Skip to content
Bending the Curve Trial by Trial
?

Microtubule-targeting agentsIn useDerivative of an earlier drug

Eribulin

Also known as Halaven, eribulin mesylate, E7389, ER-086526

A synthetic analogue of halichondrin B, a compound from a marine sponge, given by injection. Its US label lists metastatic breast cancer after at least two chemotherapy regimens and unresectable or metastatic liposarcoma after an anthracycline.

From discovery to approval

  1. 2001 · Earliest report found

    Halichondrin B was originally isolated from the Japanese marine sponge Halichondria okadai, according to a 2015 review that dates this to 1985. Simplified synthetic analogues, including ER-086526 (later named eribulin), were reported in 2001, the earliest paper found; no source read dates eribulin's first synthesis.[2][3][4][5][6][7][8][1][9]

  2. 2002 · First use in people

    A 2015 review says eribulin was presented to the National Cancer Institute's Drug Development Group in 1998 and entered phase I clinical trials in 2002.[2]

  3. 2010-11-15 · FDA regular

    Metastatic breast cancer in patients who have previously received at least two chemotherapeutic regimens for metastatic disease, with prior therapy that should have included an anthracycline and a taxane in the adjuvant or metastatic setting (NDA 201532). The source is a replacement letter that corrects a postmarketing timetable; the effective action date remains 15 November 2010. The type regular is an inference: no accelerated-approval wording was found.[9]

  4. 2011-03-17 · EMA regular

    Marketing authorisation issued 17 March 2011 (EMEA/H/C/002084). The EPAR page lists current indications in locally advanced or metastatic breast cancer after at least one chemotherapy regimen for advanced disease, and in unresectable liposarcoma after anthracycline-containing therapy; the original 2011 wording is not given there. The page does not mention a conditional or exceptional-circumstances authorisation; the type regular is an inference from that absence.[10]

  5. 2016-01-28 · FDA regular

    Unresectable or metastatic liposarcoma in patients who have received a prior anthracycline-containing regimen (NDA 201532/S-015); narrower than the trial population, which included leiomyosarcoma. The letter contains no accelerated-approval wording; the type 'regular' is an inference.[11]

How it works

The label says eribulin inhibits the growth phase of microtubules without affecting the shortening phase, and sequesters tubulin into nonproductive aggregates. This leads to a G2/M block, disrupted mitotic spindles and, after prolonged mitotic blockage, apoptosis.[1]

Where it came from and why

Halichondrin B was potent, but the sponges could not supply enough of it. A 2001 paper says a complete synthetic route allowed structurally simpler analogues that kept the potency of the natural product.

Halichondrin B is a large polyether macrolide that Swami and colleagues say was originally isolated in 1985 from a rare Japanese marine sponge, Halichondria okadai [2]. When the National Cancer Institute's 60-cell-line screening data were probed with known antimitotic agents, halichondrin B and homohalichondrin B appeared repeatedly, which led to the finding of a tubulin-based mechanism [3]. Development stalled because the sponges could not supply enough of the compound [2] [6].

A total synthesis of halichondrin B and norhalichondrin B was reported in 1992 by a group that included Yoshito Kishi [5], although Swami and colleagues date his completely synthetic method to 1998 [2]. With a synthetic route available, structurally simpler macrocyclic ketone analogues were made; a 2001 paper reported two of them, ER-076349 and ER-086526, with growth inhibition at sub-nanomolar concentrations in cell lines [6]. Swami and colleagues give ER-086526 as an earlier code name of eribulin, also called E7389 [2].

The same review says eribulin was presented to the National Cancer Institute's Drug Development Group in 1998 and entered phase I trials in 2002 [2]. The FDA approved it on 15 November 2010 [9].

Cancers

  • Metastatic breast cancer

    The US label lists treatment of metastatic breast cancer in patients who have previously received at least two chemotherapeutic regimens for metastatic disease, with prior therapy that should have included an anthracycline and a taxane.[1]

  • Liposarcoma

    The label lists unresectable or metastatic liposarcoma in patients who have received a prior anthracycline-containing regimen.[1]

  • Liposarcoma and leiomyosarcoma (phase III)

    A randomised phase III trial compared eribulin with dacarbazine in patients with advanced liposarcoma or leiomyosarcoma who had received at least two previous systemic regimens including an anthracycline; the primary endpoint was overall survival.[12]

Worth knowing

  • Halichondrin B was shown not to interfere with colchicine binding to tubulin but to inhibit the binding of vinblastine noncompetitively, which placed it in the vinca domain of tubulin; the 1991 study reached this by analysing differential cytotoxicity data from the NCI cell-line screen.[3]
  • The label describes eribulin mesylate as a synthetic analogue of halichondrin B, a product isolated from the marine sponge Halichondria okadai.[1]
  • A summary of the EMA's review says that in the pivotal breast cancer trial median overall survival was 13.2 months with eribulin against 10.6 months in the control arm (hazard ratio 0.805, 95% CI 0.677 to 0.958; P = 0.014).[13]
  • In the 2001 study, two synthetic macrocyclic ketone analogues showed in vivo activity at 0.1 to 1 mg/kg against four human tumour xenografts: breast, colon, melanoma and ovarian.[6]

On this site

References

  1. Eisai Inc.. Halaven (eribulin mesylate) injection: prescribing information. DailyMed, set ID 31ce4750-ded5-4a0b-95e9-f229fa6bc822, published 17 November 2025. Source
  2. Swami U, Shah U, Goel S. Eribulin in Cancer Treatment. Mar Drugs. 2015;13(8):5016-58. PubMedDOI
  3. Bai RL, Paull KD, Herald CL, Malspeis L, Pettit GR, Hamel E. Halichondrin B and homohalichondrin B, marine natural products binding in the vinca domain of tubulin. Discovery of tubulin-based mechanism of action by analysis of differential cytotoxicity data. J Biol Chem. 1991;266(24):15882-9. PubMed
  4. Hirata Y, Uemura D. Halichondrins - antitumor polyether macrolides from a marine sponge. Pure and Applied Chemistry. 1986;58(5):701-710. DOI
  5. Aicher TD, Buszek KR, Fang FG, Forsyth CJ, Jung SH, Kishi Y, et al. Total synthesis of halichondrin B and norhalichondrin B. Journal of the American Chemical Society. 1992;114(8):3162-3164. DOI
  6. Towle MJ, Salvato KA, Budrow J, Wels BF, Kuznetsov G, Aalfs KK, et al. In vitro and in vivo anticancer activities of synthetic macrocyclic ketone analogues of halichondrin B. Cancer Res. 2001;61(3):1013-21. PubMed
  7. Zheng W, Seletsky BM, Palme MH, Lydon PJ, Singer LA, Chase CE, et al. Macrocyclic ketone analogues of halichondrin B. Bioorg Med Chem Lett. 2004;14(22):5551-4. PubMedDOI
  8. Jimeno A. Eribulin: rediscovering tubulin as an anticancer target. Clin Cancer Res. 2009;15(12):3903-5. PubMedDOI
  9. U.S. Food and Drug Administration. Replacement NDA approval letter, Halaven (eribulin mesylate) injection, NDA 201532, Eisai, Incorporated; effective action date 15 November 2010, electronic signature dated 11/15/2010. Source
  10. European Medicines Agency. Halaven (eribulin): EPAR product page (EMEA/H/C/002084); page shows last update 11 October 2024. Read 2026-10-29. Source
  11. US Food and Drug Administration. Supplement approval letter, NDA 201532/S-015 (Halaven, eribulin mesylate), Eisai Inc. Appended electronic signature page dated 28 January 2016. Source
  12. Schöffski P, Chawla S, Maki RG, Italiano A, Gelderblom H, Choy E, et al. Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet. 2016;387(10028):1629-37. PubMedDOI
  13. Pean E, Klaar S, Berglund EG, Salmonson T, Borregaard J, Hofland KF, et al. The European medicines agency review of eribulin for the treatment of patients with locally advanced or metastatic breast cancer: summary of the scientific assessment of the committee for medicinal products for human use. Clin Cancer Res. 2012;18(17):4491-7. PubMedDOI