Roche halts en­roll­ment in a PhII com­bo study of Tecen­triq and Cotel­lic in wake of sev­er­al pa­tient deaths

A string of deaths in a co­hort of colon can­cer pa­tients tak­ing a com­bi­na­tion of Roche’s PD-L1 check­point Tecen­triq with Ex­elix­is’ MEK in­hibitor Cotel­lic forced the in­de­pen­dent mon­i­tor­ing board to halt en­roll­ment of new pa­tients in their Phase II MOD­UL study. And Roche says one of those deaths was a treat­ment-re­lat­ed case of car­diotox­i­c­i­ty.

The study was de­signed to bring in about 1,400 pa­tients with an eye to divvy­ing them up in­to var­i­ous com­bi­na­tions with Tecen­triq for metasta­t­ic colon can­cer. Ac­cord­ing to a state­ment from Genen­tech, in­ves­ti­ga­tors opt­ed to take a proac­tive safe­ty step af­ter see­ing an im­bal­ance in pa­tient deaths in this co­hort get­ting the com­bo as a main­te­nance ther­a­py for front­line cas­es of colon can­cer, paus­ing en­roll­ment as treat­ment con­tin­ues for the pa­tients al­ready in the study.

From their state­ment:

The IDMC rec­om­men­da­tion fol­lowed an ob­served im­bal­ance in the num­ber of deaths in the ex­per­i­men­tal arm ver­sus the con­trol arm. At the time of the IDMC re­view, three deaths oc­curred on the ex­per­i­men­tal arm. One death due to car­dio­genic shock was treat­ment re­lat­ed, while the oth­er two deaths were due to dis­ease pro­gres­sion. We re­cent­ly learned of an­oth­er death in the Co­hort 4 ex­per­i­men­tal arm, which was doc­u­ment­ed as not re­lat­ed to study treat­ment. We are proac­tive­ly pro­vid­ing the lat­est in­for­ma­tion on all the cas­es to the IDMC.

That in­ter­rup­tion, though, won’t slow down IM­blaze370, a Phase III study test­ing the com­bi­na­tion for mCRC. Da­ta from that study are due out soon, rep­re­sent­ing one of the top cat­a­lysts for Roche’s big check­point cam­paign in 2018 as it tries to catch up with the lead­ers at Mer­ck and Bris­tol-My­ers Squibb. The big im­pact from the read­out, though, will lie with Ex­elix­is.

News of the sus­pen­sion in the study start­ed to spread ear­li­er this week on Twit­ter, af­ter in­ves­ti­ga­tors up­dat­ed the post­ing for this tri­al on clin­i­cal­tri­ Then Roche ac­knowl­edged the is­sue with some an­a­lysts. 

The hap­haz­ard com­mu­ni­ca­tions un­der­score the fact that there is no stan­dard ap­proach for high­light­ing safe­ty is­sues for ei­ther ex­per­i­men­tal or com­mer­cial drugs, as Roche demon­strat­ed re­cent­ly when it sent state­ments on a se­ries of 5 deaths that oc­curred among pa­tients tak­ing their big he­mo­phil­ia drug Hem­li­bra. 

Com­pa­nies take a va­ri­ety of ap­proach­es to re­port­ing the worst safe­ty cas­es in­volv­ing FDA holds, with two biotechs — Sol­id and Unum — re­cent­ly choos­ing to hold back any news on reg­u­la­to­ry ac­tions un­til they had to alert po­ten­tial in­vestors in their IPOs. It’s par­tic­u­lar­ly easy in the US, as the FDA typ­i­cal­ly keeps these tri­al-re­lat­ed events and any in­volve­ment they may have as a reg­u­la­tor un­der wraps.

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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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.

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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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.

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.