GlaxoSmithKline announced that the United States Food and Drug Administration (FDA) granted full approval for Promacta (eltrombopag), an oral tablet that can raise platelet counts in patients with the rare blood disorder chronic immune (idiopathic) thrombocytopenic purpura (ITP) who has an insufficient response to corticosteroids, immunoglobulins or splenectomy.

Promacta initially received FDA orphan drug designation in May 2008 and accelerated approval in November 2008 for chronic ITP. The FDA accelerated approval programme offers a pathway to gain provisional marketing approval for therapies that address unmet patient needs. Full approval of the therapy requires completion of post-marketing clinical trials and commitments that verify clinical benefit.

“Full approval of Promacta was based on clinical studies that provide physicians and patients with a broader understanding of its treatment effect and safety profile,” said Steven Stein, MD, VP of Medicines Development, GlaxoSmithKline. “Promacta is a testament to how the FDA accelerated approval programme supports development of therapies that meet unmet patient needs. Patients with limited treatment options gained access to Promacta while GSK conducted clinical studies that yielded additional efficacy and safety data.”

Chronic ITP is a disorder marked by increased platelet destruction and/or inadequate platelet production in the blood, which causes an increased risk of bruising and bleeding. There are estimated to be approximately 60,000 individuals diagnosed with chronic ITP in the US. People with chronic ITP often bleed from small blood vessels causing bruises or nosebleeds.

The major changes in the Prescribing Information (PI) of Promacta are to the Initial Dose Regimen and to the Thrombotic/Thromboembolic complications in the Warnings and Precautions section of the PI. The label also now includes efficacy and safety data from RAISE, a 6-month, randomized double-blind, placebo-controlled study in patients with ITP.

The updated PI also incorporates two-year safety data from an open-label, single-arm extension study in patients with chronic ITP. This study showed that adverse reactions occurred in a pattern similar to those reported in the placebo-controlled studies.

Additional changes to the PI include updates on dose adjustments, risk of hepatotoxicity, bone marrow reticulin formation, thrombotic/thromboembolic complications, recurrence of thrombocytopenia, haematologic malignancies, cataracts, adverse event information, drug interactions, use in specific patient populations (hepatic and renal impairment) and to the pharmacokinetic section.

Promacta may cause hepatotoxicity. Increases in serum aminotransferase levels and bilirubin were observed. Liver chemistries must be measured before the initiation of treatment and regularly during treatment.

Because of the risk of hepatotoxicity, and other risks including bone marrow reticulin and risk for bone marrow fibrosis, thrombotic/thromboembolic complications, recurrence of thrombocytopenia and haemorrhage risk after Promacta cessation, haematologic malignancies and progression of malignancies, and cataracts, Promacta is available only through a restricted distribution programme called Promacta Cares.

PROMACTA is an oral, non-peptide thrombopoietin receptor agonist that has been shown in pre-clinical and clinical research to stimulate the proliferation and differentiation of megakaryocytes, the bone marrow cells that give rise to blood platelets and was discovered as a result of research collaboration between GlaxoSmithKline and Ligand Pharmaceuticals.