FDA Approves Nplate® (Romiplostim) For Use In Pediatric Patients With Immune Thrombocytopenia

Application Granted Priority Review Designation

Approval Based on Results That Demonstrated Nplate Successfully Increased and Sustained Platelet Counts in Children Affected by Rare Blood Disorder

News provided by

Amgen

Dec 14, 2018, 16:00 ET

THOUSAND OAKS, Calif., Dec. 14, 2018 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental Biologics License Application (sBLA) for Nplate^® (romiplostim) for the treatment of pediatric patients one year of age and older with immune thrombocytopenia (ITP) for at least six months who have had an insufficient response to corticosteroids, immunoglobulins or splenectomy.

"Today's approval underscores our long-standing commitment to making a positive impact on the lives of patients with rare and difficult-to-treat hematological disorders," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "In the 10 years since the FDA approved Nplate as the first platelet booster for adult patients with chronic ITP, it has made a difference in the lives of thousands of adults, and we're proud to bring this treatment option to children who need it most."

The approval was based on two placebo-controlled studies – Phase 3 and Phase 1/2 – evaluating the safety and efficacy of Nplate in pediatric patients. In the Phase 3 study, published in The Lancet, rates of overall platelet response were increased with the Nplate group (71 percent) compared with placebo (20 percent), p<0.05. Additionally, durable platelet response occurred more frequently with Nplate (52 percent) compared with placebo (10 percent), p<0.05. In the two placebo-controlled trials, adverse reactions with an incidence of > 25 percent in the Nplate arm were contusion, upper respiratory tract infection and oropharyngeal pain.

"Children with ITP are at risk for serious bleeding events and spontaneous bruising due to low platelet counts, which can be worrying for these young patients and their parents. Currently, these patients have a limited number of treatment options, especially for those with refractory disease," said Michael D. Tarantino, M.D., president of the Bleeding and Clotting Disorders Institute and professor of Pediatrics and Medicine, University of Illinois College of Medicine-Peoria, Peoria, Ill. "Today's approval of Nplate offers new hope to the pediatric ITP community as it provides children with a new treatment option that may help to maintain safe platelet counts."

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 prevalence of ITP in children is 5.3 per 100,000 children annually.¹The treatment goal for children with ITP is to achieve and maintain a platelet count that reduces the risk of bleeding.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 chronic immune thrombocytopenia (ITP).³ In the U.S. and European Union, 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 67 countries, including Canada, Australia and Japan.

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

Important U.S. Nplate^® Safety Information

Risk of Progression of Myelodysplastic Syndromes to Acute Myelogenous Leukemia

In Nplate^® clinical trials of adult 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 chronic 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. Headaches were usually of mild or moderate severity.
Most common adverse reactions in adults (≥ 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%).

Pediatric ITP

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%).
Most common adverse reactions (≥ 5% incidence and > 5% more frequent 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%).
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.
Women who become pregnant during Nplate^® treatment are encouraged to enroll in Amgen's Pregnancy Surveillance Program. Patients or their physicians should call 1-800‑77‑AMGEN (1-800‑772‑6436) to enroll.

Please see full U.S. Prescribing Information and Medication Guide at www.Nplate.com.

About Amgen
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.

Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.

For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.

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