An­oth­er one bites the dust: Bris­tol My­ers Squibb pulls 'dan­gling' ac­cel­er­at­ed ap­proval for Op­di­vo in liv­er can­cer

Bris­tol My­ers Squibb has agreed to pull a sec­ond-line liv­er can­cer in­di­ca­tion for its block­buster Op­di­vo as a monother­a­py, be­com­ing the sec­ond PD-(L)1 in­di­ca­tion to bite the dust af­ter the FDA’s on­col­o­gy ad­comm re­viewed six “dan­gling” ac­cel­er­at­ed ap­provals in April.

The out­side ex­perts vot­ed against two of the six in­di­ca­tions dis­cussed at the meet­ing, in­clud­ing Op­di­vo as a monother­a­py for he­pa­to­cel­lu­lar car­ci­no­ma (HCC) pa­tients who have pre­vi­ous­ly been treat­ed with so­rafenib, and Mer­ck’s Keytru­da as a third-line treat­ment for stom­ach can­cer. The ad­comm vot­ed 5 to 4 not to main­tain Op­di­vo’s in­di­ca­tion, af­ter it failed to show clin­i­cal ben­e­fit in a con­fir­ma­to­ry tri­al.

Jonathan Cheng

“We are dis­ap­point­ed by the po­si­tion the Ad­vi­so­ry Com­mit­tee and the FDA have tak­en re­gard­ing the con­tin­ued ap­proval of Op­di­vo monother­a­py as a treat­ment for HCC post-so­rafenib,” BMS’ SVP and head of on­col­o­gy de­vel­op­ment Jonathan Cheng said in a state­ment.

“For the past three and a half years, Op­di­vo monother­a­py has been an im­por­tant op­tion that physi­cians have re­lied on to ad­dress this need and is cur­rent­ly the most com­mon­ly used ther­a­py in the post-so­rafenib set­ting,” he added.

Mer­ck pulled Keytru­da’s stom­ach can­cer in­di­ca­tion at the be­gin­ning of this month, not­ing: “we re­spect the FDA’s ef­forts to con­tin­u­al­ly eval­u­ate ac­cel­er­at­ed ap­provals.”

Op­di­vo won an ac­cel­er­at­ed ap­proval as a sec­ond-line treat­ment for HCC back in 2017, be­com­ing the first im­munother­a­py to get OK’d for this in­di­ca­tion. Two years lat­er, a con­fir­ma­to­ry study didn’t meet sta­tis­ti­cal sig­nif­i­cance in its pri­ma­ry end­point of over­all sur­vival. Last March, the drug land­ed an­oth­er, sep­a­rate ac­cel­er­at­ed ap­proval in com­bi­na­tion with Yer­voy for the same set­ting.

SVB Leerink se­nior re­search an­a­lyst Daina Gray­bosch pre­dict­ed back in April the mar­ket im­pact from the two with­drawals would be “in­con­se­quen­tial,” as there’s a “small and shrink­ing num­ber of pa­tients el­i­gi­ble” for Keytru­da as a third-line gas­tric can­cer treat­ment, and Bris­tol My­ers could shift HCC pa­tients to its Op­di­vo plus Yer­voy com­bi­na­tion.

But Thomas Abrams, an as­so­ci­at­ed pro­fes­sor at Har­vard Med­ical School and paid Mer­ck con­sul­tant, said dur­ing the ad­comm that the com­bo treat­ment is re­served for fit­ter pa­tients who failed a ty­ro­sine ki­nase in­hibitor (TKI) in the first line. Pa­tients on the monother­a­py have more co­mor­bidi­ties, he said, adding that “they re­al­ly are two dif­fer­ent pa­tient pop­u­la­tions.”

When Richard Paz­dur, di­rec­tor of the FDA’s On­col­o­gy Cen­ter of Ex­cel­lence, pressed Bris­tol My­ers da­ta for the re­sponse rate in this pop­u­la­tion, though, the drug­mak­er came up short.

“You’re ad­vo­cat­ing for a new in­di­ca­tion, please pro­vide the re­sponse rate – not anec­do­tal in­for­ma­tion,” Paz­dur said.

While Bris­tol My­ers says it has ad­di­tion­al tri­als in the works for the use of Op­di­vo as a monother­a­py and in com­bi­na­tion with Yer­voy “across dif­fer­ent dis­ease set­tings,” the com­pa­ny said on Fri­day that it’s al­so pur­su­ing “new ther­a­peu­tic ap­proach­es” for pa­tients with HCC.

What Will it Take to Re­al­ize the Promise and Po­ten­tial of Im­mune Cell Ther­a­pies?

What does it take to get to the finish line with a new cancer therapy – fast? With approvals in place and hundreds of immune cell therapy candidates in the pipeline, the global industry is poised to create a fundamental shift in cancer treatments towards precision medicine. At the same time, unique challenges associated with cell and process complexity present manufacturing bottlenecks that delay speed to market and heighten cost of goods sold (COGS) — these hurdles must be overcome to make precision treatments an option for every cancer patient. This series of articles highlights some of the key manufacturing challenges associated with the production of cell-based cancer therapies as well as the solutions needed to transcend them. Automation, process knowledge, scalability, and assured supply of high-quality starting material and reagents are all critical to realizing the full potential of CAR-based therapies and sustaining the momentum achieved in recent years. The articles will highlight leading-edge technologies that incorporate these features to integrate across workflows, accelerate timelines and reduce COGS – along with how these approaches are enabling the biopharmaceutical industry to cross the finish line faster with new treatment options for patients in need.

The biggest ques­tions fac­ing gene ther­a­py, the XLMTM com­mu­ni­ty, and Astel­las af­ter fourth pa­tient death

After three patients died last year in an Astellas gene therapy trial, the company halted the study and began figuring out how to safely get the program back on track. They would, executives eventually explained, cut the dose by more than half and institute a battery of other measures to try to prevent the same thing from happening again.

Then tragically, Astellas announced this week that the first patient to receive the new regimen had died, just weeks after administration.

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As­traZeneca touts Imfinzi im­munother­a­py com­bos for lung can­cer in push to dri­ve PD-L1 drug up­take

Facing the big dogs in the PD-(L)1 space, AstraZeneca has taken its own contender Imfinzi into blockbuster territory in its four years on the market but sees even bigger things for the drug. Combinations could be the key, and early results from a mid-stage test are adding some fuel to that strategy.

Imfinzi combined with one of two investigational immunotherapies — a CD73 antibody dubbed oleclumab or an anti-NGK2a named monalizumab — topped Imfinzi alone in terms of overall response and progression-free survival in patients with stage III non-small cell lung cancer whose tumors had not worsened during concurrent chemoradiation, according to interim data from the Phase II COAST trial set to be presented at #ESMO21.

Amgen VP of R&D David Reese

Am­gen rolls out da­ta for KRAS in­hibitor com­bo study in col­orec­tal can­cer, hop­ing to move on from ug­ly ear­ly re­sults

With the first win for its KRAS inhibitor sotorasib in hand, Amgen is pushing ahead with an aggressive clinical plan to capitalize on its first-to-market standing. The drugmaker thinks combinations — in-house or otherwise — could offer a path forward, and one early readout from that strategy is bearing fruit.

A combination of Amgen’s sotorasib and its EGFR inhibitor Vectibix posted an overall response rate of 27% in 26 patients with advanced colorectal cancer (CRC) with the KRAS-G12C mutation, according to data from the larger Phase Ib/II CODEBREAK 101 study set to present at this weekend’s virtual ESMO Congress.

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Dan O'Day, Gilead CEO (Jim Watson/AFP via Getty Images)

Eu­ro­pean study finds that Gilead­'s Covid-19 an­tivi­ral remde­sivir shows no clin­i­cal ben­e­fit

Gilead’s remdesivir — or Veklury, as it’s marketed in the US — raked in around $2.8 billion last year as the only FDA-approved antiviral to treat Covid-19. But new data from a European study suggest the drug, which has been given to about half of hospitalized Covid patients in the country, has no actual benefit.

The open-label DisCoVeRy trial enrolled Covid-19 patients across 48 sites in Europe to test a handful of treatments, including remdesivir, lopinavir–ritonavir, lopinavir–ritonavir and interferon beta-1a, and hydroxychloroquine. To participate, patients had to show symptoms for seven days and require oxygen support. A total of 429 patients were randomized to receive remdesivir plus standard of care, while 428 were assigned to standard of care alone.

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Gri­fols drops $1B on Ger­man hold­ing com­pa­ny in con­tin­ued plas­ma push

One Spanish biotech is beefing up its plasma therapy operations, and on Friday, it announced that it’s doing so in a billion-dollar deal.

Grifols is now the largest shareholder of Biotest, a company valued at more than $1.8 billion. By teaming up, the two will try to increase the number of plasma therapies available and increase patient access around the world, Grifols said in a press release.

The company did so by acquiring holding company Tiancheng Pharmaceutical, the Germany-based owner of nearly 90% of Biotest shares, for nearly $1.27 billion. Grifols now owns nearly 90% of Biotest voting rights and almost 45% of the total share capital of Biotest.

Covid-19 roundup: FDA re­veals boost­er ad­comm ques­tion; Eli Lil­ly's an­ti­body cock­tail cleared for pre­ven­tion

The FDA released briefing documents this week from the agency and Pfizer each outlining their arguments for today’s Covid-19 booster shot adcomm, but one thing conspicuously missing was the question on which panel members would be voting. But late Thursday night, regulators published that question.

Adcomm members will be asked whether or not the safety and efficacy data from Pfizer/BioNTech’s original Phase III study “support approval” of a booster shot at least six months after the second dose in individuals older than 16. The question notably excludes the real-world data from Israel and other analyses that Pfizer and the Biden administration had said would be a centerpiece of their arguments for boosters.

A Pfiz­er part­ner wel­comes ex-ADC Ther­a­peu­tics CMO Jay Fein­gold to the team; Amid tough sled­ding, Im­muno­vant choos­es Eli Lil­ly alum as CFO

→ Last week we told you about the CMO revolving door at ADC Therapeutics, as Joseph Camardo replaced the departing Jay Feingold. The next opportunity for Feingold in the CMO slot has opened up at antibody-drug conjugate and mAb developer Pyxis Oncology, which has added several new execs and scientific advisory board members in recent months, including ex-Immunovant CFO Pamela Yanchik Connealy. Before his tenure at ADC, Feingold was Daiichi Sankyo’s VP of US medical affairs and chairman of the Global Medical Affairs Oversight Committee. Within weeks in March, Pyxis struck a licensing deal with Pfizer for two of its ADCs and raked in $152 million from a Series B round.

Take­da scores a win for a rare type of lung can­cer, gear­ing up for a show­down with J&J

Four months after J&J’s infused drug Rybrevant scored the industry’s first win in a rare type of non-small cell lung cancer (NSCLC), Takeda is following up with an oral option for the small but desperate patient population.

The FDA granted an accelerated approval to Takeda’s oral TKI inhibitor Exkivity (mobocertinib) in metastatic NSCLC patients with EGFR exon 20 gene mutations who had previously undergone platinum-based chemotherapy, the company announced on Wednesday.

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