Nplate® (romiplostim) Now Approved For Earlier Use In Adults With Immune Thrombocytopenia

(STL.News) –  Amgen (NASDAQ:AMGN) today announced that the U.S. Food and Drug Administration (FDA) approved Amgen’s Supplemental Biologics License Application (sBLA) for Nplate® (romiplostim) to include new data in its U.S. prescribing information showing sustained platelet responses in adults with immune thrombocytopenia (ITP), a rare, serious autoimmune disease characterized by low platelet counts.  The updated indication expands treatment with Nplate to newly diagnosed and persistent adult ITP patients who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy.  In December of last year, the FDAapproved another sBLA for Nplate in the treatment of pediatric patients with ITP.

“These new data are the first of their kind to prospectively examine treatment-free remission as an outcome for patients with ITP. Thirty-two percent of patients who received Nplate soon after an insufficient response to the first course of steroids maintained platelet response for at least six months without Nplate or any other ITP therapy,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen.  “This approval will provide patients the opportunity to receive Nplate earlier in the course of their disease, potentially reducing their need for prolonged steroid use.  We are excited to make Nplate available to more patients with this rare blood disorder.”

The sBLA was based on an open-label, single-arm Phase 2 trial of adults with ITP diagnosed ≤ 6 months prior who had an insufficient response to first-line treatment, including corticosteroids (N=75).  The median time from ITP diagnosis to study enrollment was 2.2 months.  On the primary endpoint, the median number of months with platelet response (≥ 50 x 109/L) was 11 months during the 12-month treatment period (95% CI: 10, 11), with a median time to first platelet response of 2.1 weeks (95% CI: 1.1, 3.0).  Additionally, 93% (70) of patients achieved one or more platelet responses during the 12-month treatment period.  On the secondary endpoint, 32% (24) of patients achieved remission for at least six months, defined by maintaining a platelet count ≥ 50 x 109/L in the absence of Nplate and any medication for ITP (concomitant or rescue).

“Among adults with immune thrombocytopenia, there is a need for treatment options that can get patients to sustained remission,” said Caroline Kruse, president and chief executive officer, Platelet Disorder Support Association.  “The addition of this new data will help physicians and patients communicate and weigh the benefits and risks of treatment to find an appropriate treatment choice.”

The safety profile of Nplate was similar across patients, regardless of ITP duration.  The following adverse reactions (at least 5% incidence and at least 5% more frequent with Nplate compared with placebo or standard of care) occurred in Nplate patients with ITP duration up to 12 months: bronchitis, sinusitis, vomiting, arthralgia, myalgia, headache, dizziness, diarrhea, upper respiratory tract infection, cough, nausea and oropharyngeal pain.  The adverse reaction of thrombocytosis occurred with an incidence of 2% in adults with ITP duration up to 12 months.

About the Phase 2 Study
The Phase 2 study was a single-arm, open-label study designed to assess the safety and efficacy of Nplate in adult patients who had an insufficient response (platelet count ≤ 30 x 109/L) to first line therapy (N=75).  The median time from ITP diagnosis to study enrollment was 2.2 months.  Prior ITP treatments included corticosteroids, immunoglobulins and anti-D immunoglobulins.  Rescue therapies were permitted.  Patients received single weekly SC injections of Nplate over a 12-month treatment period, with individual dose adjustments to maintain platelet counts (50 x 109/L to 200 x 109/L).

About Immune Thrombocytopenia (ITP)
ITP is a rare, serious autoimmune disease characterized by low platelet counts in the blood (a condition known as thrombocytopenia) and impaired platelet production.  1 In the U.S., the estimated incidence of ITP is 6.1 per 100,000 adults annually.2 Nearly 20,000 people are newly diagnosed with ITP each year in the U.S.2

About Nplate® (romiplostim)
Nplate is a thrombopoietin (TPO) receptor agonist that mimics the body’s natural TPO and is designed to increase platelet counts in patients with ITP.3

In the U.S:

Nplate is approved for the treatment of thrombocytopenia in adult patients with ITP who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
Nplate is approved for the treatment of thrombocytopenia in pediatric patients 1 year of age and older with ITP for at least 6 months who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.
In the European Union (EU):

Nplate is approved for the treatment of chronic ITP in adults and in children age one year and older with ITP for at least six months, who have had an insufficient response to other medicines or had surgery to remove the spleen.
Nplate is also approved in 69 countries, including Canada and Australia.

For more information about Nplate, please visit www.Nplate.com.

IMPORTANT SAFETY INFORMATION

Risk of Progression of Myelodysplastic Syndromes to Acute Myelogenous Leukemia

In Nplate® (romiplostim) clinical trials of patients with myelodysplastic syndromes (MDS) and severe thrombocytopenia, progression from MDS to acute myelogenous leukemia (AML) has been observed.
Nplate® is not indicated for the treatment of thrombocytopenia due to MDS or any cause of thrombocytopenia other than ITP.
Thrombotic/Thromboembolic Complications

Thrombotic/thromboembolic complications may result from increases in platelet counts with Nplate® use.  Portal vein thrombosis has been reported in patients with chronic liver disease receiving Nplate®.
To minimize the risk for thrombotic/thromboembolic complications, do not use Nplate® in an attempt to normalize platelet counts. Follow the dose adjustment guidelines to achieve and maintain a platelet count of ≥ 50 x 109/L.
Loss of Response to Nplate®

Hyporesponsiveness or failure to maintain a platelet response with Nplate® should prompt a search for causative factors, including neutralizing antibodies to Nplate®.
To detect antibody formation, submit blood samples to Amgen (1‑800‑772‑6436).  Amgen will assay these samples for antibodies to Nplate® and thrombopoietin (TPO).
Discontinue Nplate® if the platelet count does not increase to a level sufficient to avoid clinically important bleeding after 4 weeks at the highest weekly dose of 10 mcg/kg.
Adverse Reactions

Adult ITP

In the placebo-controlled trials of adult ITP patients, headache was the most commonly reported adverse drug reaction, occurring in 35% of patients receiving Nplate® and 32% of patients receiving placebo.  Adverse drug reactions in adults with a ≥ 5% higher patient incidence in Nplate® versus placebo were Arthralgia (26%, 20%), Dizziness (17%, 0%), Insomnia (16%, 7%), Myalgia (14%, 2%), Pain in Extremity (13%, 5%), Abdominal Pain (11%, 0%), Shoulder Pain (8%, 0%), Dyspepsia (7%, 0%), and Paresthesia (6%, 0%).
The safety profile of Nplate was similar across patients, regardless of ITP duration.  The following adverse reactions (at least 5% incidence and at least 5% more frequent with Nplate compared with placebo or standard of care) occurred in Nplate patients with ITP duration up to 12 months: bronchitis, sinusitis, vomiting, arthralgia, myalgia, headache, dizziness, diarrhea, upper respiratory tract infection, cough, nausea and oropharyngeal pain.  The adverse reaction of thrombocytosis occurred with an incidence of 2% in adults with ITP duration up to 12 months.
Pediatric ITP

The most common adverse reactions experienced by ≥ 5% of patients receiving Nplate with > 5% higher incidence in the romiplostim arm across the two placebo-controlled trials were contusion (41%), upper respiratory tract infection (31%), oropharyngeal pain (25%), pyrexia (24%), diarrhea (20%), rash (15%), and upper abdominal pain (14%).
In pediatric patients of age > 1 year receiving romiplostim for ITP, adverse reactions with an incidence of > 25% in the two randomized trials were: contusion (41%), upper respiratory tract infection (31%), and oropharyngeal pain (25%).
Nplate® administration may increase the risk for development or progression of reticulin fiber formation within the bone marrow. This formation may improve upon discontinuation of Nplate®.  In a clinical trial, one patient with ITP and hemolytic anemia developed marrow fibrosis with collagen during Nplate® therapy.

INDICATIONS
Nplate® is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in adult patients with immune thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.  Nplate® is indicated for the treatment of thrombocytopenia in pediatric patients 1 year of age and older with ITP for at least 6 months who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

Nplate® is not indicated for the treatment of thrombocytopenia due to myelodysplastic syndrome (MDS) or any cause of thrombocytopenia other than ITP.  Nplate® should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding.  Nplate® should not be used in an attempt to normalize platelet counts.

Please see full Prescribing Information and Medication Guide.

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