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Hematide for the Treatment of Anemia: An Expert Interview With Iain C. Macdougall, BSc, MD, FRCP


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Editor's Note:

Also in the development stages for the treatment of anemia of chronic kidney disease are the erythropoietin-mimetic peptides. These agents have the same mechanism of action as endogenous and recombinant erythropoietin, although they are structurally unrelated. One agent in this class, Hematide, is in phase 2 of clinical development. As a pegylated peptide, Hematide has a long duration of action that allows for once monthly dosing. Other possible benefits of Hematide include its stability at room temperature and a lack of crossreactivity with antierythropoietin antibodies. Kimberly Fricke, PharmD, interviewed Iain C. Macdougall, BSc, MD, FRCP, at the 2006 American Society of Nephrology meeting in San Diego, California, on the possible advantages of erythropoietin-mimetic peptides. Dr. Macdougall is a Consultant Nephrologist and Honorary Senior Lecture at King's College Hospital in London, United Kingdom.

Medscape: There is currently a great deal of discussion in the clinical community relating to the design and mechanism of action of synthetic peptide-based erythropoiesis-stimulating agents and recombinant products. Can you provide clarification on the impact of the design of erythropoiesis agent on an individual's physiologic response?

Dr. Iain C. Macdougall: Over the past 20 years or so, we've come to understand the mechanism of action of erythropoietic agents, and at the moment, all the agents we have available interact with the erythropoietin receptor, turn on the erythropoietin receptor, and stimulate erythropoiesis by an intracellular signaling cascade. The erythropoietin mimetic peptides do that too. They do that in the same way as the first generation epoetins do, in the same way as darbepoetin alfa does, and yet these are synthetic peptides that will do the same job as the initial agents.

Medscape: At the 2005 annual meeting of the American Society of Nephrology, data from clinical studies involving a synthetic peptide-based erythropoiesis-stimulating agents were reported in a population of patients with anemia of chronic kidney disease.[1] Can you tell us more about the outcome of this research?

Dr. Iain C. Macdougall: Data at the ASN meeting in 2005 were presented on Hematide, which is a new erythropoiesis agent. It's a synthetic peptide and those data show this agent is able to turn on the erythropoietin receptor to stimulate erythropoiesis and to correct the anemia associated with chronic kidney disease. It seems to be relatively safe, although, obviously these are preliminary results and they need to be confirmed in larger phase 3 trials.

Medscape: Are additional studies currently under way?

Dr. Iain C. Macdougall: Additional studies for Hematide are currently under way. The agent is in phase 2 of its clinical trial program; phase 3 is planned. At the ASN meeting in San Diego in November 2006, some of the phase 2 data were presented, and the phase 3 program will start next year.[2,3]

Medscape: Now that we have a better understanding of the physiological actions of the different agents, can you provide some clinical insight as to the potential advantages and disadvantages of the different agents?

Dr. Iain C. Macdougall: We've come a long way over the past 20 years with the erythropoietic agents from the very early days in the 1980s when we had the first-generation agents such as recombinant human erythropoietin or epoetin. We moved into the 1990s when we had a second-generation agent, darbepoetin alfa, and this had the advantage of slightly less frequently dosing from 3 times a week to once a week. And we now move into the present where we have additional agents in clinical trials for even less frequent dosing such as continuous erythropoiesis receptor activator (CERA), which can be given up to once a month, Hematide, the one we're talking about today which is the synthetic peptide also can be given once a month, and the hypoxia-inducible factor (HIF) stabilizers, which may be able to be given orally.

The other advantages of Hematide are several-fold. One, it is not a protein. It's the first nonprotein agent to be so advanced in phase 2 clinical trials and that may have potential advantages in term of stability. It may not need to be kept in a fridge, and also in terms of cost, it's much cheaper to make a synthetic peptide as a manufacturing process than a biological, which requires a cell line. So perhaps this will reduce the cost of these agents, which would obviously be another serious advantage.

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