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GSK launches new Phase III trials of Revolade, new drug that boosts platelet counts in patients with HCV
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06 November 2007
www.pharmatimes.com
UK drug giant GlaxoSmithKline has kicked off two parallel late-stage trials assessing the potential use of its investigational compound Revolade (eltrombopag; US tradename Promacta) to boost blood platelet counts in patients with hepatitis C.
The drug is an oral, non-peptide thrombopoietin receptor agonist that works by stimulating the production of bone marrow cells that give rise to blood platelets, and is therefore considered a platelet growth factor, says GSK.
According to the World Health Organisation, about 180 million people are infected with hepatitis C globally. Thrombocytopenia (low platelet count) is a common symptom, but because treatment with interferon - which is crucial to controlling the disease - can also reduce platelet levels, patients with this complication can be excluded from starting or being continued on treatment, leading to quicker progression of the illness.
The new Phase III trials - ENABLE 1 and 2 - are designed to investigate whether Revolade can raise platelet counts enough to allow patients with hepatitis C-associated thrombocytopenia to start and maintain treatment with antiviral therapy. The drug's success will be measured by the number of patients who are able to achieve a sustained virological response, ie. an undetectable viral load of hepatitis C for a period of six months after therapy.
"ENABLE will investigate the effect of eltrombopag over a 12-month treatment period to determine how it may help patients to achieve SVR, which in clinical terms is considered a cure for hepatitis C, as well as better understand any related toxicities or tolerability issues," explained John McHutchison, MD, Professor of Medicine and Associate Director, Duke Clinical Research Institute, Durham, North Carolina, US.
Nearing approval?
Revolade is yet to receive its first regulatory approval for any market, but it could soon be available in the UK if a European green light is issued. Just a few days ago, the National Institute for Health and Clinical Excellence said it was assessing the cost-effectiveness of the drug for treating the low platelet count disorder refractory chronic idiopathic thrombocytopenic purpura under its accelerated approval process.
Earlier this year, results from a pivotal international Phase III study showed that Revolade at 50mg-75mg once daily resulted in a statistically significant increase in platelet counts and also reduced bleeding in adult patients with chronic idiopathic thrombocytopenia purpura, and analysts are already hailing the drug as a potential blockbuster for GSK.
GSK drug gets hep C patients onto therapy
30 October 2006
GlaxoSmithKline's platelet-boosting drug Promacta can be an effective treatment for patients with hepatitis C whose low blood platelet counts mean that they cannot be treated with interferon, the standard therapy for the infection.
The results of a Phase II study involving 74 patients with chronic hepatitis C revealed that Promacta (eltrombopag) was able to boost platelet levels in more than 95% of patients treated to the extent that therapy with pegylated interferon alpha could be started.
Low platelet counts - or thrombocytopenia - is a common symptoms in patients with chronic liver disease such as HCV. Because treatment with interferon can also reduce platelet levels, patients with thrombocytopenia can be excluded from starting or being continued on treatment.
Paolo Paoletti, senior vice president of oncology drug development at GSK, said: "As we move into Phase III trials for eltrombopag in a variety of conditions where thrombocytopenia is a complicating factor, these data represent a significant milestone for GSK in supportive care." Phase III trials in this indication are due to start next year.
A Phase II trial of the drug in patients with thrombocytopenia caused by chemotherapy failed in its primary endpoint, although this was due to the chemotherapy drug in the study not significantly impacting platelet production in the first place, which was an unexpected result.
Progress in first indication
Eltrombopag is currently in Phase III trials for the haematological disorder idiopathic thrombocytopenic purpura, and GSK is hoping to file for marketing approval of the drug for short-term treatment of ITP in 2007. It had earlier said it wanted to file later this year, but now says it needs discussion with regulatory authorities "to determine whether these data will be sufficient to file for approval next year."
A phase III clinical programme is underway to assess the use of Promacta for the long-term treatment of ITP, with filings for this indication anticipated in 2008.
Phase III data looks promising for GSK's eltrombopag
11 June 2007
GlaxoSmithKline has presented positive data from a late-stage study of its new platelet-boosting treatment Revolade, one of the drugs in the firm's pipeline that analysts believe can be a blockbuster.
Results from a pivotal international Phase III study, which were presented at the European Haematology Association congress in Vienna, showed that Revolade (eltrombopag), at 50-75mg once daily, resulted in a statistically significant increase in platelet counts and also reduced bleeding in adult patients with chronic idiopathic thrombocytopenia purpura.
ITP is a low platelet count disorder that leaves sufferers at risk of spontaneous bruising, mucosal bleeding and, in severe cases, intracranial haemorrhage. There are estimated to be 50,000-100,000 people diagnosed with chronic ITP in the USA alone and the predicted five-year mortality rates for ITP patients with persistent low platelet counts range from 2.2% for patients younger than 40 years of age, to 47.8% for those older than 60.
Patients on the trial were randomised to either placebo (38 patients) or eltrombopag 50mg (76 patients) once daily for six weeks though the Revolade dose could be increased to 75mg in patients not responding after an initial three weeks of treatment. At the end of the trial, 59% of eltrombopag-treated patients and 16% on placebo treated patients achieved a platelet count of more than 50,000/microlitre. Importantly, said GSK, there was a significantly lower incidence of bleeding events during treatment with Revolade compared to placebo.
Drew Provan of the Department of Haematology at the Royal London Hospital, UK, and an investigator on the trial said that options are particularly limited for those patients who fail to respond to primary treatment altogether and those who initially respond and then fail. Now, he added, "these trial results demonstrate that eltrombopag may represent the potential for a new oral therapy to reduce the number of bleeding episodes in ITP patients."
Revolade, which will be marketed as Promacta in the USA if approved, was discovered as a result of research collaboration between GSK and Ligand Pharmaceuticals, and several trials of the compound are ongoing.
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