Ali Tehrani, Zymeworks CEO

Zymeworks squares up with Her­ceptin af­ter HER2 bis­pe­cif­ic aces mid-stage test in esophageal can­cer

Roche’s Her­ceptin has long stood as stan­dard of care across mul­ti­ple ad­vanced can­cers, but a suite of next-gen play­ers are look­ing to beat the ag­ing gi­ant at its own game. In HER2-ex­press­ing esophageal can­cer, BeiGene part­ner Zymeworks thinks its bis­pe­cif­ic an­ti­body could have the juice to get it done.

Zymeworks’ bis­pe­cif­ic an­ti­body zanidatam­ab, com­bined with one of two chemother­a­py reg­i­mens, post­ed an over­all re­sponse rate of 75% in pa­tients with ad­vanced gas­troe­sophageal ade­no­car­ci­no­ma (GEA) who had not pre­vi­ous­ly re­ceived a HER2-tar­get­ed can­cer ther­a­py, the Van­cou­ver-based biotech said Thurs­day.

The re­sults from the Phase II study are set to be pre­sent­ed at this week­end’s #ES­MO21 and look to set the bat­tle lines be­tween Zymeworks and part­ner BeiGene and Her­ceptin, the long­time stan­dard of care in first-line ad­vanced esophageal can­cer.

Zymeworks in­tends to pur­sue a Phase III study based on these re­sults look­ing in par­tic­u­lar at the com­bi­na­tion of zanidatam­ab and the chemo reg­i­men known as CAPOX/FP. That com­bo post­ed a re­sponse rate of 93% in the Phase II study, which the part­ners see as a po­ten­tial strong con­tender against Her­ceptin in this set­ting for the first time in years.

Mean­while, the me­di­an du­ra­tion of re­sponse was 16.4 months with a me­di­an pro­gres­sion-free sur­vival of one year across all pa­tients, Zymeworks said. At the cut­off, 61% of pa­tients were still in the study.

Zymeworks thinks those ef­fi­ca­cy and dura­bil­i­ty da­ta stack up well against what Her­ceptin has shown in its own tri­als. In the Phase III TO­GA tri­al, Her­ceptin plus chemo post­ed a 47.3% re­sponse rate in gas­tric or gas­troe­sophageal junc­tion can­cers with a me­di­an PFS of around 7 months. Those re­sults would ap­pear to give zanidatam­ab the clear lead, but it’s im­por­tant to note the da­ta in Zymeworks’ open-la­bel study were not pow­ered for ef­fi­ca­cy and the pool was fair­ly small — 36 pa­tients to­tal and 28 evalu­able. A Phase III test, how­ev­er, will put those re­sults to the test.

That planned study, dubbed HER­I­ZON-GEA-01, is set to open in the fourth quar­ter, and will test the zanidatam­ab-CAPOX com­bo with or with­out No­var­tis and BeiGene’s PD-1 in­hibitor tislelizum­ab in a head-to-head matchup with the Her­ceptin-chemo stan­dard of care in first-line ad­vanced GEA.

Mean­while, Zymeworks is al­so keep­ing an eye on evolv­ing stan­dard of care in this set­ting, with Mer­ck and Roche’s col­lab­o­ra­tion on Keytru­da plus Her­ceptin plus chemo in first-line esophageal can­cer in the KEYNOTE-811 study cur­rent­ly on­go­ing. Zymeworks has its own Phase II study look­ing at zanidatam­ab plus chemo and PD-1 to keep up, but thinks its da­ta with or with­out PD-1 can stack up well.

The rise of bis­pe­cif­ic an­ti­bod­ies, an old-school drug con­cept that has on­ly re­cent­ly caught on with the FDA, has raised the prospect of chal­leng­ing long-stand­ing stan­dards of care in ad­vanced can­cers, and zanidatam­ab’s case is no dif­fer­ent. The drug, known as a “HER2xHER2” bis­pe­cif­ic, works by si­mul­ta­ne­ous­ly bind­ing two non-over­lap­ping HER2 epi­topes — ECD2 and ECD4 — ef­fec­tive­ly of­fer­ing a dou­ble down ap­proach to tar­get­ing that well-known tu­mor tar­get.

Zymeworks thinks zanidatam­ab could have a par­tic­u­lar­ly strong ef­fect in HER2 over­ex­pressers, which make up just 20% of ad­vanced GAE pa­tients.

Back in No­vem­ber, the FDA of­fered a break­through des­ig­na­tion for the drug in pre­vi­ous­ly-treat­ed HER2 gene-am­pli­fied bil­iary tract can­cer based on the strength of its Phase I da­ta.

The Price of Re­lief: Ex­plor­ing So­lu­tions to the Ris­ing Costs of On­col­o­gy Drugs

In 2020, The National Cancer Institute estimated about 1.8 million new cases of cancer diagnosed in the United States, while the costs associated with treatment therapies continued to escalate. Given the current legislative climate on drug pricing, it’s never been more important to look at the evolution of drug pricing globally and control concerns of sustainable and affordable treatments in oncology.

Lat­est news on Pfiz­er's $3B+ JAK1 win; Pacts over M&A at #JPM22; 2021 by the num­bers; Bio­gen's Aduhelm reck­on­ing; The sto­ry of sotro­vimab; 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.

For those of you who attended #JPM22 in any shape or form, we hope you had a fruitful time. Regardless of how you spent the past hectic week, may your weekend be just what you need it to be.

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Susan Galbraith, AstraZeneca EVP, Oncology R&D

Can­cer pow­er­house As­traZeneca rolls the dice on a $75M cash bet on a buzzy up­start in the on­col­o­gy field

After establishing itself in the front ranks of cancer drug developers and marketers, AstraZeneca is putting its scientific shoulder — and a significant amount of cash — behind the wheel of a brash new upstart in the biotech world.

The pharma giant trumpeted news this morning that it is handing over $75 million upfront to ally itself with Scorpion Therapeutics, one of those biotechs that was newly birthed by some top scientific, venture and executive talent and bequeathed with a fortune by way of a bankroll to advance an only hazily explained drug platform. And they are still very much in the discovery and preclinical phase.

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A $3B+ peak sales win? Pfiz­er thinks so, as FDA of­fers a tardy green light to its JAK1 drug abroc­i­tinib

Back in the fall of 2020, newly crowned Pfizer chief Albert Bourla confidently put their JAK1 inhibitor abrocitinib at the top of the list of blockbuster drugs in the late-stage pipeline with a $3 billion-plus peak sales estimate.

Since then it’s been subjected to serious criticism for the safety warnings associated with the class, held back by a cautious FDA and questioned when researchers rolled out a top-line boast that their heavyweight contender had beaten the champ in the field of atopic dermatitis — Dupixent — in a head-to-head study.

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Robert Califf, FDA commissioner nominee (Graeme Sloan/Sipa USA/Sipa via AP Images)

Rob Califf ad­vances as Biden's FDA nom­i­nee, with a close com­mit­tee vote

Rob Califf’s second confirmation process as FDA commissioner is already much more difficult than his near unanimous confirmation under the Obama administration.

The Senate Health Committee on Thursday voted 13-8 in favor of advancing Califf’s nomination to a full Senate vote. Several Democrats voted against Califf, including Sen. Bernie Sanders and Sen. Maggie Hassan. Several other Democrats who aren’t on the committee, like West Virginia’s Joe Manchin and Ed Markey of Massachusetts, also said Thursday that they would not vote for Califf. Markey, Hassan and Manchin all previously expressed reservations about the prospect of Janet Woodcock as an FDA commissioner nominee too.

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Michel Vounatsos, Biogen CEO (World Economic Forum/Ciaran McCrickard)

Bio­gen vows to fight CM­S' draft cov­er­age de­ci­sion for Aduhelm be­fore April fi­nal­iza­tion

Biogen executives made clear in an investor call Thursday they are not preparing to run a new CMS-approved clinical trial for their controversial Alzheimer’s drug anytime soon.

As requested in a draft national coverage decision from CMS earlier this week, Biogen and other anti-amyloid drugs will need to show “a meaningful improvement in health outcomes” for Alzheimer’s patients in a randomized, placebo-controlled trial to get paid for their drugs, rather than just the reduction in amyloid plaques that won Aduhelm its accelerated approval in June.

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CRO own­er pleads guilty to ob­struct­ing FDA in­ves­ti­ga­tion in­to fal­si­fied clin­i­cal tri­al da­ta

The co-owner of a Florida-based clinical research site pleaded guilty to lying to an FDA investigator during a 2017 inspection, revealing that she falsely portrayed part of a GlaxoSmithKline pediatric asthma study as legitimate, when in fact she knew that certain data had been falsified, the Department of Justice said Wednesday.

Three other employees — Yvelice Villaman Bencosme, Lisett Raventos and Maytee Lledo — previously pleaded guilty and were sentenced in connection with falsifying data associated with the trial at the CRO Unlimited Medical Research.

‘Skin­ny la­bels’ on gener­ics can save pa­tients mon­ey, re­search shows, but re­cent court de­ci­sions cloud fu­ture

New research shows how generic drug companies can successfully market a limited number of approved indications for a brand name drug, prior to coming to market for all of the indications. But several recent court decisions have created a layer of uncertainty around these so-called “skinny” labels.

While courts have generally allowed generic manufacturers to use their statutorily permitted skinny-label approvals, last summer, a federal circuit court found that Teva Pharmaceuticals was liable for inducing prescribers and patients to infringe GlaxoSmithKline’s patents through advertising and marketing practices that suggested Teva’s generic, with its skinny label, could be employed for the patented uses.

A patient in Alaska receiving an antibody infusion to prevent Covid hospitalizations in September. All but one of these treatments has been rendered useless by Omicron (Rick Bowmer/AP Images)

How a tiny Swiss lab and two old blood sam­ples cre­at­ed one of the on­ly ef­fec­tive drugs against Omi­cron (and why we have so lit­tle of it)

Exactly a decade before a novel coronavirus broke out in Wuhan, Davide Corti — a newly-minted immunologist with frameless glasses and a quick laugh — walked into a cramped lab on the top floor of an office building two hours outside Zurich. He had only enough money for two technicians and the ceiling was so low in parts that short stature was a job requirement, but Corti believed it’d be enough to test an idea he thought could change medicine.

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