Novartis announced long-term study results supporting the positive safety and efficacy of Promacta (eltrombopag) in adults with chronic/persistent (enrolling patients that were 6 or more months from diagnosis) immune (idiopathic) thrombocytopenia (ITP). The EXTEND study found that a majority of patients maintained a substantial clinical response and many no longer needed concomitant ITP medications. The research evaluated patients for up to 8 years of continuous treatment (median exposure of 2.4 years).
ITP is a rare and potentially serious blood disorder where the blood doesn't clot as it should due to a low number of platelets. As a result, patients with ITP experience bruising, bleeding and, in rare cases, serious hemorrhaging that can be fatal. The goal of treatment in chronic/persistent ITP is to maintain a safe platelet count that reduces the risk of bleeding.
"The EXTEND data published in Blood validate Promacta as an important oral treatment option that, by often increasing platelet counts, significantly decreased bleeding rates and reduced the need for concurrent therapies in certain patients with chronic/persistent immune thrombocytopenia," said lead author James Bussel, M.D., professor emeritus of pediatrics at Weill Cornell Medicine. "With this information, physicians can better optimize long-term disease management for appropriate patients living with this chronic disease."
The efficacy results of EXTEND demonstrated that median platelet counts were elevated to ≥50×109/L within two weeks of Promacta treatment, with median platelet counts >50×109/L maintained for more than four years. Post-baseline, overall bleeding rates declined and the majority of bleeding that occurred during the study was Grade 1 or 2 according to the World Health Organization bleeding scale. Some patients (39%) were capable of reducing or permanently stopping one or more concomitant ITP medications without the need for rescue therapy, many of which sustained reduction for at least 24 weeks.
EXTEND, an open-label extension study of four trials (TRA100773A, TRA100773B, TRA102537/RAISE and TRA108057/REPEAT) of Promacta, enrolled 302 adults with chronic/persistent ITP (6 or more months from diagnosis) who had received prior therapy for their ITP, and is the largest study of its kind. To qualify for the prior trials, patients must have had thrombocytopenia for at least 6 months (chronic ITP was previously defined as thrombocytopenia for 6 or more months).The objectives were to assess the safety and efficacy of long-term treatment with Promacta, including the proportion of patients achieving stable platelet counts during treatment with Promacta; maximum duration of platelet count elevation ≥50×109/L or ≥30×109/L during treatment with Promacta, and the effect of Promacta on reducing and/or sparing concomitant ITP therapies, while maintaining a platelet count ≥50×109/L1.
The study allowed each patient to achieve an individualized dose and schedule of eltrombopag based upon their platelet counts in the desired range between 50 to 200 Gi/L. Therefore, patients who were enrolled in EXTEND must have completed the treatment and follow-up periods as defined in previous protocol and must have not experienced eltrombopag-related toxicity or other drug intolerance on prior eltrombopag study even if resolved. In addition, patients who discontinued from a previous study due to toxicity were not eligible unless they received placebo.
Promacta was started at a dose of 50 mg/day and titrated to 25-75 mg/day or less often based on platelet counts. Maintenance dosing continued after minimization of concomitant ITP medication and optimization of Promacta dosing. The overall median duration of exposure was 2.37 years (range, 2 days to 8.76 years) and mean average daily dose was 50. (range, 1–75) mg/day. One hundred thirty five adult patients (45%) completed the study and 75 adult patients (25%) were treated for four or more years. Most patients were aged <65 years, female, and had platelet counts <30×109/L at baseline. About one-third were using concomitant medications at baseline, and 53% had received three or more prior ITP therapies. In addition, 91% (276/302) of patients achieved platelet counts ≥30×109/L without rescue treatment, and 86% (259/302) achieved platelet counts ≥50×109/L without rescue treatment.
Grade 3 and 4 adverse events (AEs) occurred in 26% and 6% of patients, respectively. Grade 3 cataracts occurred in four (1%) patients and Grade 3 pain in extremity in six (2%) patients. Grade 3 AEs occurring in three (<1%) patients each included diarrhea, headache, migraine, dyspnea, decreased platelet count, and menorrhagia; those occurring in five (2%) patients each included pneumonia, fatigue, back pain, increased alanine aminotransferase, increased aspartate aminotransferase, anemia, and hypertension. Grade 4 anemia and thrombocytopenia occurred in three (<1%) and four (1%) patients, respectively. All other Grade 4 events occurred in one patient each.
Chronic/persistent ITP is a rare and potentially serious blood disorder that is characterized by the improper functioning or destruction of platelets, which are blood cells that allow the blood to clot properly3. People who have ITP often have purple bruises or tiny red or purple dots on the skin. They also display symptoms such as nosebleeds, bleeding from the gums during dental work, or other bleeding that is hard to stop. The potential for drops in platelet counts may also cause emotional distress and may result in a hindered ability to do work or embarrassment due to visible symptoms.
ITP is classified by duration from diagnosis into: acute (0-3 months), persistent (3-12 months duration) and chronic (>12 months duration). Chronic/persistent ITP is more likely to occur in adults, and women are affected two to three times more often than men.
The goal of treatment in chronic/persistent ITP is to maintain a safe platelet count that reduces the risk of bleeding. Treatment is determined by the severity of the symptoms. In most cases, drugs that alter the immune system's attack on the platelets are prescribed to help manage bleeding and bruising in adults.
Eltrombopag, marketed as Promacta in the United States and Revolade in countries outside the US, is approved in more than 100 countries worldwide for the treatment of thrombocytopenia in adult patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an inadequate response or are intolerant to other treatments, approved in over 45 countries worldwide for the treatment of patients with severe aplastic anemia (SAA) who are refractory to other treatments, and also approved in more than 50 countries for the treatment of thrombocytopenia in patients with chronic hepatitis C to allow them to initiate and maintain interferon-based therapy. Eltrombopag is approved in the US and in the European Union for the treatment of thrombocytopenia in pediatric patients 1 year and older with chronic immune (idiopathic) thrombocytopenia (ITP) who have had an insufficient response to corticosteroids and immunoglobulins.