Amgen Inc. announced the final results from a 5-year open-label extension study investigating the long-term efficacy and safety of Nplate (romiplostim) in adult chronic Immune (idiopathic) Thrombocytopenic Purpura (ITP). Chronic ITP is a serious autoimmune disorder characterized by low platelet counts in the blood (thrombocytopenia), which can lead to serious bleeding events.
The complete data, presented as an oral presentation at the 52nd Annual Meeting and Exposition of the American Society of Haematology (ASH), demonstrated that Nplate safely and effectively maintained platelet counts in the significant majority of patients for the duration of the study.
"In this study, nearly all Nplate-treated patients were able to maintain platelet counts within the target range for more than five years," said David J. Kuter, MD, chief of Haematology, Massachusetts General Hospital, Boston and lead investigator. "The most common and serious adverse events were consistent with those reported in past studies and did not increase over time. These results, from the largest and longest interventional study of TPO-mimetic exposure to date, provide physicians and their patients with important information on the continued long-term safety and efficacy of Nplate."
In the long-term extension study, Nplate maintained platelet counts within a range of 50,000 to 200,000 platelets per micro-liter in the majority of adult patients with chronic ITP with minimal decreased or increased dose adjustments for up to 277 weeks. Over the course of the study, a platelet count of greater than or equal to 50,000 platelets per micro-liter was achieved by 95 per cent of 292 patients receiving Nplate, and the median platelet count remained greater than or equal to 50,000 platelets per micro-liter for the duration of the study after week one. Patients were treated for a median of 78 weeks with a maximum duration of 277 weeks and 33 percent of patients had previously undergone splenectomy.
In addition, results showed that adverse event rates in patients treated with Nplate were consistent with those reported in previous studies and did not increase with longer duration of treatment. The most common side effects were mild and included headache (38 per cent), nasopharyngitis (34 per cent) and fatigue (32 per cent). Of the 37 patients who received concurrent ITP treatment at baseline, 81 per cent were able to discontinue or reduce the dose by more than 25 per cent.
This is an open-label, long-term efficacy and safety study of Nplate for the treatment of patients with chronic ITP. Nplate was administered once weekly by subcutaneous injection, with dose adjustments to maintain platelet counts in the target range (50,000 to 200,000 platelet count per microliter). The primary study objective was to determine long-term safety of Nplate. Secondary study objectives were to evaluate long-term platelet responses and the use of concurrent ITP therapies.
In patients with ITP, platelets - blood elements needed to prevent bleeding - are destroyed by the patient's own immune system. Recent data also suggest that low platelet counts in the blood may be caused by the inability of the body's natural processes to produce platelets. Low platelet counts leave adult ITP patients open to sudden serious bleeding events. The risk for serious bleeding events increases when platelet counts drop to less than 30,000 platelets per micro-liter; normal counts range from 150,000 to 400,000 platelets per micro-liter.
ITP has historically been considered a disease of platelet destruction although recent data suggest that the body's natural platelet production processes in ITP are unable to compensate for low levels of platelets in the blood. Increasing the rate of platelet production may address low platelet levels associated with ITP. Currently, there are approximately 90,000 adult chronic ITP patients in Europe and the United States (US). ITP affects about twice as many adult women as men.
Nplate is the first platelet producer approved in the European Union (EU), Canada, Australia, Russia, Mexico, Switzerland and the U.S. Nplate also has received orphan designation for chronic ITP in the US (2003), the EU (2005), Switzerland (2005), Japan (2006) and Mexico (2010).
Nplate is the first treatment FDA approved treatment specifically for adult chronic ITP. It is also being investigated for potential use in children ages 12 months to 18 years old with persistent severe thrombocytopenia, MyeloDysplastic Syndromes (MDS) and Chemotherapy-Induced Thrombocytopenia (CIT).
In the US, Nplate is indicated for the treatment of thrombocytopenia in patients with chronic immune ITP who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy. Nplate should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increases the risk for bleeding and it should not be used in an attempt to normalize platelet counts.
In the EU, Nplate is indicated for the treatment of splenectomized adult chronic ITP patients who are refractory to other treatments (e.g. corticosteroids, immunoglobulins). Nplate may be considered as a second-line treatment for adult non-splenectomized ITP patients for whom surgery is contraindicated.
Nplate was named as a recipient of the US Prix Galien2009 "Best Biotechnology Product" award and also received the 2009 Scrip Awards for "Best New Drug." Nplate has also been honoured with numerous awards throughout the EU, including a 2010 Prix Galien in France in the category of "Drugs for Rare Diseases." In September 2010, Nplate was awarded the 2010 International Prix Galien Award, an award granted every two years which recognizes the "best of the best" selected from previous national Prix Galien award recipients.
Serious adverse reactions associated with Nplate in clinical studies were bone marrow reticulin deposition and worsening thrombocytopenia after Nplate discontinuation. Additional risks include bone marrow fibrosis, thrombotic/thromboembolic complications, lack or loss of response to Nplate, and haematological malignancies and progression of malignancy in patients with a pre-existing haematological malignancy or MDS. Nplate is not indicated for the treatment of thrombocytopenia due to MDS or any cause of thrombocytopenia other than chronic ITP.
In the US, Nplate is available only through a restricted distribution program called Nplate NEXUS (Network of Experts Understanding and Supporting Nplate and Patients) Program. In the placebo-controlled studies, headache was the most commonly reported adverse drug reaction.
The most common side effects are headache, fatigue, arthralgia, myalgia, injection site bruising, injection site pain, oedema peripheral, dizziness, muscle spasms, nausea, contusion, diarrhoea, bone marrow disorder, influenza-like illness, insomnia and pruritus.
Reoccurrence of thrombocytopenia and bleeding after cessation of treatment and increased bone marrow reticulin have been associated with Nplate treatment in the clinical trials. Thrombotic/thromboembolic complications, progression of existing hematopoietic malignancies or MDS, and effects on red and white blood cells are all potential risks associated with Nplate treatment. As with all therapeutic proteins, patients may develop antibodies to the therapeutic protein.
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