were among those to report. The kidney came from a genetically altered pig developed through United’s Revivicor unit.

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