Keytru­da PhI­II fail­ure in gas­tric can­cer blights Mer­ck­'s quest for front­line dom­i­nance

A year and a half af­ter scor­ing an ap­proval to use Keytru­da in third-line gas­tric can­cer, Mer­ck has run in­to a wall try­ing to ap­ply the PD-1 star in the front­line set­ting.

In an up­date for the KEYNOTE-062, the com­pa­ny $MRK dis­closed that Keytru­da as a monother­a­py proved non-in­fe­ri­or to chemother­a­py — the cur­rent stan­dard of care for ad­vanced gas­tric or gas­troe­sophageal junc­tion ade­no­car­ci­no­ma — in over­all sur­vival. In com­bi­na­tion, though, Keytru­da plus chemo was not found to be su­pe­ri­or for ei­ther OS or pro­gres­sion-free sur­vival com­pared with chemo alone. That like­ly meant more miss­es than hits in the pri­ma­ry end­points, list­ed as PFS and OS on clin­i­cal­tri­als.gov.

As a spokesper­son ex­plained:

Based on the pre-spec­i­fied sta­tis­ti­cal analy­sis plan, su­pe­ri­or­i­ty test­ing for OS in the KEYTRU­DA monother­a­py group was con­duct­ed, how­ev­er as an­nounced, the fi­nal analy­sis showed that KEYTRU­DA monother­a­py was non-in­fe­ri­or, not su­pe­ri­or, to the chemother­a­py arm in pa­tients whose tu­mors were CPS ≥1. For KEYNOTE-062, it made sense to test for non­in­fe­ri­or­i­ty in the event that KEYTRU­DA monother­a­py had com­pa­ra­ble ef­fi­ca­cy as chemother­a­py with a po­ten­tial­ly fa­vor­able safe­ty and tol­er­a­bil­i­ty pro­file.

Roy Baynes

Mer­ck went ahead with the Phase III tri­al de­spite a flop in the sec­ond-line set­ting of the same in­di­ca­tion in 2017. Grant­ed, the drug had pos­i­tive third-line da­ta go­ing for it in a tough dis­ease where Pfiz­er and Mer­ck KGaA’s PD-L1 drug Baven­cio failed.

All pa­tients in the tri­al had tu­mors that ex­press PD-L1. In­ves­ti­ga­tors did not tease out any dif­fer­ences be­tween those with a high com­bined pos­i­tive score (CPS ≥10) and those with low CPS, of 1 or above.

“Gas­tric can­cer is his­tor­i­cal­ly dif­fi­cult to treat, and un­for­tu­nate­ly con­tin­ues to be as­so­ci­at­ed with high mor­tal­i­ty rates in many coun­tries, par­tic­u­lar­ly in the metasta­t­ic stage,” said Roy Baynes, Mer­ck’s head of glob­al de­vel­op­ment, in a state­ment.

The brief state­ment al­so didn’t cov­er any of the sec­ondary end­points, in­clud­ing over­all re­sponse rate, du­ra­tion of re­sponse, qual­i­ty of life and a gas­tric can­cer score.

Mer­ck says it plans to dis­cuss the fi­nal analy­sis with the FDA, as well as oth­er on­go­ing gas­tric stud­ies that might serve as con­fir­ma­to­ry tri­als, in­clud­ing KEYNOTE-811 and KEYNOTE-859. Then there’s the Phase III KEYNOTE-585 to watch, where Keytru­da in com­bi­na­tion with chemother­a­py is test­ed in a neoad­ju­vant/ad­ju­vant set­ting.

Op­ti­miz­ing Cell and Gene Ther­a­py De­vel­op­ment and Pro­duc­tion: How Tech­nol­o­gy Providers Like Corn­ing Life Sci­ences are Spurring In­no­va­tion

Remarkable advances in cell and gene therapy over the last decade offer unprecedented therapeutic promise and bring new hope for many patients facing diseases once thought incurable. However, for cell and gene therapies to reach their full potential, researchers, manufacturers, life science companies, and academics will need to work together to solve the significant challenges facing the industry.

Amid mon­key­pox fears, biotechs spring to ac­tion; Mod­er­na’s CFO trou­ble; Cuts, cuts every­where; Craft­ing the right pro­teins; and more

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It’s always a bittersweet moment saying goodbye, but as Josh Sullivan goes off to new adventures we are grateful for the way he’s built up the Endpoints Manufacturing section — which the rest of the team will now carry forward. If you’re not already, this may be a good time to sign up for your weekly dose of drug manufacturing news. Thank you for reading and wish you a restful weekend.

Bay­er sounds re­treat from a $670 mil­lion CAR-T pact in the wake of a pa­tient death

Two months after Atara Biotherapeutics hit the hold button on its lead CAR-T 2.0 therapy following a patient death, putting the company under the watchful eye of the FDA, its Big Pharma partners at Bayer are bowing out of a $670 million global alliance. And the move is forcing a revamp of Atara’s pipeline plans, even as research execs vow to continue work on the two drugs allied with Bayer 18 months ago, which delivered a $60 million cash upfront.

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Sanofi and Re­gen­eron clear the fin­ish line in an in­flam­ma­to­ry esoph­a­gus dis­ease, leav­ing Take­da in the dust

With atopic dermatitis rivals breathing down Dupixent’s neck, Sanofi and Regeneron on Friday secured a first win in new territory in what Sanofi’s head of immunology and inflammation Naimish Patel called the fastest approval he’s ever seen.

The FDA approved Dupixent on Friday to treat patients 12 years and older with eosinophilic esophagitis (EoE), an inflammatory condition that causes swelling and scarring of the esophagus. The approval came just a couple months after regulators granted Dupixent priority review, and months ahead of its PDUFA date on Aug. 3.

Fu­ji­film con­tin­ues its biotech build­ing spree with new fa­cil­i­ty in Chi­na

A Japanese conglomerate is making a big play in China with the opening of a new facility, as it continues to expand.

Fujifilm Irvine Scientific has opened its new Innovation and Collaboration Center in Suzhou New District, China, an area in Jiangsu province specifically designated for technological and industrial development.

According to Fujifilm, the 12,000-square-foot site will be responsible for the company’s cell culture media optimization, analysis and design services. Cell culture media itself often requires customization of formulas and protocols to achieve the desired quantity and quality of therapeutic desired. Fujifilm Irvine Scientific is offering these services from its headquarters in California and Japan to its customers globally, as well as in China now.

Try­ing to shake up the Parkin­son's par­a­digm, Ab­b­Vie sub­mits NDA for con­tin­u­ous, 24-hour in­fu­sion ther­a­py

AbbVie is approaching the FDA with a new therapy to potentially treat Parkinson’s disease, using prodrugs of two medications commonly used for the condition.

The Big Pharma submitted its NDA for ABBV-951, a solution of levodopa and carbidopa prodrugs being evaluated in advanced Parkinson’s patients who don’t respond well to oral therapy, AbbVie announced Friday morning. Researchers are hoping a positive Phase III study that reads out in late October will help move things along quickly at the agency.

Rob Etherington, Clene CEO

Mary­land of­fers loan to Clene de­spite ALS tri­al bumps

Even after Utah-based Clene failed to hit its primary endpoints for its ALS drug last year, the state of Maryland is putting its money at least behind Clene’s manufacturing facility.

The Maryland Board of Public Works has finalized a $3 million, 60-month loan facility with Clene Nanomedicine. The loan was provided by the state’s Neighborhood BusinessWorks program within the Maryland Department of Housing and Community Development.

Armon Sharei, SQZ founder and CEO

SQZ's out­side-the-box man­u­fac­tur­ing method slash­es pro­duc­tion time in ear­ly in study

At ASCO 2021 in June of last year, SQZ Biotech showcased a glimpse of its unorthodox cell therapy manufacturing tech. And on Wednesday, the Watertown, MA, company announced that its first-generation system showed comparable or better performance than a conventional clean-room-based manufacturing process.

The study was non-clinical. Clinical trials are expected by the first half of 2023.

SQZ’s device opens up a temporary window by cell-squeezing to deliver cargoes into cells. Its average processing time was less than six hours per batch, which is more than half the time than conventional methods. The company is planning to use the technology in its first red blood cell derived program for celiac disease. That IND is set to be submitted in the first half of 2023, the company said.

Bobby Sheng, Bora Pharmaceuticals CEO

With new ac­qui­si­tion, Bo­ra to ven­ture in­to bi­o­log­ics

Last week, Taiwan-based CDMO Bora Pharmaceuticals announced that it acquired Eden Biologics. Now, it says that purchase has helped established Bora Biologics, expanding into the biopharmaceutical market.

The acquisition of the company’s assets, which are located in the Hsinchu Biomedical Science Park in Taiwan, is helping Bora build its presence in the biopharma world by expanding production capacity of cell lines for the production of protein drugs. It will also improve the quality control and inspection specifications, as well as cell bank generation. The facility has four 500-liter bioreactors that have been approved by European and Taiwanese regulators.