Check­point com­bos for can­cer are all the rage as tri­al spon­sors line up hun­dreds of new stud­ies — re­port

Num­ber of An­ti-PD-1/PD-L1 MAb com­bi­na­tion stud­ies 2015 vs. 2017
Full Re­port: Eval­u­ate Ltd. May 2017


Over the last few months it hasn’t been un­usu­al to see new com­bi­na­tion stud­ies be­ing an­nounced on a dai­ly ba­sis, match­ing one of the 5 ap­proved PD-(L)1 check­point drugs with an­oth­er can­cer ther­a­py. Some morn­ings they come in pairs.

It’s not hard to see why. The check­points typ­i­cal­ly work as a monother­a­py — though there have been some nasty set­backs over the past 6 months. And some of the big play­ers are hap­py to con­tribute their drug to stud­ies spon­sored by oth­ers look­ing to ad­vance a pi­lot Phase I/II ex­plorato­ry study. There are al­so re­cent ex­am­ples of some big tie-ups be­tween Mer­ck (Keytru­da) and Bris­tol-My­ers Squibb (Op­di­vo) check­points with In­cyte in Phase III.

In­cyte has its own PD-1 in the clin­ic as it lines up these ag­nos­tic late-stage tri­als to po­si­tion its lead­ing IDO1 drug.

Now EP Van­tage has tal­lied the whole score on these com­bo tri­als, not co­in­ci­den­tal­ly just ahead of AS­CO, and found a stun­ning 765 com­bi­na­tion stud­ies list­ed on clin­i­cal­tri­als.gov. Keytru­da leads the pack, with 268 — up from 70 just 18 months ago. For Bris­tol-My­ers it’s 242, more than three times the num­ber EP Van­tage’s ed­i­to­r­i­al team found in 2015.

Any­one even mod­er­ate­ly in­ter­est­ed in this field will want to check it out di­rect­ly. There’s a lot of de­tail on what’s now in the clin­ic.

Don’t ex­pect the ris­ing trend lines to start to plateau any­time soon, ei­ther, as Pfiz­er/Mer­ck KGaA (Baven­cio) and As­traZeneca (Imfinzi) start to gain trac­tion on the com­bo front. Roche al­ready emerged as the num­ber three play­er in the field with Tecen­triq, though its re­cent Phase III fail­ure for its check­point may chill oth­er would-be part­ners.

Mean­while, new check­point play­ers like BeiGene and Lil­ly are mov­ing along, the re­port notes, while No­var­tis has been ad­vanc­ing its own in-house check­point pro­grams. The sec­ond wave of PD-(L)1 ther­a­pies will be large.

One of the key next steps in this field is in As­traZeneca’s hands. It has a com­bo of Imfinzi with an in-house CT­LA-4 check­point dubbed treme­li­mum­ab in the MYS­TIC study that will read out soon for lung can­cer. An­a­lysts are wait­ing ea­ger­ly to see if it can beat out the com­pe­ti­tion, or get side­lined by some well-known tox­i­c­i­ty con­cerns.

One thing is ab­solute­ly cer­tain. Bris­tol-My­ers Squibb start­ed as the dom­i­nant play­er in PD-(L)1, then got checked by a surg­ing Mer­ck when it made the wrong clin­i­cal move on non-small cell lung can­cer. As­traZeneca, the last of the big 5 to land an ap­proval, just days ago stunned vir­tu­al­ly every­one with pos­i­tive Phase III da­ta for Imfinzi in un­re­sectable lung can­cer, pro­vid­ing ear­ly dom­i­nance in a sig­nif­i­cant niche mar­ket.

The Big Phar­ma’s stock soared as an­a­lysts be­gan to cal­cu­late what that is worth.

Just at a time when check­points should start get­ting more pre­dictable, the field seems to be ripe for fresh sur­pris­es of all kinds. And that will con­tin­ue to at­tract fresh waves of com­bi­na­tion stud­ies tack­ling all kinds of can­cers.

ZS Per­spec­tive: 3 Pre­dic­tions on the Fu­ture of Cell & Gene Ther­a­pies

The field of cell and gene therapies (C&GTs) has seen a renaissance, with first generation commercial therapies such as Kymriah, Yescarta, and Luxturna laying the groundwork for an incoming wave of potentially transformative C&GTs that aim to address diverse disease areas. With this renaissance comes several potential opportunities, of which we discuss three predictions below.

Allogenic Natural Killer (NK) Cells have the potential to displace current Cell Therapies in oncology if proven durable.

Despite being early in development, Allogenic NKs are proving to be an attractive new treatment paradigm in oncology. The question of durability of response with allogenic therapies is still an unknown. Fate Therapeutics’ recent phase 1 data for FT516 showed relatively quicker relapses vs already approved autologous CAR-Ts. However, other manufacturers, like Allogene for their allogenic CAR-T therapy ALLO-501A, are exploring novel lymphodepletion approaches to improve persistence of allogenic cells. Nevertheless, allogenic NKs demonstrate a strong value proposition relative to their T cell counterparts due to comparable response rates (so far) combined with the added advantage of a significantly safer AE profile. Specifically, little to no risk of graft versus host disease (GvHD), cytotoxic release syndrome (CRS), and neurotoxicity (NT) have been seen so far with allogenic NK cells (Fig. 1). In addition, being able to harness an allogenic cell source gives way to operational advantages as “off-the-shelf” products provide improved turnaround time (TAT), scalability, and potentially reduced cost. NKs are currently in development for a variety of overlapping hematological indications with chimeric antigen receptor T cells (CAR-Ts) today, and the question remains to what extent they will disrupt the current cell therapy landscape. Click for more details.

Graphic: Kathy Wong for Endpoints News

What kind of biotech start­up wins a $3B syn­di­cate, woos a gallery of mar­quee sci­en­tists and re­cruits GSK's Hal Bar­ron as CEO in a stun­ner? Let Rick Klaus­ner ex­plain

It started with a question about a lifetime’s dream on a walk with tech investor Yuri Milner.

At the beginning of the great pandemic, former NCI chief and inveterate biotech entrepreneur Rick Klausner and the Facebook billionaire would traipse Los Altos Hills in Silicon Valley Saturday mornings and talk about ideas.

Milner’s question on one of those mornings on foot: “What do you want to do?”

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Executive Director of the EMA Emer Cooke (AP Photo/Geert Vanden Wijngaert)

Eu­ro­pean Par­lia­ment signs off on strength­en­ing drug reg­u­la­tor's abil­i­ty to tack­le short­ages

The European Parliament on Thursday endorsed a plan to increase the powers of the European Medicines Agency, which will be better equipped to monitor and mitigate shortages of drugs and medical devices.

By a vote of 655 to 31, parliament signed off on a provisional agreement reached with the European Council from last October, in which the EMA will create two shortage steering groups (one for drugs, the other for devices), a new European Shortages Monitoring Platform to facilitate data collection and increase transparency, and on funding for the work of the steering groups, task force, working parties and expert panels that are to be established.

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Sec­ondary patents prove to be key in biosim­i­lar block­ing strate­gies, re­searchers find

While the US biosimilars industry has generally been a disappointment since its inception, with FDA approving 33 biosimilars since 2015, just a fraction of those have immediately followed their approvals with launches. And more than a handful of biosimilars for two of the biggest blockbusters of all time — AbbVie’s Humira and Amgen’s Enbrel — remain approved by FDA but still have not launched because of legal settlements.

Hal Barron, Endpoints UKBIO20 (Jeff Rumans)

'Al­tos was re­al­ly a once-in-a-life­time op­por­tu­ni­ty': Hal Bar­ron re­flects on his big move

By all accounts, Hal Barron had one of the best jobs in Big Pharma R&D. He made more than $11 million in 2020, once again reaping more than his boss, Emma Walmsley, who always championed him at every opportunity. And he oversaw a global R&D effort that struck a variety of big-dollar deals for oncology, neurodegeneration and more.

Sure, the critics never let up about what they saw as a rather uninspiring late-stage pipeline, where the rubber hits the road in the Big Pharma world’s hunt for the next big near-term blockbuster, but the in-house reviews were stellar. And Barron was firmly focused on bringing up the success rate in clinical trials, holding out for the big rewards of moving the dial from an average 10% success rate to 20%.

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Kenneth Galbraith, incoming Zymeworks CEO

Zymeworks re­places half its C-suite, aims to lay off 25% of to­tal work­force as new CEO takes over

New Zymeworks CEO Kenneth Galbraith is aiming to hit the ground running when his tenure officially begins next month, but he’ll be doing so with a much different looking team.

In a lengthy press release outlining the biotech’s 2022 goals, Galbraith said Zymeworks will be laying off at least 25% of its staff over the course of the year. Half of its C-suite will also be replaced immediately as Galbraith looks to remake the company in his image after Ali Tehrani, Zymeworks’ founder and CEO since 2003, stepped down two weeks ago.

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FDA+ roundup: FDA's neu­ro­science deputy de­parts amid on­go­ing Aduhelm in­ves­ti­ga­tions; Califf on the ropes?

Amid increased scrutiny into the close ties between FDA and Biogen prior to the controversial accelerated approval of Aduhelm, the deputy director of the FDA’s office of neuroscience has called it quits after more than two decades at the agency.

Eric Bastings will now take over as VP of development strategy at Ionis Pharmaceuticals, the company said Wednesday, where he will provide senior clinical and regulatory leadership in support of Ionis’ pipeline.

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Hal Barron (GSK via YouTube)

GSK R&D chief Hal Bar­ron jumps ship to run a $3B biotech start­up, Tony Wood tapped to re­place him

In a stunning switch, GlaxoSmithKline put out word early Wednesday that R&D chief Hal Barron is exiting the company after 4 years — a relatively brief run for the man chosen by CEO Emma Walmsley in late 2017 to turn around the slow-footed pharma giant.

Barron is being replaced by Tony Wood, a close associate of Barron’s who’s taking one of the top jobs in Big Pharma R&D. He’ll be closer to home, though, for GSK. Barron has been running a UK and Philadelphia-based research organization from his perch in San Francisco.

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CBO: Medicare ne­go­ti­a­tions will ham­per drug de­vel­op­ment more than pre­vi­ous­ly thought

As President Biden’s Build Back Better Act — and, with it, potentially the Democrats’ last shot at major drug pricing reforms in the foreseeable future — remains on life support, the Congressional Budget Office isn’t helping their case.

The CBO last week released a new slide deck, outlining an update to its model on how Medicare negotiations might take a bite out of new drugs making it to market. The new model estimates a 10% long-term reduction in the number of new drugs, whereas a previous CBO report from August estimated that 8% fewer new drugs will enter the market over 30 years.