GSK announces results of Phase III PETIT2 study of eltrombopag (Promacta™/Revolade™) in paediatric patients with chronic immune thrombocytopenia

GSK announces results of Phase III PETIT2 study of eltrombopag (Promacta™/Revolade™) in paediatric patients with chronic immune thrombocytopenia

GlaxoSmithKline (GSK) plc today announced the results from the Phase III PETIT2 study evaluating the efficacy of eltrombopag vs. placebo in paediatric patients with chronic immune (idiopathic) thrombocytopenic purpura (cITP). Eltrombopag—marketed as Promacta in the U.S. and as Revolade in Europe and other countries across the world—met its primary endpoint, achieving a statistically significant improvement in platelet counts with almost 40 percent of patients treated with eltrombopag attaining a consistent platelet response for 6 of 8 weeks compared to placebo (39.7 percent vs. 3.4 percent, respectively, p<0.001).

The PETIT2 study results were highlighted today as part of a Press Briefing and Oral Presentation at the European Haematology Association Annual Congress, 12–15 June in Milan, Italy.

"The PETIT2 study results presented today show an increase in platelet response rate with eltrombopag treatment— an important result given that these children had failed other standard therapies," said Dr. Rafael Amado, Head of Oncology R&D, GlaxoSmithKline. "We look forward to continuing to assess the potential of eltrombopag in these patients and to moving forward with planned regulatory submissions for a paediatric indication in cITP later this year." 

Efficacy results for PETIT2 were consistent across age cohorts. The safety profile was consistent with the established profile for eltrombopag and no new safety concerns were observed. The most common adverse events (AEs) occurring most frequently in the eltrombopag arm included nasopharyngitis, rhinitis, cough and respiratory tract infection. Grade 3/4 AEs occurred in 12.7 percent of patients treated with eltrombopag and 10.3 percent of patients in the placebo group. Serious AEs were reported in 8 percent of eltrombopag-treated patients vs. 14 percent in the placebo arm.

Additional results from an early phase study of eltrombopag in previously treated paediatric patients with cITP were also presented at this meeting.

About cITP

Immune (idiopathic) thrombocytopenic purpura (ITP)—characterised by a low platelet count—affects as many as 5 in 100,000 children each year.[1] While many children with ITP do not require treatment and/or their disease resolves, up to 30 percent of patients experience persistent disease at 12 months and are diagnosed with cITP.[2],[3],[4] Patients with paediatric cITP are at a high risk of severe bleeding.

About PETIT2

PETIT2 (TRA115450) was 2-part, double-blind, randomised placebo-controlled and open-label study to investigate the efficacy, safety and tolerability of eltrombopag in paediatric patients with previously treated cITP. The multi-centre study enrolled 93 subjects at 38 centres in 14 countries.

The primary objective of the study was to assess the efficacy of eltrombopag, relative to placebo, in achieving platelet counts of ≥50 Gi/L among paediatric patients with previously treated cITP for at least 12 months. The initial phase of the study compared eltrombopag to placebo for 13 weeks. All study participants were then treated with eltrombopag in the second phase of the study (through to week 24).

About Eltrombopag (Promacta™/Revolade™)

Eltrombopag is not approved or licensed anywhere in the world for use in chronic immune (idiopathic) thrombocytopenic purpura in the paediatric setting.

For full US Prescribing Information for Promacta® (eltrombopag), including Boxed Warning, please visit: https://www.gsksource.com/gskprm/htdocs/documents/PROMACTA-PI-MG-COMBINED.PDF. For the European Union (EU) Summary of Product Characteristics (SPC) for Revolade® (eltrombopag) in approved indications, please visit http://health.gsk.com/.  

Promactaand Revoladeare trademarks of the GSK group of companies.

Important Safety Information for Eltrombopag

WARNING: RISK FOR HEPATIC DECOMPENSATION IN PATIENTS WITH CHRONIC HEPATITIS C

In patients with chronic hepatitis C, eltrombopag in combination with interferon and ribavirin may increase the risk of hepatic decompensation.

Hepatotoxicity:

Eltrombopag can cause liver enzyme elevations.  Measure serum ALT, AST, and bilirubin prior to initiation of eltrombopag, every 2 weeks during the dose adjustment phase, and monthly following establishment of a stable dose. Eltrombopag inhibits UGT1A1 and OATP1B1, which may lead to indirect hyperbilirubinemia.  If bilirubin is elevated, perform fractionation. Evaluate abnormal serum liver tests with repeat testing within 3 to 5 days. If the abnormalities are confirmed, monitor serum liver tests weekly until resolved or stabilized.

Discontinue eltrombopag if ALT levels increase to ≥3X upper limit of normal (ULN) in patients with normal liver function or ³3X baseline in patients with pre-treatment elevations in transaminases and are: progressively increasing; or persistent for ≥4 weeks; or accompanied by increased direct bilirubin; or accompanied by clinical symptoms of liver injury or evidence for hepatic decompensation.

If the potential benefit for reinitiating treatment with eltrombopag is considered to outweigh the risk for hepatotoxicity, then consider cautiously reintroducing eltrombopag and measure serum liver tests weekly during the dose adjustment phase. Hepatotoxicity may reoccur if eltrombopag is reinitiated. If liver tests abnormalities persist, worsen or recur, then permanently discontinue eltrombopag.

Thrombotic/Thromboembolic Complications:

Thrombotic/thromboembolic complications may result from increases in platelet counts with eltrombopag. Reported thrombotic/thromboembolic complications included both venous and arterial events and were observed at low and at normal platelet counts. Consider the potential for an increased risk of thromboembolism when administering eltrombopag to patients with known risk factors for thromboembolism. To minimize the risk for thrombotic/thromboembolic complications, do not use eltrombopag in an attempt to normalize platelet counts. Follow the dose adjustment guidelines to achieve and maintain target platelet counts.

Cataracts:

In the 3 controlled clinical trials in chronic ITP, cataracts developed or worsened in 15 (7%) patients who received 50 mg eltrombopag daily and 8 (7%) placebo-group patients. In the extension trial, cataracts developed or worsened in 4% of patients who underwent ocular examination prior to therapy with eltrombopag.

Cataracts were observed in toxicology studies of eltrombopag in rodents. Perform a baseline ocular examination prior to administration of eltrombopag and, during therapy with eltrombopag, regularly monitor patients for signs and symptoms of cataracts.

Laboratory Monitoring:

In patients with chronic ITP, monitor serum liver tests (see Hepatotoxicity section). During therapy with eltrombopag, assess complete blood counts (CBCs) with differentials, including platelet counts, weekly until a stable platelet count has been achieved. Monitor platelet counts monthly thereafter.  Obtain CBCs with differentials, including platelet counts, weekly for at least 4 weeks following discontinuation of eltrombopag.

Drug Interactions:

Eltrombopag must not be taken within 4 hours of any medications or products containing polyvalent cations such as antacids, dairy products, and mineral supplements.

Adverse Reactions:

The most common adverse reactions in 3 placebo-controlled clinical trials in chronic ITP patients (≥3% and greater than placebo) for eltrombopag versus placebo were: nausea (9% vs. 3%), diarrhoea (9% vs. 7%), upper respiratory tract infection (7% vs. 6%), vomiting (6% vs. <1%), increased ALT (5% vs. 3%), myalgia (5% vs. 2%), urinary tract infection (5% vs. 3%), oropharyngeal pain (4% vs. 3%), increased AST (4% vs. 2%), pharyngitis (4% vs. 2%), back pain (3% vs. 2%), influenza (3% vs. 2%), paresthesia (3% vs. 2%), and  rash (3% vs. 2%).

GSK – one of the world's leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer.  For further information please visit www.gsk.com.

 
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Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D 'Risk factors' in the company's Annual Report on Form 20-F for 2013.
 
References
 
[1]   Terrell DR, Beebe LA, Vesely SK, Neas BR, Segal JB, George JN.Am J Hematol. 2010 Mar;85(3):174-80. doi: 10.1002/ajh.21616.
 
[2]   El-Bostany E, El-Ghoroury E, and El-Ghafar E. Anti-Beta 2 Glycoprotein I in childhood immune thrombocytopenic purpura. Blood Coagulation and Fibrinolysis. 2008;19(1):26-31.
 
[3]   BCSH, (British Committee for Standards in Haematology). Guidelines for the investigation and management of idiopathic thrombocytopenic purpura in adults, children and in pregnancy. Br J Haematol. 2003;120:574-596.
 
[4]   Walker R.W., Walker W. Idiopathic thrombocytopenia, initial illness and long term follow up. Archives of Disease in Childhood. 1984;59:316-322.

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