Nplate receives positive opinion for marketing authorisation in Europe

Amgen has announced that the European Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending marketing authorisation for Nplate (romiplostim) in the European Union (EU).

The CHMP recommends Nplate for adult chronic immune (idiopathic) thrombocytopenia purpura (ITP) splenectomised patients who are refractory to other treatments (e.g. corticosteroids, immunoglobulins). Nplate may be considered as second line treatment for adult non-splenectomised patients where surgery is contra-indicated.

"Nplate will address an unmet medical need for thousands of patients in the European Union as it is a unique treatment option that increases platelet production and avoids immune suppression in adult chronic ITP patients," said Willard Dere, M.D., senior vice president and international chief medical officer at Amgen.

The novel peptibody technology upon which romiplostim is based represents a promising new approach for treating adult patients with chronic ITP, an autoimmune disorder affecting an estimated 50,000 people in the EU, which can lead to serious bleeding events that can be potentially life threatening.

Nplate, a thrombopoietin (TPO) mimetic, is a novel engineered therapeutic fusion protein with attributes of both peptides and antibodies, but is distinct from each. Nplate works similarly to TPO, a natural protein in the body. Nplate stimulates the TPO receptor, which is necessary for growth and maturation of bone marrow cells that produce platelets.

The CHMP positive opinion is based on data from two separate placebo-controlled Phase 3 studies, demonstrating that platelet counts were raised and sustained in 83 percent of patients for both splenectomised and non-splenectomised groups when treated with Nplate. Additionally, patients treated with Nplate were able to reduce or discontinue concomitant ITP and emergency medications which are often not well tolerated or whose effects are transient (i.e. corticosteroids, IVIG, Win-Rho Anti-D therapy).

Upon completion of the Phase 3 studies almost 90 percent of patients elected to subsequently enroll into the romiplostim long term extension study which demonstrated that, after three years, Nplate continued to effectively increase and sustain platelet counts. In this open label long term extension study some patients were treated for over 156 weeks and in the interim analysis the median treatment duration in this study is 65 weeks.

About Adult ITP

In patients with ITP, platelets -- or blood cells needed to prevent bleeding -- are destroyed by the patient's own immune system. Low platelet counts leave adult ITP patients open to sudden serious bleeding events, making it impossible to arrest blood flow. The risk for serious bleeding events increases when platelet counts drop to less than 30,000 platelets per microliter; normal counts range from 150,000 to 400,000 platelets per microliter. 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 available treatments (i.e., corticosteroids, immunoglobulins) have limited application due to poor tolerability or transient effects. Surgical therapy (removal of the spleen) is also available to adult patients with chronic ITP, but does not work in all cases. Currently, there are 140,000 treated chronic ITP patients in Europe and the U.S. ITP affects about twice as many adult women as men.

About Nplate

Nplate was granted approval for ITP by the regulatory bodies in Australia in July and the United States (U.S.) in August 2008. In addition to the European Union (EU), Amgen has filed for regulatory approval of Nplate in Canada and Switzerland and these applications are currently under review. Nplate has also received orphan designation for ITP in the U.S. (2003), the EU (2005), Switzerland (2005) and Japan (2006).

Nplate is the first treatment specifically developed for ITP. It is also being investigated for potential use in pediatric ITP, myelodysplastic syndrome (MDS) and chemotherapy-induced thrombocytopenia (CIT).

Important EU Nplate Safety Information

The most common side effects are headache, fatigue, arthralgia, myalgia, injection site bruising, injection site pain, oedema peripheral, dizziness, muscle spasms, nausea, contusion, diarrhea, 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 romiplostim treatment in the clinical trials. Thrombotic/thromboembolic complications, progression of existing haematopoietic malignancies or Myelodysplastic Syndromes (MDS), and effects on red and white blood cells are all potential risks associated with romiplostim treatment. As with all therapeutic proteins, patients may develop antibodies to the therapeutic protein.

Important U.S. Nplate Safety Information

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 hematological malignancies and progression of malignancy in patients with a pre-existing hematological malignancy or Myelodysplastic Syndrome (MDS). Nplate is not indicated for the treatment of thrombocytopenia due to MDS or any cause of thrombocytopenia other than chronic ITP.

In the U.S. Nplate is available only through a restricted distribution program called Nplate(TM) 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.