Im­munomedics spells out PFS ben­e­fit of Trodelvy in mTNBC, hunt­ing a full OK just weeks af­ter ac­cel­er­at­ed ap­proval

By the time the FDA fi­nal­ly grant­ed an ac­cel­er­at­ed OK for Im­munomedics’ Trodelvy, we al­ready got a very strong hint that their con­fir­ma­to­ry Phase III study in metasta­t­ic triple-neg­a­tive breast can­cer was a suc­cess.

That’s be­cause the in­de­pen­dent da­ta safe­ty mon­i­tor­ing com­mit­tee rec­om­mend­ed that the tri­al be stopped ear­ly. But just what point­ed them to the con­clu­sion was still un­clear.

Be­hzad Ag­haz­adeh

“We do not know the to­tal­i­ty of their de­ci­sion oth­er than it’s pret­ty ev­i­dent that the pri­ma­ry end­point was met; oth­er­wise they could not re­quest to halt the study,” Be­hzad Ag­haz­adeh, the ex­ec­u­tive chair­man, told End­points News at the time.

Three months lat­er, Im­munomedics has de­tailed the re­sults from AS­CENT, in­clud­ing pro­gres­sion-free sur­vival and over­all sur­vival da­ta that the prin­ci­pal in­ves­ti­ga­tor said “set a new bench­mark” in mTNBC.

PFS was the pri­ma­ry end­point, and Trodelvy — an an­ti­body-drug con­ju­gate known as sac­i­tuzum­ab govite­can — kept the can­cer at bay (and pa­tients from dy­ing) for a me­di­an of 5.6 months, com­pared to 1.7 months on chemother­a­py (p<0.0001). The haz­ard ra­tio reg­is­tered at 0.41.

Shares $IM­MU rose 6.67% to $40.04.

Im­munomedics stopped short of spelling out the OS win, but not­ed that and oth­er key sec­ondary end­points such as ob­jec­tive re­sponse rate were met.

Aditya Bar­dia

“Im­por­tant­ly, the AS­CENT topline da­ta al­so val­i­date the man­age­able safe­ty pro­file of sac­i­tuzum­ab govite­can, ren­der­ing it a good part­ner can­di­date for com­bi­na­tion with oth­er ther­a­pies, in­clud­ing im­munother­a­py,” Aditya Bar­dia, the prin­ci­pal in­ves­ti­ga­tor and di­rec­tor of pre­ci­sion med­i­cine at Mass Gen­er­al’s Cen­ter for Breast Can­cer, said.

Trodelvy was ap­proved, with a black box warn­ing for se­vere neu­trope­nia and se­vere di­ar­rhea, as a third-line treat­ment for mTNBC, a tough-to-treat can­cer as­so­ci­at­ed with poor prog­no­sis. The new da­ta are ex­pect­ed to sup­port a full OK.

“It is grat­i­fy­ing to see the fi­nal con­fir­ma­to­ry re­sults of Trodelvy in a ran­dom­ized study sup­port­ing the pre­vi­ous­ly re­port­ed Phase 2 da­ta that formed the ba­sis of the ac­cel­er­at­ed ap­proval of Trodelvy,” Ag­haz­adeh, who has been run­ning the show since Michael Pehl left the helm ear­ly 2019 in the wake of an FDA re­jec­tion, said in a state­ment.

No­var­tis On­col­o­gy vet and Ipsen alum Harout Se­mer­jian came on board briefly as CEO in April, on­ly to de­part less than two months lat­er as the pan­dem­ic cre­at­ed in­sur­mount­able chal­lenges for mov­ing his fam­i­ly from Lon­don.

The hic­cup hasn’t dent­ed Cowen an­a­lyst Phil Nadeau’s high ex­pec­ta­tions of the ther­a­py, which his con­sul­tants said will be rapid­ly adopt­ed as the stan­dard in re­lapsed or re­frac­to­ry mTNBC, bring­ing in $1 bil­lion in world­wide rev­enue by 2025 (Ever­est Med­i­cines is han­dling the de­vel­op­ment and com­mer­cial­iza­tion in Chi­na). Ac­cord­ing to Nadeau, the num­bers hit the “up­per end of ex­pec­ta­tions.”

“In­vestors an­tic­i­pat­ed that Trodelvy would pro­duce a me­di­an PFS of 5-5.5 months con­sis­tent with its Ph. I/II, but our sense is that most an­tic­i­pat­ed a me­di­an PFS for chemother­a­py of 2.5-3 months,” he wrote.

And that’s not tak­ing in­to ac­count its po­ten­tial in ER+/HER2- metasta­t­ic breast can­cer or urothe­lial car­ci­no­ma, which now seems even more like­ly giv­en the pos­i­tive AS­CENT da­ta.

“In­vestors un­der­es­ti­mate the sales po­ten­tial of Trodelvy,” he wrote in a re­cent note. “Trodelvy’s da­ta sug­gest it is a sim­i­lar im­prove­ment over the stan­dard of care in r/r ER+/HER2- mBC as it is in mTNBC, and there are ap­prox. 3-4x as many women with r/r ER+/HER2- mBC. This mar­ket is a $3-4B op­por­tu­ni­ty for Trodelvy, not yet ful­ly re­flect­ed in es­ti­mates or in IM­MU’s val­u­a­tion, de­spite po­ten­tial­ly piv­otal da­ta an­tic­i­pat­ed around YE.”

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.