Ex­elix­is, Bris­tol-My­ers mount piv­otal study of Cabo/Op­di­vo com­bo for front­line kid­ney can­cer

Fouad Namouni, Bris­tol-My­ers Squibb

Just days af­ter re­view­ing a promis­ing start com­bin­ing Bris­tol-My­ers Squibb’s check­point in­hibitor Op­di­vo (nivolum­ab) with Cabome­tyx (cabozan­ti­nib), Ex­elix­is is rolling out a late-stage part­ner­ship that will take the com­bo in­to a piv­otal Phase III study as a front­line ther­a­py for kid­ney can­cer. And not sat­is­fied with the one check­point tie-up, the South San Fran­cis­co-based biotech al­so an­nounced a deal this morn­ing to col­lab­o­rate with Roche on a com­bi­na­tion of its drug Tecen­triq (ate­zolizum­ab) and cabo.

Ex­elix­is $EX­EL and Bris­tol-My­ers $BMY are split­ting the costs on their Phase III pro­gram, which will ex­plore the com­bo, ei­ther alone or with Yer­voy (ip­il­i­mum­ab), in kid­ney can­cer as well as blad­der can­cer, he­pa­to­cel­lu­lar car­ci­no­ma and pos­si­bly oth­er tu­mor types. The ear­ly stage work was done un­der an agree­ment with the NCI’s Can­cer Ther­a­py Eval­u­a­tion Pro­gram. This new pact marks Ex­elix­is’ and Bris­tol-My­ers’ first R&D col­lab­o­ra­tion in I/O.

Ex­elix­is shares jump 6% on the news.

Ten days ago Ex­elix­is un­veiled the first snap­shot of ef­fi­ca­cy da­ta for the dou­ble and triple com­bo in gen­i­touri­nary tu­mors.

In­ves­ti­ga­tors con­clud­ed:

Among the 43 pa­tients who were evalu­able for re­sponse, the ob­jec­tive re­sponse rate (ORR) for all tu­mor types was 30 per­cent (38 per­cent for the dou­blet dos­ing sched­ule and 18 per­cent for the triplet dos­ing sched­ule), with a 7 per­cent com­plete re­sponse (CR) rate and a 23 per­cent par­tial re­sponse (PR) rate. Sta­ble dis­ease (SD) was re­port­ed in 56 per­cent of pa­tients. The ORR for pa­tients with mUC was 38 per­cent, and 2 of 16 pa­tients achieved a CR, while 2 pa­tients with squa­mous cell car­ci­no­ma of the blad­der had ob­jec­tive re­spons­es (1 CR and 1 PR). In the mUC co­hort, 15 of 16 pa­tients had a CR, PR or SD as their best re­sponse.

“Com­bin­ing our Im­muno-On­col­o­gy port­fo­lio with promis­ing agents which tar­get dif­fer­ent and com­ple­men­tary path­ways is a key com­po­nent of our strat­e­gy to im­prove treat­ment out­comes for pa­tients,” said Fouad Namouni, MD, head of De­vel­op­ment, On­col­o­gy, Bris­tol-My­ers Squibb.

Bris­tol-My­ers — the one-time leader in check­point in­hibitors — is con­tin­u­ing to dou­ble down on Op­di­vo af­ter an em­bar­rass­ing se­ries of set­backs in lung can­cer bad­ly dent­ed its share price.

Leerink’s Michael Schmidt gave the deal a quick thumbs up, hap­py to see Ex­elix­is take a shot at mov­ing to front­line use.

This is pos­i­tive news since these col­lab­o­ra­tions could po­ten­tial­ly sig­nif­i­cant­ly ex­pand Cabome­tyx com­mer­cial po­ten­tial be­yond 2nd lien RCC, while lim­it­ing ad­di­tion­al in­cre­men­tal R&D spend which is in-line with mgmt.’s busi­ness strat­e­gy. While some of the Cabome­tyx opp’ty be­yond the cur­rent­ly ap­proved in­di­ca­tion in 2nd line RCC is re­flect­ed in our mod­el and val­u­a­tion, the scope of these col­lab­o­ra­tions ex­ceeds our ex­pec­ta­tions and could po­ten­tial­ly in­crease the reg­u­la­to­ry and com­mer­cial prob­a­bil­i­ty-of-suc­cess for Cabome­tyx in 1st line RCC. Our es­ti­mates are un­der re­view.

Ex­elix­is is al­so spon­sor­ing a Phase Ib study that pairs cabo with Tecen­triq in fight­ing sol­id tu­mors. With en­roll­ment planned to be­gin in the mid­dle of this year, in­ves­ti­ga­tors have a shot at lat­er open­ing up four treat­ment co­horts: one for pre­vi­ous­ly un­treat­ed ad­vanced clear cell re­nal cell car­ci­no­ma and three co­horts of urothe­lial car­ci­no­ma, in­clud­ing plat­inum el­i­gi­ble first-line pa­tients, first- or sec­ond-line plat­inum in­el­i­gi­ble pa­tients and pa­tients pre­vi­ous­ly treat­ed with plat­inum-con­tain­ing chemother­a­py.

The da­ta from these stud­ies can be made avail­able to Ex­elix­is’ part­ners, Ipsen and Take­da, for their own de­vel­op­ment ini­tia­tives, pro­vid­ed they opt in. So far though on­ly Ipsen has signed up.

“Peo­ple with ad­vanced gen­i­toruri­nary ma­lig­nan­cies are in need of ad­di­tion­al treat­ment op­tions that can im­prove clin­i­cal out­comes,” said Suman­ta Ku­mar Pal, MD, co-di­rec­tor, Kid­ney Can­cer Pro­gram at City of Hope, and prin­ci­pal in­ves­ti­ga­tor in the study. “The com­bined ap­proach of ty­ro­sine ki­nase in­hi­bi­tion with cabozan­ti­nib along­side im­mune-check­point in­hi­bi­tion has al­ready shown promise in an ear­ly phase 1 clin­i­cal tri­al. We look for­ward to fur­ther ex­am­in­ing this po­ten­tial with cabozan­ti­nib plus ate­zolizum­ab to treat a range of gen­i­touri­nary and oth­er tu­mors.”

At the In­flec­tion Point for the Next Gen­er­a­tion of Can­cer Im­munother­a­py

While oncology researchers have long pursued the potential of cellular immunotherapies for the treatment of cancer, it was unclear whether these therapies would ever reach patients due to the complexity of manufacturing and costs of development. Fortunately, the recent successful development and regulatory approval of chimeric antigen receptor-engineered T (CAR-T) cells have demonstrated the significant benefit of these therapies to patients.

Stéphane Bancel, Moderna CEO

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Even as public health officials remain guarded about their comments on the likelihood Omicron will escape the reach of the currently approved Covid-19 vaccines, there’s growing scientific consensus that we’re facing a variant that threatens to overwhelm the vaccine barricades that have been erected.

Stéphane Bancel, the CEO of Moderna, one of the leading mRNA players whose quick vault into the markets with a highly effective vaccine created an instant multibillion-dollar market, added his voice to the rising chorus early Tuesday. According to Bancel, there will be a significant drop in efficacy when the average immune system is confronted by Omicron. The only question now is: How much?

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Philip Dormitzer

Glax­o­SmithK­line poach­es Pfiz­er's vi­ral vac­cines lead in rush to cap­i­tal­ize on fu­ture of mR­NA

GlaxoSmithKline has appointed Philip Dormitzer, formerly chief scientific officer of Pfizer’s viral vaccines unit, as its newest global head of vaccines R&D, looking to leverage one of the leading minds behind Pfizer and BioNTech’s RNA collaboration that led to Covid-19 jab Comirnaty, the British drug giant said Tuesday.

Dormitzer had been with Pfizer for a little more than six years, joining up after a seven-year stint with Novartis, where he reached the role of US head of research and head of global virology for the company’s vaccines and diagnostics unit.

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In­tro­duc­ing End­points Stu­dio, a new way to ad­ver­tise with End­points-craft­ed brand­ing cam­paigns

Since our start in 2016, Endpoints has grown fast while executing our mission to cover biopharma’s most critical developments for industry pros worldwide. As readership has grown, our advertising business has too. Endpoints advertising partners support the mission and engage their desired audiences through announcements on our email and web platforms, brand recognition in our event coverage and sponsorships of Endpoints daily and weekly reports.

As lead drug runs in­to a wall, De­ci­phera slims down its pipeline, puts 140 jobs on the chop­ping block

Barely a month after disappointing data shattered hopes for a major label expansion for the GI tumor drug Qinlock, Deciphera is making a major pivot — scrapping development plans for that drug and discarding another while it hunkers down and focuses on two remaining drugs in the pipeline.

As a result, 140 of its staffers will be laid off.

The restructuring, which claims the equivalent of 35% of its total workforce, will take place across all departments including commercial, R&D as well as general and administrative support functions, Deciphera said, as it looks to streamline Qinlock-related commercial operations in the US while concentrating only on a “select number of key European markets.”

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How to use reg­istry da­ta to sup­port FDA de­ci­sion mak­ing: Agency ex­plains in new guid­ance

Drugmakers looking to design a new registry or use an existing one to support a regulatory decision on a drug’s effectiveness or safety will need to consult with a new draft guidance released Monday by the FDA.

The agency’s reliance on registry data for regulatory decisions dates back more than two decades, at least, as in 1998 Bayer won approval for its anticoagulant Refludan (withdrawn from the market in 2013 for commercial reasons) based in part on a historical control group pulled from a registry.

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Till­man Gern­gross on Omi­cron: 'It is a grim sit­u­a­tion...we’re go­ing to see a sig­nif­i­cant drop in vac­cine ef­fi­ca­cy'

Tillman Gerngross, the rarely shy Dartmouth professor, biotech entrepreneur and antibody expert, has been warning for over a year that the virus behind Covid-19 would likely continue to mutate, potentially in ways that avoid immunity from infection and the best defenses scientists developed. He spun out a company, Adagio, to build a universal antibody, one that could snuff out any potential mutation.

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In­cor­po­rat­ing Ex­ter­nal Da­ta in­to Clin­i­cal Tri­als: Com­par­ing Dig­i­tal Twins to Ex­ter­nal Con­trol Arms

Most drug development professionals are familiar with the nerve-racking wait for the read-out of a large trial. If it’s negative, is the investigational therapy ineffective? Or could the failure result from an unforeseen flaw in the design or execution of the protocol, rather than a lack of efficacy? The team could spend weeks analyzing data, but a definitive answer may be elusive due to insufficient power for such analyses in the already completed trial. These problems are only made worse if the trial had lower enrollment, or higher dropout than expected due to an unanticipated event like COVID-19. And if a trial is negative, the next one is likely to be larger and more costly — if it happens at all.

Mar­ket­ingRx roundup: Ab­b­Vie’s Hu­mi­ra TV turns fo­cus to HS skin con­di­tion; Sanofi amps par­ent­ing pol­i­cy

After years as the top spending pharma TV advertiser, AbbVie’s Humira brand finally downshifted earlier this year, ceding much of its marketing budget to up-and-coming sibling meds Skyrizi and Rinvoq. However, now Humira is back on TV with ads for another condition — Hidradenitis suppurativa (HS).

The chronic and painful skin condition results in lumps and abscesses caused by inflammation or infection of sweat glands, most often in the armpits or groin. Humira was first approved to treat HS in 2015 and remains the only FDA-approved drug for the condition. Two TV ads both note more than 30,000 people with HS have been prescribed Humira.