Beloranib Explained

Beloranib is a former drug candidate for the treatment of obesity. It was discovered by CKD Pharmaceuticals and its clinical development was led by Zafgen.[1] Drug development was halted in 2016 after deaths during clinical trials.[2]

Mechanism of action

Beloranib, an analog of the natural chemical compound fumagillin, is an inhibitor of the enzyme METAP2.[3] It was originally designed as angiogenesis inhibitor for the treatment of cancer.[4] However, once the potential anti-obesity effects of METAP2 inhibition became apparent, the clinical development began to focus on these effects and beloranib has shown positive results in preliminary clinical trials for this indication.[5]

Clinical trials

A Phase I trial was published in 2013,[6] finding a dose that led to weight loss in obese women in comparison to placebo. Results from a Phase II clinical trial for obesity were promising with clinically meaningful weight loss and improvements in cardiometabolic risk factors in the treated group.[7] Zafgen continued with a Phase III trial for Prader–Willi syndrome.[8]

In December 2015, Zafgen halted the Phase III clinical trial of beloranib for Prader–Willi syndrome after a second patient death in order to determine whether the deaths were treatment-related.[9] After discussions with the Food and Drug Administration indicated that the obstacles to gaining approval were insurmountable, product development for beloranib was ended.[2]

Notes and References

  1. Web site: News Release: Zafgen Secures $33 Million Series C Financing . Zafgen, Inc. . July 7, 2011 . dead . https://web.archive.org/web/20111210094436/http://www.zafgen.com/PDF/zafgen-series-c-070711.pdf . December 10, 2011 .
  2. News: Zafgen Halts Development of Beloranib, to Cut Jobs by ~34% . nasdaq.com . July 20, 2016.
  3. Chun E, Han CK, Yoon JH, Sim TB, Kim YK, Lee KY . Novel inhibitors targeted to methionine aminopeptidase 2 (MetAP2) strongly inhibit the growth of cancers in xenografted nude model . International Journal of Cancer . 114 . 1 . 124–30 . March 2005 . 15523682 . 10.1002/ijc.20687 . free .
  4. Kim EJ, Shin WH . General pharmacology of CKD-732, a new anticancer agent: effects on central nervous, cardiovascular, and respiratory system . Biological & Pharmaceutical Bulletin . 28 . 2 . 217–23 . February 2005 . 15684472 . 10.1248/bpb.28.217 . free .
  5. Web site: Zafgen Announces Positive Topline Phase 1b Data for ZGN-433 in Obesity . 5 January 2011 . MedNews . Drugs.com .
  6. Hughes TE, Kim DD, Marjason J, Proietto J, Whitehead JP, Vath JE . Ascending dose-controlled trial of beloranib, a novel obesity treatment for safety, tolerability, and weight loss in obese women . Obesity . 21 . 9 . 1782–8 . September 2013 . 23512440 . 10.1002/oby.20356 . 2352854 .
  7. Kim DD, Krishnarajah J, Lillioja S, de Looze F, Marjason J, Proietto J, Shakib S, Stuckey BG, Vath JE, Hughes TE . 6 . Efficacy and safety of beloranib for weight loss in obese adults: a randomized controlled trial . Diabetes, Obesity & Metabolism . 17 . 6 . 566–572 . June 2015 . 25732625 . 10.1111/dom.12457 . 205076412 .
  8. Web site: Clinical Trials . 2014-11-18.
  9. News: UPDATE 4-Zafgen halts obesity drug trial after second patient death. Reuters . 3 December 2015 . 2015-12-03. 2015-12-03. https://web.archive.org/web/20151203084512/http://www.reuters.com/article/2015/12/03/zafgen-study-idUSL3N13R3OQ20151203. live.

This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Beloranib".

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