Skip to main content
  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

AACR logo

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Journal Sections
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Collections
      • COVID-19 & Cancer Resource Center
      • Precision Medicine and Therapeutic Resistance
      • Clinical Trials
      • Immuno-oncology
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
    • Journal Press Releases
  • COVID-19
  • Webinars
  • 10th Anniversary
  • Search More

    Advanced Search

  • AACR Publications
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Cancer Discovery
Cancer Discovery
  • Home
  • About
    • The Journal
    • AACR Journals
    • Journal Sections
    • Subscriptions
    • Permissions and Reprints
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Collections
      • COVID-19 & Cancer Resource Center
      • Precision Medicine and Therapeutic Resistance
      • Clinical Trials
      • Immuno-oncology
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
    • Journal Press Releases
  • COVID-19
  • Webinars
  • 10th Anniversary
  • Search More

    Advanced Search

News in Brief

Agios Exits Oncology

DOI: 10.1158/2159-8290.CD-NB2021-0303 Published March 2021
  • Article
  • Info & Metrics
Loading

The company behind the only two IDH-targeted drugs on the market has exited the cancer field. Late last year, Agios Pharmaceuticals, maker of the IDH1 inhibitor ivosidenib (Tibsovo) and originator of the IDH2 inhibitor enasidenib (Idhifa; Bristol Myers Squibb), announced plans to sell its oncology business to Servier for $1.8 billion plus royalties and a potential $200 million milestone payment.

Ivosidenib and enasidenib are approved to treat acute myeloid leukemia (AML). The drugs target oncogenic forms of isocitrate dehydrogenase, a key enzyme in cellular energy metabolism that, when mutated, produces a metabolite implicated in tumor progression.

The deal also includes a third IDH inhibitor, the dual IDH1/2 blocker vorasidenib (AG-881) now in phase III testing for low-grade glioma, along with two early clinical-stage assets—a MAT2A inhibitor (AG-270) and a DHODH inhibitor (AG-636)—and several preclinical discovery programs.

“We're happy that Servier wanted all of that, and was willing to pay a good price, and that they're going to invest behind them,” says Agios CEO Jacqualyn Fouse, PhD. “This was a pretty tough decision for us to take,” she adds, but it made sense given Servier's greater marketing might and pipeline of other cancer drugs ready for testing with Agios's agents.

Since the FDA approvals of ivosidenib and enasidenib in 2018 and 2017, respectively, sales of both drugs have been somewhat sluggish. The infrequency of IDH1 and IDH2 mutations, each found in roughly 10% of AML cases, partially explains the low uptake, as does direct competition with the recently approved combination of azacitidine plus the BCL2 inhibitor venetoclax (Venclexta; AbbVie/Genentech), which seems to work well in patients with IDH mutations.

Neither approval was supported by randomized, controlled trial data—and European regulators declined to approve ivosidenib based on single-arm phase I results, as the FDA had done. Plus, each IDH inhibitor carries a boxed warning about differentiation syndrome, a potentially fatal side effect.

But there are bright spots. Ivosidenib is under evaluation in two phase III studies for patients with newly diagnosed IDH1-mutant AML: In one, older patients receive the drug with azacitidine; in the other, younger patients receive a combination of ivosidenib and intensive chemotherapy. As Eytan Stein, MD, of Memorial Sloan Kettering Cancer Center in New York, NY, points out, smaller trials that he and others have run indicate that combination regimens can induce deep, durable remissions. “Down the road,” he says, “I do think we are going to be giving a backbone of azacitidine–venetoclax with [an IDH inhibitor] as a triplet.”

Potentially boosting sales further, ivosidenib could soon earn approval for previously treated IDH1-mutant cholangiocarcinoma, a biliary tract cancer. In phase III testing, patients with refractory disease who received the drug had significantly longer progression-free survival, with a trend toward longer overall survival, compared with those given placebo.

Financial models from Andrew Berens, MD, senior research analyst at SVB Leerink, put the risk-adjusted value of Agios's entire oncology portfolio at approximately $2.9 billion.

The accuracy of that forecast will ultimately depend on the fate of vorasidenib, which has shown early signs of efficacy in low-grade gliomas, around 70% to 80% of which harbor IDH mutations. A phase III, placebo-controlled trial is ongoing for patients with IDH-mutant grade 2 glioma who have been treated only with surgery.

“We are hoping that inhibition of mutant IDH will stop the otherwise relentless growth of these tumors and delay the need for radiation and chemotherapy,” says trial investigator Ingo Mellinghoff, MD, of Memorial Sloan Kettering Cancer Center.

With oncology now in the rearview mirror, Agios will focus on developing drugs that modulate cellular metabolic pathways implicated in rare genetic diseases, including thalassemia and sickle cell anemia. –Elie Dolgin

  • ©2021 American Association for Cancer Research.
PreviousNext
Back to top
Cancer Discovery: 11 (3)
March 2021
Volume 11, Issue 3
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Editorial Board (PDF)

Sign up for alerts

View this article with LENS

Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Discovery article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Agios Exits Oncology
(Your Name) has forwarded a page to you from Cancer Discovery
(Your Name) thought you would be interested in this article in Cancer Discovery.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Agios Exits Oncology
Cancer Discov March 1 2021 (11) (3) OF1; DOI: 10.1158/2159-8290.CD-NB2021-0303

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Agios Exits Oncology
Cancer Discov March 1 2021 (11) (3) OF1; DOI: 10.1158/2159-8290.CD-NB2021-0303
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Immunotherapy Activates Antitumor γ9δ2 T Cells
  • Mechanisms of KRAS Inhibitor Resistance Revealed
  • Genomic Differences by Race Emerge in Colorectal Cancer
Show more News in Brief
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook   Twitter   LinkedIn   YouTube   RSS

Articles

  • OnlineFirst
  • Current Issue
  • Past Issues

Info For

  • Authors
  • Subscribers
  • Advertisers
  • Librarians

About Cancer Discovery

  • About the Journal
  • Editors
  • Journal Sections
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2021 by the American Association for Cancer Research.

Cancer Discovery
eISSN: 2159-8290
ISSN: 2159-8274

Advertisement