Researchers have reported that romiplostim (AMG531) is an effective agent for the treatment of chronic immune thrombocytopenic purpura (ITP). The results of several clinical trials involving romiplostim were presented at the 2007 meeting of the American Society of Hematology, December 8-10 in Atlanta Georgia.

Thrombopoetin (TPO) or thrombopoetin-like drugs have had limited success for the treatment of thrombocytopenia, primarily due to antibody production. Currently, Neumega® (oprelvekin) is the only FDA approved drug for treating or preventing thrombocytopenia and it has not been very widely used. The second generation of TPO-like agents has been developed by identifying peptides that bind the TPO receptor with high affinity. Because they bear no structural resemblance to TPO, but still bind and activate the TPO receptor, these compounds are called TPO mimetics.  Several peptides have been identified, and they have been further modified to both prolong their half-life in plasma as well as to increase their efficiency in activating the TPO receptor.  The theoretical advantage of these compounds over standard recombinant TPO is that they bear little structural similarity with native TPO, and should not trigger auto-immune anti-TPO antibodies like PEG-MDGF. Romiplostim is a thrombopoiesis stimulating Fc-peptide fusion protein (“peptibody”) that increases platelet production in patients with chronic ITP and myelodysplastic syndromes (MDS).

Chronic ITP is a disease associated with decreased megakaryocytes and decreased TPO responses. At ASH 2007 Researchers from several US and European centers presented the results of a randomized trial of romiplostim in patients with chronic ITP who had been splenectomized.¹ Sixty-three patients with chronic ITP were randomized on a 2:1 basis to receive romiplostim or placebo for 24 weeks. Most of the patients had their disease for 8-9 years, were splenectomized and had platelet counts less than 30,000. The overall response rate was 79% in the romiplostim group and 0% in the placebo group and 38% of the responses were durable. Patients in the romiplostim group were more likely to have reduced therapies for chronic ITP.

Researchers also reported the effects of romiplostim in patients with chronic ITP who had not been splenectomized.² Sixty-two patients with chronic ITP who had not been splenectomized were randomized on a 2:1 basis to receive romiplostim or placebo. A durable platelet response (>50,000 for more than 6 weeks) was achieved in 61% of patients receiving romiplostim and 4.8% of patients receiving placebo. Overall response rate (durable or transient response) was observed in 88% of patients receiving romiplostim and 14% of patients receiving placebo. Romiplostim also reduced the use of rescue medications compared to placebo. Romiplostim was considered to be well tolerated.

The effects of long-term dosing of romiplostim in patients with chronic ITP were also reported.³ This study enrolled 136 patients with chronic ITP with the longest treatment duration being 122 weeks. Baseline platelet counts in this group of patients averaged 18,000 and 60% had undergone splenectomy. The most frequent adverse events were headache, contusion, fatigue, diarrhea, epistaxis, pharyngitis and arthralgia. Eleven patients were deemed to have serous side effects of romiplostim including three withdrawals from study due to vaginal hemorrhage, increased reticulin in the bone marrow and a case of monoclonal gammopathy. There was no association between symptoms and increased duration of therapy with romiplostim. One patients developed antibodies romiplostim. A platelet response was achieved by 82% of patients as measured by increases to >50,000 and doubling of baseline platelet counts. The median time to first response was two doses of romiplostim. Thirteen of 30 patients receiving concurrent therapy had such therapy discontinued after treatment with romiplostim. These authors concluded that “individualized weekly doses of Rhomiplastin [romiplostim] provide a therapeutic option for long-term treatment of chronic ITP.”

Patients with chronic ITP receiving romiplostim were also less likely to receive immunoglobulin (IVIG or Anti D) than patients receiving placebo.⁴ This study evaluated the use of immunoglobulin, IVIG or Anti D, as rescue medications for patients receiving Rhomiplastin or placebo in a large randomized trial. The probability of immunoglobin treatment was 50% in the control group and 10% in the romiplostim group. These authors concluded that romiplostim treatment “was associated with significantly reduced immunoglobulin use in both splenectomized and nonsplenectomized patient with chronic ITP.”

Comments: These are very remarkable data and of potentially great importance to patients with chemotherapy induced thrombocytopenia. Ongoing clinical trials will determine if romiplostim is effective in chemotherapy induced thrombocytopenia.

Related News:

AMG 531 Maybe Effective in Treating Thrombocytopenia in Patients with MDS (06/11/2007)

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