Nplate™ (romiplostim) is indicated to raise the platelet levels in splenectomized and non-splenectomized adults with chronic ITP

MISSISSAUGA, ON. (June 23rd, 2009) – Amgen Canada announced today that Health Canada has issued a Notice of Compliance (NOC) for Nplate^TM (romiplostim), the first and only platelet producer approved in Canada for the treatment of thrombocytopenia in splenectomized (spleen removed) and non-splenectomized adults with chronic immune (idiopathic) thrombocytopenic purpura (ITP).  Nplate™ works by raising and sustaining platelet counts, representing a novel approach for the long-term treatment of this chronic disease.

Chronic ITP is a serious autoimmune disease characterized by low platelet numbers, which can lead to serious bleeding events.

“Nplate^TM represents a different way to treat chronic ITP. Unlike other treatments for the disease such as steroids and other medications that suppress the patient’s immune system, or surgical removal of the spleen, Nplate^TM helps the body make more platelets in the same way that the hormone in your body called thrombopoietin does,” says Dr. Linda Vickars, Clinical Professor-Division of Hematology, University of British Columbia. “Nplate^TM stimulates the bone marrow to produce more platelets, which, by doing so, may help prevent bruising and bleeding.”

The Health Canada approval of Nplate^TM was based on efficacy and safety results from two pivotal Phase III studies of adult patients with chronic ITP, including both splenectomized and non-splenectomized patients .ⁱ  

Specifically, non-splenectomized patients had a 61 per cent durable platelet response (n=25/41, p<0.0001) and a 27 per cent transient platelet response (n=11/41, p<0.0001), while splenectomized patients had a 38 per cent durable platelet response (n=16/42, p=0.0013) and a 41 per cent transient platelet response (n=17/42, p=0.0013).ⁱⁱ  Combined data from both trials show clinically relevant bleeding events were significantly reduced by half in patients treated with NplateTM compared to placebo (15 per cent vs. 34 per cent).ⁱⁱⁱ 

"We are so grateful to have a medication that has been developed and tested specifically for this rare patient population.  Nplate^TM offers new hope for the treatment of chronic ITP," says Durhane Wong-Rieger, President of the Canadian Organization for Rare Disorders.

Nplate™ is approved for the treatment of chronic ITP in the United States, Australia and in the EU.

About Nplate^TM
NplateTM, Amgen's first peptibody, works similarly to thrombopoietin (TPO), a natural protein in the body, but exhibits no sequence similarity to TPO. Nplate^TM stimulates the TPO receptor, which is necessary for growth and maturation of bone marrow cells that produce platelets.

Nplate^TM is indicated to increase the platelet levels in adult patients with chronic ITP:

• Who are nonsplenectomized and have had an inadequate response or are intolerant to corticosteroids and/or immunoglobulins;

• Who are splenectomized and have had an inadequate response to splenectomy.

Nplate^TM has been used alone or in combination with other ITP therapies such as corticosteroids, azathioprine or danazol.

Nplate^TM is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation or component of the container, or with a known history of sensitivity or allergy to any E. coli-derived product.

 

Nplate^TM should be prescribed and monitored only by qualified healthcare providers.

Nplate^TM should be used only in patients whose degree of thrombocytopenia and clinical condition increase the risk for bleeding.  Nplate^TM should not be used in an attempt to normalize platelet counts.  

Nplate™ administration increases the risk for development or progression of reticulin fiber deposition within the bone marrow. Overall, in clinical studies, 10 of 271 (3.7%) patients were observed to have reticulin in the bone marrow. Nplate™ was discontinued in 4 of the 271 (1.5%) patients because of bone marrow reticulin deposition. Six (2.2%) additional patients had reticulin observed upon bone marrow biopsy. All 10 patients with bone marrow reticulin deposition had received Nplate™ doses ≥ 5 mcg/kg and six had received doses ≥ 10 mcg/kg.

Progression to marrow fibrosis with cytopenias was not reported in the controlled clinical studies. In the extension study, one patient with ITP and hemolytic anemia developed marrow fibrosis with collagen during Nplate™ therapy. Clinical studies have not excluded a risk of bone marrow fibrosis with cytopenias with Nplate™. The long term risk for progression to myelofibrosis is unknown.

Platelet counts above the normal range present a theoretical risk for thrombotic / thromboembolic complications; dose adjustment guidelines should be followed.

In the placebo-controlled studies, headache was the most commonly reported adverse drug reaction. In nonsplenectomized patients, headaches occurred in 26% of patients receiving Nplate^TM and 30% of patients receiving placebo. In splenectomized patients, headaches occurred in 43% of patients receiving Nplate^TM and 33% of patients receiving placebo. Headaches were usually of mild or moderate severity.

In a Phase 3 placebo-controlled study, adverse drug reactions ≥1% in nonsplenectomized patients were: headache (26.2%, placebo: 30%), arthralgia (23.8%, placebo: 25%), pain in extremity (19%, placebo: 10%), dizziness (16.7%,  placebo: 0%), insomnia (11.9%, placebo: 10%), abdominal pain (11.9%, placebo: 0%), shoulder pain (11.9%, placebo: 0%), myalgia (7.1%, placebo: 5%), dyspepsia (4.8%, placebo: 0%), paresthesia (4.8%, placebo: 0%).

In a Phase 3 placebo-controlled study, adverse drug reactions ≥1% in splenectomized patients were: headache (42.9%, placebo:  33.3%), arthralgia (28.6%, placebo: 14.3%), myalgia (21.4%, placebo: 0%), insomnia (19%, placebo: 4.8%), dizziness (16.7%, placebo: 0%), abdominal pain (9.5%, placebo: 0%), dyspepsia (9.5%, placebo: 0%), pain in extremity (7.1%, placebo: 0%), paresthesia (7.1%, placebo: 0%), shoulder pain (4.8%, placebo: 0%), bone marrow disorder (2.4%, placebo: 0%). Actual frequency of bone marrow disorder is unknown since routine bone marrow biopsies were not performed.

In a long-term ITP extension study, where the mean time on study for the 136 subjects in the safety analysis set was 45 weeks (SD, 34.7 weeks; range, 1 to 122 weeks), incidence of adverse drug reactions ≥1% were: headache (30.9%), arthralgia (19.9%), dizziness (12.5%), pain in extremity (12.5%), abdominal pain (9.6%), insomnia (9.6%), myalgia (6.6%), paresthesia (6.6%), dyspepsia (4.4%), bone marrow disorder (2.9%), shoulder pain (2.2%).

About Amgen
Amgen discovers, develops and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science’s promise by bringing safe and effective medicines from lab, to manufacturing plant, to patient. Amgen therapeutics has changed the practice of medicine, helping millions of people around the world in the fight against cancer, kidney disease, rheumatoid arthritis, and other serious illnesses. With a broad and deep pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people’s lives. To learn more about our pioneering science and our vital medicines, visit http://www.amgen.ca/.

CONTACT: 

Sabrina Paiva
Amgen Canada
(905) 285-3145
spaiva@amgen.com    

Ethan Pigott
Hill and Knowlton Canada
(416) 413-4744
ethan.pigott@hillandknowlton.ca

REFERENCES
__________________________
 ⁱ Nplate^TM Canadian product monograph, page 34/35.
 ⁱⁱ Nplate^TM Canadian product monograph, page 39.
 ⁱⁱⁱ Nplate^TM Canadian product monograph, page 26.