Romiplostim

Romiplostim
Mass / length primary structure	269 ​​amino acids
Secondary to quaternary structure	Homodimer (59 kDa)
Identifier
External IDs	CAS number : 4267639-76-9
Drug information
ATC code	B02 BX04
Drug class	Thrombopoietin receptor agonist

Romiplostim (trade name Nplate ; manufacturer Amgen ) is a drug from the group of thrombopoietin receptor agonists for the treatment of patients with immune thrombocytopenia (idiopathic thrombocytopenic purpura, ITP, Werlhof's disease) . Romiplostim is the first thrombopoietic agent to be approved in Europe.

The molecular formula of Romiplostim is C ₂₆₃₄ H ₄₀₈₆ N ₇₂₂ O ₇₉₀ S ₁₈ .

Clinical information

Application areas (indications)

Romiplostim is indicated for the treatment of adult, splenectomized patients with chronic idiopathic thrombocytopenic purpura (ITP) who are refractory (i.e. inactive or insensitive) to other therapies (e.g., corticosteroids or immunoglobulins). The use of Nplate can be considered as second-line therapy for adult, non-splenectomized patients for whom surgery is contraindicated.

Treatment with romiplostim resulted in a dose-dependent increase in platelet counts in patients with immune thrombocytopenia (idiopathic thrombocytopenic purpura, ITP, Werlhof's disease) in clinical studies .

Type and duration of application

Treatment should be under the guidance of a doctor experienced in the treatment of haematological disorders. After reconstitution of the powder, the Romiplostim solution for injection is administered subcutaneously. Romiplostim should be used once a week.

Contraindications (contraindications)

Hypersensitivity to the active substance, to any of the excipients or to proteins derived from E. coli. Liver dysfunction (risk of portal vein thrombosis).

Use during pregnancy and breastfeeding

There are no clinical data on the exposure of romiplostim in pregnant women. Romiplostim must not be used during pregnancy unless clearly necessary. It is not known whether romiplostim is excreted in breast milk, but excretion is likely and a risk to the breast-fed child cannot be excluded.

Adverse effects (side effects)

Very common: headache, for other side effects see p. Specialist info.

Pharmacological properties

Mechanism of action (pharmacodynamics)

Romiplostim is an Fc-peptide fusion protein ("peptibody") that activates intracellular transcription processes via the signaling pathway of the thrombopoietin receptor (TPO receptor, also known as cMpl) to increase platelet production.

Other Information

Orphan drug

Romiplostim was granted orphan drug status by the Food and Drug Administration (FDA) back in 2005 . The term is used for drugs that are used to treat very rare diseases.

History (admission)

In August 2008, Nplate was approved by the Food and Drug Administration (FDA) for the US market, followed by approval for the European market by the EU Commission in February 2009 .

Studies

Admission Studies

In Phase III approval studies, romiplostim resulted in significantly higher sustained overall platelet response rates compared to placebo, regardless of whether the patients were splenectomized or not. In addition, the patients treated with romiplostim were able to reduce or discontinue the dose of other ITP medications more often and had to resort to emergency medication significantly less often.

Approval studies have been conducted in both splenectomized patients with chronic ITP and non-splenectomized patients.

Long-term study

Patients who had completed one of the previous studies with romiplostim and whose platelet count had dropped to ≤ 50 × 10 ⁹ / l could be enrolled in an open-label, single-arm, multicenter long-term study. As in the previous studies, the participating patients were at least 18 years old and had diagnosed ITP. They were allowed to keep other ITP medications ( corticosteroids , danazol, and azathioprine ) at a constant dose. Enrollment began in June 2004 and was completed by December 2009. A total of 142 patients received romiplostim at 36 centers in the United States and Europe. In the previous studies, 106 patients (75%) were allocated to the romiplostim group and 36 patients (25%) to the control group. Until July 2007, these patients were treated with romiplostim for an average of 69 weeks, up to a maximum of 156 weeks; the data analysis extends up to the 144th week.

The median platelet count rose steeply in the first 4 weeks, then only slowly up to and including week 16. The platelet counts then remained in a range between 61 and 149 × 10 ⁹ / l through week 144 . The results of this long-term study show that most patients on long-term treatment with romiplostim experienced platelet responses with no evidence of tachyphylaxis. The frequency of adverse events in this study was the same as in the Phase III pivotal studies.

Myelodysplastic Syndrome (MDS)

Data from a randomized clinical trial in patients with myelodysplastic syndrome (MDS) -associated thrombocytopenia showed an increase in the number of cases of disease progression to acute myeloid leukemia (AML) and transient increases in blasts when treated with romiplostim compared with placebo .

literature

• Recommendations of a joint expert group of the DGHO, DGTI and GTH: Diagnosis and therapy of immune thrombocytopenia . In: Oncology 2010 . August 33.

Web links

• DHG: German Haemophilia Society for Combating Bleeding Diseases eV
• www.itp.de
• Werlhof's disease self-help group
• www.nplate.de
• Orphan drug list from the Association of Research-Based Pharmaceutical Manufacturers

Individual evidence

1. ↑ ^{a b c d e f g} Specialist information from the Swiss Medicines Compendium: Nplate , accessed on April 21, 2013.
2. ↑ ^{a b} Kuter DJ, Bussel JB, Lyons RM, et al. : Efficacy of romiplostim in patients with chronic immune thrombocytopenic purpura: a double-blind randomized controlled trial . In: The Lancet . 371, No. 9610, February 2008, pp. 395-403. doi : 10.1016 / S0140-6736 (08) 60203-2 . PMID 18242413 .
3. ↑ Rote-Hand-Brief (PDF; 1.7 MB) from December 15, 2010
4. ^ Committee for Orphan Medicinal Products (COMP)
5. ↑ Press release FDA .
6. ↑ Summary of the European Public Assessment Report (EPAR) .
7. ↑ Newland A, Caulier MT, Kappers-Klunne M, et al .: An open-label, unit dose-finding study of AMG 531, a novel thrombopoiesis-stimulating peptibody, in patients with immunethrombocytopenic purpura . In: Br J Haematol . . 135, No. 4, 2006, pp. 547-553. doi : 10.1111 / j.1365-2141.2006.06339.x .
8. ↑ Bussel JB, Kuter DJ, Pullarkat V, Lyons RM, Guo M, Nichol JL .: Safety and efficacy of long-term treatment with romiplostim in thrombocytopenic patients with chronic ITP . In: Blood . 113, No. 10, 2009, pp. 2161-2171. doi : 10.1182 / blood-2008-04-150078 .
9. ↑ Rote-Hand-Brief (PDF; 374 kB) from September 19, 2011

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