This document discusses romiplostim, a thrombopoietin receptor agonist approved for the treatment of chronic immune thrombocytopenia (ITP). Key points: - A clinical trial found romiplostim significantly increased platelet counts in patients with chronic ITP compared to placebo, allowing over 70% of patients to reduce or discontinue other ITP medications. - Common adverse events included headache, fatigue, and joint pain. Serious risks included bone marrow fibrosis and potential progression to myelodysplastic syndrome or leukemia. - Romiplostim is a fusion protein that mimics thrombopoietin to stimulate platelet production. It provides an alternative to other ITP therapies like cortic

1. ROMIPLOSTIM
A Novel
Thrombopoiesis-
Stimulating Agent
Dr Anu Chandran
1

2. Immune thrombocytopenic
purpura
• Autoimmune disease
• Antibodies [IgG] detected
against platelets
• Isolated thrombocytopenia
• Rash and increased
tendency to bleed
• Two pathogenesis
1.Antibodies causing platelet
destruction
2.Impaired production of
thrombopoietin
2

3. Treatment of ITP
• Steroid
• IVIG
• Vincristin/Vinblastin
• Cyclophosphamide
• Azathioprine
• Rituximab
• Anti-D
• Surgery - splenectomy
3

4. Efficacy and safety of
romiplostim in patients
with primary immune
thrombocytopenia
Lancet. 2008 February ,volume
371 Number 9610
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5. 5
PURPOSE- The safety
and efficacy of romiplostim were
evaluated.
double-blinded placebo controlled
Study group –
125 patients with chronic ITP
Completed at least one prior
therapy
Baseline platelet counts
≤ 30,000/mcL.

6. 6
STUDY GROUP 1
Non-splenectomised
Inadequate response or were
intolerant to prior therapies.
Diagnosed with ITP for
approximately 2 years .
STUDY GROUP 2
Splenectomised and continued to
have thrombocytopenia.
Diagnosed with ITP for
approximately 8 years
Both placebo-controlled groups -
allowed to continue receiving
previous medical treatments
throughout the study

7. INTERVENTION
• Starting dose of romiplostim
1 μg/kg or placebo.
• Patients received single
subcutaneous weekly
• Injections for 24 weeks.
• Doses were adjusted to
maintain (50 to 200 x 109
/l)
platelet counts.
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8. RESULTS
8
OutcomeOutcome
Study 1Study 1
ssplenectomyplenectomy
Study 2Study 2
nonnon
splenectomysplenectomy
PlaceboPlacebo RomiplostimRomiplostim PlaceboPlacebo RomiplostimRomiplostim
OverallOverall
PlateletPlatelet
ResponceResponce
(%)(%)
00 79%79% 14%14% 88%88%
All p-values < 0.01

9. Adverse Events
9
AdverseAdverse
eventevent
PlaceboPlacebo
RomiplostimRomiplostim
FatalFatal 7%7% 1%1%
BleedBleed 61%61% 57%57%

10. Other adverse events (%)
10
TermTerm PlPl
RomiplostimRomiplostim
ArthralgiaArthralgia 20%20% 26%26%
DizzinessDizziness 00 17%17%
InsomniaInsomnia 7%7% 16%16%
MyalgiaMyalgia 2%2% 14%14%
Extremity painExtremity pain 5%5% 13%13%
AbdominalAbdominal
painpain
00 11%11%
Shoulder painShoulder pain 00 8%8%
DyspepsiaDyspepsia 00 7%7%
ParesthesiaParesthesia 00 6%6%

11. Summary of efficacy
100% splenectomised patients
who were receiving romiplostim
were able to reduce the dose by
more than 25% or discontinue
the concurrent ITP medical
therapies
73% non-splenectomised
patients were able to reduce
the dose by more than 25% or
discontinue concurrent ITP
medical
11

12. Summary of the safety
profile
The most serious adverse
reactions that may occur during
Romiplostim treatment include:
 reoccurrence of
thrombocytopenia
 bleeding after cessation of
therapy
increased bone marrow
reticulin,
 thrombotic/thromboembolic
complications,
progression of existing MDS to
AML.
12

13. Romiplostim
FUSION PROTEIN
THROMBOPOETIN ANALOG
Produced by recombinant DNA
technology in E coli.
Orphan drug [2003]
Developed by AMGEN
Trade name -Nplate
FDA Approval Date: 08/2008
250 mcg and 500 mcg powder

14. DOSE
14
• The initial dose of romiplostim
is 1 μg/kg based on actual
body weight
 Average dose: 2
mcg/kg/wk
 Max dose: 10
mcg/kg/wk
 Administered at weekly
intervals s/c
The goal the count
above 50,000 per cubic
millimeter (mm3
) of blood

15. Mechanism of Action
Fc-peptide fusion protein
Binds to thrombopoietin
receptor.[JAK STAT]
Activates intracellular
transcriptional pathways
Increased platelet
production 15

16. Indication[2008]
For the treatment of
thrombocytopenia in adult
patients with chronic ITP:
• who are non-splenectomized
and have an insufficient
response or are intolerant to
corticosteroids and/or
immunoglobulins.
• who are splenectomized and
have an insufficient response
to splenectomy.
.
16

17. Pharmacokinetics:
- Peak: 7 to 50 hr (median 14 hr)
- t1/2
:1-34 days (median 3.5 days).)
Elimination
•Dependent on the TPO receptor on
platelets.
•High platelet counts are
associated with low serum
romiplostim concentrations.

18. Adverse drug reactions
-  Headache
 Fatigue
 Epistaxis
 Confusion
 Arthralgia
 Upper respiratory infection
 Dizziness
 Diarrhea
 Insomnia
 Myalgia
 Bleeding

19. 19
Contraindications
1.Hypersensitivity
2.Within 24 hr of receiving
myelosuppressive
chemotherapy or radiation
therapy
3.>10% leukemic myeloid
blasts in bone marrow or
peripheral blood
Interactions
No formal drug interaction
studies to date.

20. Preclinical Safety Data
 Reversible myelofibrosis
has been observed in the
bone marrow of rats
 Formation of neutralising
antibodies.
 Evidence of increased
post-implantation LOSS
 Cross the placental
barrier in rats
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21. 21
Warnings:
- Risk for bone marrow
fibrosis
- Hematologic malignancies
-Thromboembolism
-Immunogenicity
Precautions
- Hepatic impairment
- Renal impairment
- Pediatrics – no data available
- Pregnancy – Category C

22. Long-term safety and
tolerability of romiplostim
in patients with primary
immune thrombocytopenia:
a pooled analysis of 13
clinical trials.
CONCLUSION
long-term romiplostim
treatment is well tolerated,
with no new safety signals,
even in patients treated for
up to 5 yr.
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23. THANK YOU
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