Tib­so­vo clears an­oth­er hur­dle for Servi­er, but can it make Agios' old drug prof­itable?

When Eu­ro­pean reg­u­la­tors saw the da­ta Agios used to win US ap­proval for their AML drug Tib­so­vo, they sent the more than decade-old biotech back to the draw­ing board. A sin­gle, sin­gle-armed tri­al was not go­ing to cut it.

On Mon­day, though, the drug’s new own­ers an­nounced it had cleared a more rig­or­ous study. In a ran­dom­ized, Phase III tri­al of cer­tain new­ly di­ag­nosed pa­tients, those who re­ceived a com­bi­na­tion of Tib­so­vo and chemother­a­py lived longer than those who re­ceived a com­bi­na­tion of place­bo and chemother­a­py. Those pa­tients al­so had high­er re­sponse rates and com­plete re­mis­sion rates.

The re­sults ac­tu­al­ly sur­passed the goal­posts Agios ex­ec­u­tives had set when they de­signed the tri­al in 2017. Al­though over­all sur­vival was a sec­ondary end­point, the pri­ma­ry end­point was sim­ply event-free sur­vival: the time un­til a treat­ment fail­ure, re­lapse, or death. The tri­al hit that end­point too.

The re­sults are a win for the 8% of AML pa­tients with an IDH1 mu­ta­tion — the sub­set el­i­gi­ble for Tib­so­vo, a tar­get­ed ther­a­py — who con­tin­ue to face a grim prog­no­sis and few op­tions out­side of chemo. They of­fer the first ev­i­dence that Tib­so­vo can not on­ly work by it­self but al­so in com­bi­na­tion with chemother­a­py.

The da­ta are al­so a boon for Servi­er, the French phar­ma that spent near­ly $2 bil­lion last year to ac­quire Tib­so­vo and the rest of Agios’ can­cer pipeline. In part be­cause so few pa­tients have AML with IDH1 mu­ta­tion, the biotech had strug­gled to turn its sci­en­tif­ic suc­cess in­to a com­mer­cial suc­cess, col­lect­ing on­ly about $30 mil­lion per quar­ter from the drug be­fore the sale.

Servi­er was bet­ting both that the ex­per­i­men­tal mol­e­cules Agios was putting through tri­als held promise and that its own ex­ten­sive com­mer­cial ex­pe­ri­ence would al­low them to boost Tib­so­vo bet­ter than the small­er biotech could. The new re­sults should al­low the com­pa­ny to mar­ket the drug more wide­ly in the US and al­low the French phar­ma to file again for ap­proval in Eu­rope.

Servi­er did not break down de­tailed re­sults from the study but said it would do so at a fu­ture med­ical con­fer­ence. If the com­pa­ny us­es the da­ta to get ap­proval in Eu­rope, it would like­ly be in a slight­ly dif­fer­ent in­di­ca­tion than they had orig­i­nal­ly ap­plied for: new­ly di­ag­nosed AML pa­tients with an IDH1 mu­ta­tion, rather than IDH1-pos­i­tive AML pa­tients who have al­ready re­ceived treat­ments.

Tib­so­vo, though, may not be alone on the mar­ket for long. For­ma Ther­a­peu­tics re­leased da­ta last year from their own tar­get­ed IDH1-pos­i­tive AML treat­ment that looked re­mark­ably sim­i­lar to the da­ta Agios used to gain ap­proval. A For­ma ap­proval would give pa­tients a sec­ond op­tion but, for Servi­er, put an­oth­er ob­sta­cle to mak­ing Tib­so­vo prof­itable.

“Tib­so­vo monother­a­py has been in­stru­men­tal in trans­form­ing out­comes for adult pa­tients with new­ly di­ag­nosed or re­lapsed re­frac­to­ry AML har­bor­ing an IDH1 mu­ta­tion,” Servi­er VP of clin­i­cal de­vel­op­ment Su­san Pandya said in a state­ment. “These promis­ing re­sults from the AG­ILE study sup­port the added ben­e­fit of in­hibit­ing the mu­tant IDH1 en­zyme in com­bi­na­tion with stan­dard chemother­a­py in the new­ly di­ag­nosed in­ten­sive chemother­a­py in­el­i­gi­ble set­ting.”

So­cial: HJBC / Shut­ter­stock

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.