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N Engl J Med. 2013 Jan 24;368(4):320-32. doi: 10.1056/NEJMoa1203166.

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

Collaborators (156)

Fishbane S, Pergola PE, Belo DS, Zabaneh RI, Sun CH, Durham JH, Nossuli A, Saiki JK, Darwish R, Cangiano JL, Kondle VM, Cottiero RA, Crawford PW, Buquing JO, Ismail M, Moncrief JW, Bernardo MV, Esson M, Yue SV, Fishbane S, Horowitz JD, Mai CC, Froch L, Halligan RD, Levine A, Ross DL, Santana EA, Navarro J, Nwakoby IE, Leclercq B, Quesada LJ, Sekkarie M, Bhasin V, Desai U, Galindo-Ramos EM, Kopyt NP, Lew SQ, Minasian RR, Newman G, Reddy PM, Sholer C, Simon HJ, Wiegmann TB, Ahmed AA, Blecker DL, Karp HM, Hazzan A, Ashfaq A, Hertel J, Jamal A, Shafik SN, Albarracin C, Al-Makki A, Black RM, Flick RP, Kaplan MR, Kovesdy C, Lopez RA, Reed JE Jr, Walczyk MH, Fredrick M, Frem G, Khan A, Lafayette R, Leehey D, Mayeda SO, Monaco NB, Quasem MA, Sugihara J, Tse E, Endsley JK, Fassler J, Haigler SS, Cremisi H, Tumlin JA, Hura C, Lee M, Pellegrini EL, Provenzano R, Macdougall IC, Martin ER, Ortiz-Butcher C, El-Shahawy M, Fadda GZ, Spinowitz BS, Mehta BR, Sharma A, Zeig S, Laurel E, Richter MA, Aiello J, Arif AA, Bhatia D, Gandhi KV, Provenzano R, Schmidt RJ, Belledonne MO, Cheriyan R, Gilbert JM Jr, Schneider PD, Patel A, Silva A, Agarwal AK, Gupta A, Rekhi AD, Roppolo M, Smith KB, Tuma SN, Cruz C, Shaw GH, Alexander J, Fanti P, Germain M, Kingsley JK, Koeper DW, Ogundipe AO, Roura FM, Solomon R, Gupta A, Herman TS, Sankaram R, Dancik JA, Pinnick RV, Kraatz U, Bako G, Monova DV, Peterfai E, Macdougall IC, Velkova MV, Szabo T, Locatelli F, Macel I, Mysliwiec MC, Angelova AL, Covic A, Djerassi RJ, Villa G, Wiecek A, Marczewski K, Rutkowski B, Salamon C, Velciov S, Foley RN, Berns JS, Blumenstein BA, Thadhani RI, Humphreys MH, Blackshear JL, Howlett JG, Masoudi FA, Michaels AD, Safford RE, Whellan DJ, Becker KJ, Hart R, McGuire D.

Author information

  • 1Renal Unit, King's College Hospital, London, United Kingdom. iain.macdougall@nhs.net

Abstract

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].).

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PMID:
23343062
[PubMed - indexed for MEDLINE]
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