Study Published in New England Journal of Medicine Shows Nplate® Significantly Reduces Treatment Failure and Splenectomy Rate in Patients With Chronic ITP

THOUSAND OAKS, Calif., Nov. 10, 2010 /PRNewswire-FirstCall/ -- Amgen Inc. (Nasdaq: AMGN) today announced the publication of results from the first open-label study to compare Nplate^® (romiplostim) treatment to standard of care therapies (SOC) in non-splenectomized adult patients with chronic immune thrombocytopenia (ITP). The study results, which were published today in the New England Journal of Medicine (NEJM), show that both the incidence of treatment failure and need for splenectomy were reduced among the Nplate-treated patients. Data also showed that patients receiving SOC therapies required splenectomies earlier when compared with patients treated with Nplate. Additionally, patients in the Nplate group experienced increased platelet counts, higher platelet response rates, less bleeding, and fewer blood transfusions compared to patients in the SOC group. Adverse events associated with Nplate treatment were similar to those in previous studies, were generally mild or moderate in severity, and did not result in treatment discontinuation. Headache and fatigue were the most commonly reported adverse events.

"This is the first study to compare a variety of ITP treatments and demonstrated that Nplate not only maintained platelet counts more effectively than standard medical treatments, but also reduced overall treatment failure and splenectomies," said Dr. David J. Kuter, head of Hematology, Massachusetts General Hospital, Boston, and lead investigator and study author.

Chronic ITP is a serious autoimmune disorder characterized by low platelet counts in the blood (thrombocytopenia), which can lead to serious bleeding events.

Nplate Study Meets Co-Primary Endpoints

The year-long, open-label study had two co-primary endpoints: the incidence of treatment failure and the incidence of splenectomy.

• Incidence of Treatment Failure: The Nplate group had a significantly lower incidence of treatment failure. Results showed that 11 percent of Nplate patients (18/157) experienced treatment failure compared with 30 percent of SOC patients (23/77) (p=0.001; odds ratio 0.31, 95 percent CI, 0.15-0.61).
• Treatment failures were defined as patients having platelet counts less than or equal to 20,000 platelets per microliter for four consecutive weeks at the highest recommended dose and schedule, a major bleeding event, and/or a change in therapy due to intolerable side effects or bleeding symptoms. Patients who required a splenectomy due to intolerable side effects or bleeding symptoms were also counted as treatment failures.
• Incidence of Splenectomy: Nplate patients had a significantly lower incidence of splenectomy. Nine percent of Nplate patients (14/157) underwent splenectomy compared with 36 percent of patients (28/77) in the SOC group (p<0.001, odds ratio 0.17, 95 percent CI, 0.08-0.35).

Patients were enrolled into the study from North America, Europe, and Australia. Geographical regions had no effect on either incidence of treatment failure or splenectomy.

Nplate Study Meets Secondary Endpoints

Secondary endpoints of the study included time to splenectomy, platelet counts, and platelet response.

• Time to Splenectomy: Patients receiving Nplate experienced a significantly longer time to splenectomy than did SOC-treated patients (p<0.001).
• Platelet Count: The mean platelet count was higher in the Nplate group than the SOC group throughout the treatment period.
• Platelet Response: The platelet response rate (a weekly platelet count greater than 50,000 platelets per microliter) was 2.3 times greater in Nplate-treated patients than in SOC-treated patients (p<0.001).
• Between weeks two and 52, the percentage of patients with a platelet response ranged from 71 percent (108/152) to 92 percent (127/138) in the Nplate group (median platelet count: 108,000 to 176,000 platelets per microliter) and between 26 percent (16/62) and 51 percent (26/51) in the SOC group (median platelet count: 35,000 to 52,000 platelets per microliter).

"For many adult chronic ITP patients, the side effects of some SOC treatments, including splenectomies, are often more debilitating than the disease itself," said Professor Mathias Rummel, head of hematology at the Hospital of the Justus-Liebig University, Giessen, Germany. "Nplate may offer the potential for long-term effective treatment in patients who wish either to avoid or defer a splenectomy."

Nplate Study Shows Favorable Benefit: Risk Profile for Chronic ITP Patients

The safety profile was also comparable between patients receiving Nplate and those receiving SOC according to results from the study.

• Bleeding Events: There was a statistically significant lower exposure-adjusted incidence of overall bleeding events (p=0.001) and lower incidence of bleeding events with a severity grade of three or greater (p=0.02) in patients treated with Nplate compared to the SOC group.
• Blood Transfusions: Forty-one blood transfusions were administered to 8 percent of Nplate patients (12/154) compared to 76 transfusions to 16 percent of SOC patients (12/75).

More than 90 percent of patients in both groups reported at least one adverse event during the treatment period. Headache and fatigue were the most commonly reported adverse events. Fewer patients in the Nplate group experienced a serious adverse event than the SOC group. Serious adverse events occurred in 23 percent (35/154) of patients who received Nplate and 37 percent (28/75) of patients who received SOC. Likewise, treatment-related serious adverse events occurred in fewer Nplate-treated patients (5 percent, 7/154) compared with 8 percent (6/75) of the SOC-treated patients. The most common serious adverse event was thrombocytopenia which occurred in 3 percent (5/154) of Nplate-treated patients and 12 percent (9/75) of SOC-treated patients. Two hematologic malignancies occurred in SOC-treated patients.

About the Study

The open-label study enrolled a total of 234 patients and assessed the efficacy and safety of Nplate compared to SOC treatments for adult patients with chronic ITP. SOC treatments were prescribed by the investigator according to standard institutional practices or therapeutic guidelines; the only treatments not allowed were investigational agents or other thrombopoietic agents. Although not FDA or European Medicines Agency-approved for treatment of chronic ITP, rituximab was allowed as it has compendia listing and is widely regarded as a SOC treatment for chronic ITP. The most commonly used treatments in the SOC arm were: glucocorticoids (63 percent), immunoglobulins (33 percent), rituxumab (20 percent), azathioprine (9 percent), and danazol (7 percent).

About Adult ITP

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 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.

Some other available treatments (e.g., corticosteroids, immunoglobulins) are often unsuitable for long-term use due to tolerability issues and poor predictability of response. Surgical therapy (removal of the spleen) can be an option for many adult patients with chronic ITP, but does not work in all cases, and can be contraindicated in certain cases. Currently, there are approximately 90,000 adult chronic ITP patients in Europe and the United States (U.S.). ITP affects about twice as many adult women as men.  

Nplate is only indicated to treat adult chronic ITP. Nplate is currently under investigation for children ages 12 months to 18 years old with persistent severe thrombocytopenia.

About Nplate

Nplate is the first platelet producer approved in the European Union (EU), Canada, Australia, Russia, Mexico and the U.S. Nplate also has received orphan designation for chronic ITP in the U.S. (2003), the EU (2005), Switzerland (2005), Japan (2006) and Mexico (2010).

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

Nplate was named as a recipient of the U.S. Prix Galien 2009 "Best Biotechnology Product" award and also received the 2009 Scrip Awards for "Best New Drug." Nplate has also been honored with numerous awards throughout the EU, including a 2010 Prix Galien in France in the category of "Drugs for Rare Diseases." Most recently, Nplate was awarded the 2010 International Prix Galien Award for Best Pharmaceutical Research and Development.

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

U.S. Nplate Indication

In the U.S., 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. Nplate should not be used in an attempt to normalize platelet counts.

EU Nplate Indication

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.

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 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^® 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.

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 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.

About Amgen

Amgen discovers, develops, manufactures 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 have 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 deep and broad 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 www.amgen.com.

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