Perifosine Explained

Perifosine (also KRX-0401) is a former drug candidate that was under development for a variety of cancer indications. It is an alkyl-phospholipid^[1] structurally related to miltefosine. Perifosine interrupts the PI3K/AKT/mTOR pathway by acting as an allosteric AKT inhibitor targeting the pleckstrin homology domain of AKT.^[2] It was being developed by Keryx Biopharmaceuticals who had licensed it from Æterna Zentaris Inc.^[3]

In 2010, perifosine received orphan drug status in the U.S. for the treatment of multiple myeloma and neuroblastoma, and for multiple myeloma in the EU. However, both were later withdrawn.^{[4] [5]}

In 2011 it was in a phase III trial for colorectal cancer,^[6] and another for multiple myeloma.^[7] On April 2, 2012, it was announced that perifosine failed its phase III clinical trial for treatment of colon cancer.^[8] Detailed results were released in June 2012.^[9] On March 11, 2013 Aeterna Zentaris announced the discontinuing of Phase 3 clinical trial of perifosine for the treatment of relapsed and refractory multiple myeloma.^[10]

Notes and References

1. Perifosine, a novel alkylphospholipid, inhibits protein kinase B activation . Nov 2003 . Mol Cancer Ther . Kondapaka. Molecular Cancer Therapeutics . 2 . 11 . 1093–103 . 14617782 . etal.
2. 24905897. 2014. Keane. N. A.. Glavey. S. V.. Krawczyk. J.. O'Dwyer. M.. AKT as a therapeutic target in multiple myeloma. Expert Opinion on Therapeutic Targets. 18. 8. 897–915. 10.1517/14728222.2014.924507. 873910.
3. http://smartoncology.com/PDF_Issue2/Smartoncology%20February%2026%20Issue%202.pdf Smartoncology newsletter
4. Web site: FDA Orphan Drug Designations and Approvals: Perifosine.
5. Web site: EU/3/10/740: Orphan designation for the treatment of multiple myeloma: Perifosine. 17 September 2018 .
6. Web site: Perifosine Plus Capecitabine Versus Placebo Plus Capecitabine in Patients with Refractory Advanced Colorectal Cancer - Full Text View - ClinicalTrials.gov . 2011-03-24 . 2011-07-27 . https://web.archive.org/web/20110727204029/http://www.clinicaltrial.gov/ct2/show/NCT01097018 . dead .
7. News: Yakult Pays Aeterna Zentaris $8.3M for Japanese Rights to Pivotal-Stage Cancer Drug . 9 March 2011 .
8. News: Aeterna Zentaris Regains North American Rights to Akt Inhibitor from Keryx . May 2012 .
9. Web site: Aeterna Zentaris: Phase 3 Data for Perifosine in Colorectal Cancer Presented at ASCO Meeting . 4 June 2012 . 13 November 2012 . https://archive.today/20130116055911/http://www.aezsinc.com/en/page.php?p=60&q=508 . 16 January 2013 . dead .
10. Web site: Æterna Zentaris Inc . 2014-01-22 . 2014-02-02 . https://web.archive.org/web/20140202132845/http://www.aezsinc.com/en/page.php?p=60&q=550 . dead .