Peginesatide for anemia in patients with chronic kidney disease not receiving dialysis.

Peginesatide for anemia in patients with chronic kidney disease not receiving dialysis.

MedLine Citation:	PMID: 23343062 Owner: NLM Status: MEDLINE
Abstract/OtherAbstract:	BACKGROUND: Peginesatide is a peptide-based erythropoiesis-stimulating agent (ESA) that may have therapeutic potential for anemia in patients with advanced chronic kidney disease. We evaluated the safety and efficacy of peginesatide, as compared with another ESA, darbepoetin, in 983 such patients who were not undergoing dialysis. METHODS: In two randomized, controlled, open-label studies (PEARL 1 and 2), patients received peginesatide once a month, at a starting dose of 0.025 mg or 0.04 mg per kilogram of body weight, or darbepoetin once every 2 weeks, at a starting dose of 0.75 μg per kilogram. Doses of both drugs were adjusted to achieve and maintain hemoglobin levels between 11.0 and 12.0 g per deciliter for 52 weeks or more. The primary efficacy end point was the mean change from the baseline hemoglobin level to the mean level during the evaluation period; noninferiority was established if the lower limit of the two-sided 97.5% confidence interval was -1.0 g per deciliter or higher. Cardiovascular safety was evaluated on the basis of an adjudicated composite end point. RESULTS: In both studies and at both starting doses, peginesatide was noninferior to darbepoetin in increasing and maintaining hemoglobin levels. The mean differences in the hemoglobin level with peginesatide as compared with darbepoetin in PEARL 1 were 0.03 g per deciliter (97.5% confidence interval [CI], -0.19 to 0.26) for the lower starting dose of peginesatide and 0.26 g per deciliter (97.5% CI, 0.04 to 0.48) for the higher starting dose, and in PEARL 2 they were 0.14 g per deciliter (97.5% CI, -0.09 to 0.36) and 0.31 g per deciliter (97.5% CI, 0.08 to 0.54), respectively. The hazard ratio for the cardiovascular safety end point was 1.32 (95% CI, 0.97 to 1.81) for peginesatide relative to darbepoetin, with higher incidences of death, unstable angina, and arrhythmia with peginesatide. CONCLUSIONS: The efficacy of peginesatide (administered monthly) was similar to that of darbepoetin (administered every 2 weeks) in increasing and maintaining hemoglobin levels. However, cardiovascular events and mortality were increased with peginesatide in patients with chronic kidney disease who were not undergoing dialysis. (Funded by Affymax and Takeda Pharmaceutical; ClinicalTrials.gov numbers, NCT00598273 [PEARL 1], NCT00598442 [PEARL 2], NCT00597753 [EMERALD 1], and NCT00597584 [EMERALD 2].).

Authors:	Iain C Macdougall; Robert Provenzano; Amit Sharma; Bruce S Spinowitz; Rebecca J Schmidt; Pablo E Pergola; Raja I Zabaneh; Sandra Tong-Starksen; Martha R Mayo; Hong Tang; Krishna R Polu; Anne-Marie Duliege; Steven Fishbane;
Publication Detail:	Type: Clinical Trial, Phase III; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
Journal Detail:	Title: The New England journal of medicine Volume: 368 ISSN: 1533-4406 ISO Abbreviation: N. Engl. J. Med. Publication Date: 2013 Jan
Date Detail:	Created Date: 2013-01-24 Completed Date: 2013-02-01 Revised Date: 2013-04-18
Medline Journal Info:	Nlm Unique ID: 0255562 Medline TA: N Engl J Med Country: United States
Other Details:	Languages: eng Pagination: 320-32 Citation Subset: AIM; IM
Affiliation:	Renal Unit, King's College Hospital, London, United Kingdom. iain.macdougall@nhs.net
Data Bank Information
Bank Name/Acc. No.:	ClinicalTrials.gov/NCT00597584; NCT00597753; NCT00598273; NCT00598442
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MeSH Terms
Descriptor/Qualifier:	Aged Anemia / drug therapy, etiology Antibodies / blood Cardiovascular Diseases / etiology Disease-Free Survival Drug Administration Schedule Erythropoietin / adverse effects, analogs & derivatives, therapeutic use Female Hematinics / adverse effects, therapeutic use* Hemoglobins / analysis Humans Kaplan-Meier Estimate Male Middle Aged Peptides / adverse effects, immunology, therapeutic use* Renal Insufficiency, Chronic / blood, complications, mortality, therapy*
Chemical
Reg. No./Substance:	0/Antibodies; 0/Hematinics; 0/Hemoglobins; 0/Peptides; 0/peginesatide; 11096-26-7/Erythropoietin; 209810-58-2/darbepoetin alfa
Investigator
Investigator/Affiliation:	Steven Fishbane / ; Pablo E Pergola / ; Diogo S Belo / ; Raja I Zabaneh / ; Chao H Sun / ; John H Durham / ; A Kaldun Nossuli / ; James K Saiki / ; Riad Darwish / ; Jose L Cangiano / ; Venu M Kondle / ; Richard A Cottiero / ; Paul W Crawford / ; Joey O Buquing / ; Mohammad Ismail / ; Jack W Moncrief / ; Marializa V Bernardo / ; Matthew Esson / ; Susan V Yue / ; Steven Fishbane / ; Jeffrey D Horowitz / ; Christopher Chien D Mai / ; Larry Froch / ; Rekha D Halligan / ; Andrew Levine / ; Dennis L Ross / ; Elizabeth A Barranco Santana / ; Jesus Navarro / ; Izuchukwu E Nwakoby / ; Baudouin Leclercq / ; Luis J Quesada / ; Mohamed Sekkarie / ; Vijay Bhasin / ; Uday Desai / ; Eugenia M Galindo-Ramos / ; Nelson P Kopyt / ; Susie Q Lew / ; Raffi R Minasian / ; G Edward Newman / ; Purushottam M Reddy / ; Chris Sholer / ; Henry J Simon / ; Thomas B Wiegmann / ; Azazuddin A Ahmed / ; David L Blecker / ; Howard M Karp / ; Azzour Hazzan / ; Akhtar Ashfaq / ; Joachim Hertel / ; Aamir Jamal / ; Shawkat N Shafik / ; Cesar Albarracin / ; Akram Al-Makki / ; Robert M Black / ; Richard P Flick / ; Mark R Kaplan / ; Csaba Kovesdy / ; Rafael A Lopez / ; John E Reed / ; Michael H Walczyk / ; Mark Fredrick / ; George Frem / ; Adeel Khan / ; Richard Lafayette / ; David Leehey / ; Samuel O Mayeda / ; Nicholas Brian Monaco / ; Mohammad A Quasem / ; Jared Sugihara / ; Edmund Tse / ; John K Endsley / ; John Fassler / ; Stuart Steven Haigler / ; Henry Cremisi / ; James A Tumlin / ; Claudia Hura / ; Mark Lee / ; Edgardo L Pellegrini / ; Robert Provenzano / ; Iain C Macdougall / ; Edouard R Martin / ; Carmen Ortiz-Butcher / ; Mohamed El-Shahawy / ; George Z Fadda / ; Bruce S Spinowitz / ; Bhasker Rai Mehta / ; Amit Sharma / ; Steven Zeig / ; Edgardo Laurel / ; Mark Alan Richter / ; Joseph Aiello / ; Ahmed A Arif / ; Dinesh Bhatia / ; Kamal V Gandhi / ; Robert Provenzano / ; Rebecca J Schmidt / ; Mario O Belledonne / ; Ranjit Cheriyan / ; John M Gilbert / ; Paul D Schneider / ; Anita Patel / ; Arnold Silva / ; Anil K Agarwal / ; Ajay Gupta / ; Avin D Rekhi / ; Michael Roppolo / ; Kenneth B Smith / ; Samir N Tuma / ; Cosme Cruz / ; Gary H Shaw / ; Jacob Alexander / ; Paolo Fanti / ; Michael Germain / ; Jeffrey K Kingsley / ; David William Koeper / ; Akin O Ogundipe / ; Francis M Vazquez Roura / ; Richard Solomon / ; Akshey Gupta / ; Theodore S Herman / ; Rallabhandi Sankaram / ; Jerry A Dancik / ; Robert V Pinnick / ; Uwe Kraatz / ; Gabriel Bako / ; Daniela Valentinova Monova / ; Eva Peterfai / ; Iain C Macdougall / ; Margarita Velkova Velkova / ; Tamas Szabo / ; Francesco Locatelli / ; Igor Macel / ; Michal C Mysliwiec / ; Angelina Lyubomirova Angelova / ; Adrian Covic / ; Regina Jack Djerassi / ; Giuseppe Villa / ; Andrzej Wiecek / ; Krzysztof Marczewski / ; Boleslaw Rutkowski / ; Csaba Salamon / ; Silvia Velciov / ; Robert Nicholas Foley / ; Jeffery S Berns / ; Brent Alan Blumenstein / ; Ravi I Thadhani / ; Michael H Humphreys / ; Joseph L Blackshear / ; Jonathan G Howlett / ; Frederick A Masoudi / ; Andrew D Michaels / ; Robert E Safford / ; David J Whellan / ; Kyra J Becker / ; Robert Hart / ; Dawn McGuire /
Comments/Corrections
Comment In:	N Engl J Med. 2013 Jan 24;368(4):387-9 [PMID: 23343068 ] N Engl J Med. 2013 Apr 18;368(16):1553 [PMID: 23594011 ] N Engl J Med. 2013 Apr 18;368(16):1553-4 [PMID: 23594010 ]

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