Antianemia Drug CERA Given Monthly Was Effective in Dialysis Patients

Marlene Busko

August 11, 2006

August 11, 2006 (Glasgow, Scotland) — Three large phase 3 trials found that dialysis patients were able to maintain stable hemoglobin levels when they were directly switched from frequently dosed antianemia therapy to the first continuous erythropoietin receptor activator (CERA) ( Mircera, Roche) given bimonthly or monthly.

These phase 3 "maintenance" trials were designed to demonstrate that CERA could maintain the stable hemoglobin levels attained with other therapies. The results were presented here at the 43rd European Renal Association (ERA)-European Dialysis and Transplant Association (EDTA) Congress.

The studies are part of a large phase 3 clinical development program in renal anemia, with 6 trials and 2400 patients, Nathan W. Levin, MD, from the Renal Research Institute, New York, and the lead investigator of the first study, explained to Medscape. "Hemoglobin plays an important role in improving physical function and reducing the likelihood of heart disease, but maintaining stable hemoglobin levels can be a challenge," he added.

A New Class of Drugs

Drugs given to correct anemia in dialysis patients include erythropoietin-stimulating agents (ESAs) that act by stimulating the production of red blood cells. Short-acting ESAs include epoetin alfa ( Epogen, Amgen) and epoetin beta ( NeoRecormon, Roche, which is not available in the United States); these are generally administered 3 times per week. Darbepoetin alfa ( Aranesp, Amgen) is a long-acting novel erythropoietin-stimulating protein (NESP) and is given once a week or once every 2 weeks. CERA is the first drug of a new class of compounds and has a longer half-life and a different mechanism of action at the receptor sites involved in stimulating red blood cell production.

In these 3 studies, CERA was compared with the short-acting ESAs epoetin alfa and beta and with the long-acting ESA darbepoetin alfa. At study entry, patients were age 18 years or older, on dialysis, with stable hemoglobin levels of 10.5 to 13.0 g/dL and adequate iron status. They were randomized as follows in the 3 studies:

  • Intravenous (IV) CERA vs IV epoetin alpha or beta — 673 dialysis patients receiving IV epoetin alfa or beta 1 to 3 times a week were randomized to continue their existing regimen or to be given IV CERA, either once every 2 weeks or once a month.

  • Subcutaneous (SC) CERA vs SC epoetin alfa or beta — 572 dialysis patients receiving SC epoetin alfa or beta treatment 1 to 3 times a week were randomized to continue their existing regimen or receive SC CERA either once every 2 weeks or once a month.

  • IV CERA vs IV darbepoetin alfa — 313 dialysis patients receiving IV darbepoetin alfa once every 1 to 2 weeks were randomized to continue their existing regimen or to be treated with IV CERA once every 2 weeks.

Noninferiority Demonstrated

The primary end point in each study was the mean change in hemoglobin between baseline and evaluation at weeks 29 to 36. Noninferiority was defined as a difference in the end point that was above −0.75 g/dL in the group treated with CERA compared with the group continuing to receive existing therapy.

CERA was found to be well tolerated and noninferior to existing treatment.

Maintenance of Hemoglobin (Hb) Levels, CERA vs Existing Therapies
Treatments Being Compared
Difference in Hb,
g/dL (97.5% CI)*
IV CERA 1x/2 wks vs IV epoetin alfa/beta 1–3 x/wk
0.004 (−0.21 to 0.22)
IV CERA 1x/mo vs IV epoetin alfa/beta 1–3x/week
0.05 (−0.17 to 0.27)
SC CERA 1x/2 wks vs SC epoetin alfa/beta 1–3 x/wk
0.14 (−0.09 to 0.38)
SC CERA 1x/mo vs SC epoetin alfa/beta 1–3x/wk
−0.02 (−0.26 to 0.21)
IV CERA 1x/2 wks vs IV darbepoetin alfa 1x/1–2 wks
0.18 (−0.04 to 0.40)
*Difference in the mean change in Hb at week 29–36 compared with baseline in patients treated with CERA vs those who continued receiving existing therapy.
CERA = continuous erythropoietin receptor activator (Mircera).
CI = confidence interval.
IV = intravenous.
SC = subcutaneous.

"There may be newfound office efficiencies if dosing can be once monthly," Dr. Levin told Medscape. "The big benefit that I see from Mircera is the actual administration of the drug once a month rather than 3 times per week. It is a question of convenience and also of practical importance. Much time is spent by nurses and physicians on algorithms for hemoglobin control. Often, many dose changes are made during the month. The stability we have seen here and the ability to change from a stable epoetin dose to a stable and constant hemoglobin level in treating with Mircera has been impressive."

"These preliminary results from the CERA trials are exciting and I believe are consistent with what has been observed with other long-acting ESAs; they are effective at rather long dosing intervals," Jeffrey S. Berns, MD, from the University of Pennsylvania School of Medicine, Philadelphia, remarked in a comment to Medscape. He noted that even the short-acting ESA that is available in the United States can be and has been used at extended dosing intervals, particularly in patients with chronic kidney disease who are not on dialysis.

He added that since dose adjustments will be made less frequently with a long-acting ESA, there should be fewer subtarget and above-target fluctuations and less week-to-week variability in hemoglobin levels, but it is not clear whether this will translate into any demonstrable clinical effect on patients. "It would be interesting to learn whether CERA dosed every 2 or 4 weeks is superior to a short-acting ESA dosed similarly and what doses of the short-acting ESA would be comparable, if at all. It will certainly be interesting going forward to learn more about the clinical differences, if any, between darbepoetin alfa and CERA," he concluded.

The 3 studies were supported by Hoffmann-La Roche Inc. Dr. Levin receives research funding from Hoffmann-La Roche Inc. Dr. Berns is a consultant for Amgen.

43rd ERA-EDTA Annual Meeting: Abstracts SO023, SP424, SP425. Presented July 16, 2006.


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