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Ligand Pharmaceuticals: FDA to OK GlaxoSmithKline Promacta/Revolade [Health & Beauty Close - Up](Health & Beauty Close - Up Via Acquire Media NewsEdge) Ligand Pharmaceuticals reported that its partner GlaxoSmithKline has received approval of a supplemental New Drug Application for the once-daily use of Promacta/Revolade in patients with severe aplastic anemia who have had an insufficient response to immunosuppressive therapy. In a release, the Company noted the approval by the FDA is based on results from an investigator-sponsored Phase II study (09-H- 0154) conducted by the National Heart, Lung and Blood Institute at the National Institutes of Health. The study demonstrated a hematologic response in SAA patients treated with eltrombopag who had an insufficient response to IST: -Forty percent (95 percent CI, 25, 56) of patients (N=17) experienced a hematologic response in at least one lineage - platelets, red blood cells, or white blood cells - after Week 12. -In the extension phase, eight patients achieved a multi-lineage response; four of these patients subsequently tapered off treatment and maintained the response (median follow up 8.1 months, range 7.2- 10.6 months). -Ninety-one percent of patients were platelet transfusion- dependent at baseline; the platelet transfusion-free period in responders ranged from eight to 1,096 days (median 200 days). -Eighty-six percent of patients were RBC-transfusion dependent at baseline; the RBC transfusion-free period in responders ranged from 15 to 1,082 days (median 208 days). The most common adverse reactions in the single-arm, open-label trial, in 43 patients with SAA who received Promacta were: nausea (33 percent), fatigue (28 percent), cough (23 percent), diarrhea (21 percent), and headache (21 percent). In this trial, patients had bone marrow aspirates evaluated for cytogenetic abnormalities. Eight patients had a new cytogenetic abnormality reported, including five patients who had complex changes in chromosome 7. If new cytogenetic abnormalities are observed, discontinuation of Promacta should be considered. Eltrombopag was administered at an initial dose of 50 mg once daily for two weeks and increased over two-week periods up to a maximum dose of 150 mg once daily. The primary endpoint was hematologic response which was initially assessed after 12 weeks of treatment with eltrombopag. Treatment was discontinued after 16 weeks if no hematologic response was observed. Additional efficacy assessments included median duration of response in months. Eltrombopag is marketed under the brand name Promacta in the U.S. and Revolade in most ex-U.S. countries. In addition to the approval of Promacta for SAA in the U.S., eltrombopag is indicated for the treatment of thrombocytopenia in patients with: -chronic immune thrombocytopenia who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy. -Promacta should be used only in patients with ITP whose degree of thrombocytopenia and clinical condition increase the risk for bleeding. -chronic hepatitis C to allow the initiation and maintenance of interferon-based therapy. -Promacta should be used only in patients with chronic hepatitis C whose degree of thrombocytopenia prevents the initiation of interferon-based therapy or limits the ability to maintain interferon-based therapy. -Safety and efficacy have not been established in combination with direct acting antiviral agents used without interferon for treatment of chronic hepatitis C. Important Safety Information1 Warning: Risk For Hepatic Decompensation in Patients With Chronic Hepatitis C In patients with chronic hepatitis C, Promacta in combination with interferon and ribavirin may increase the risk of hepatic decompensation. (See Section 5.1 of the full Prescribing Information for additional information). Hepatotoxicity: Promacta can cause liver enzyme elevation, therefore, monitoring of liver function before and during therapy is required. If abnormalities are confirmed, monitoring of serum liver tests should continue until resolved or stabilized. Promacta should be discontinued if abnormalities are progressively increasing, persistent, or accompanied by clinical symptoms of liver injury or evidence for hepatic decompensation. Hepatotoxicity may reoccur if Promacta is reinitiated. Thrombotic/Thromboembolic Complications: Thrombotic/thromboembolic complications may result from increases in platelet counts with Promacta. Reported thrombotic/ thromboembolic complications included both venous and arterial events and were observed at low and normal platelet counts. The potential for an increased risk of thromboembolism when administering Promacta to patients with known risk factors for thromboembolism should be considered. To minimize the risk for thrombotic/thromboembolic complications, Promacta should not be used in an attempt to normalize platelet counts. Follow the dose adjustment guidelines to achieve and maintain target platelet counts. Cataracts: Cataracts have been reported in patients taking Promacta. A baseline ocular examination should be performed prior to administration of Promacta. During therapy with Promacta, regularly monitoring of patients for signs and symptoms of cataracts is required. Drug Interactions: Promacta must not be taken within four 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 a single-arm, open-label trial in 43 patients with SAA who received Promacta were: nausea (33 percent), fatigue (28 percent), cough (23 percent), diarrhea (21 percent), and headache (21 percent). In this trial, patients had bone marrow aspirates evaluated for cytogenetic abnormalities. Eight patients had a new cytogenetic abnormality reported, including five patients who had complex changes in chromosome 7. If new cytogenetic abnormalities are observed, discontinuation of Promacta should be considered. The most common adverse reactions in three placebo-controlled clinical trials in chronic ITP patients for Promacta versus placebo were: nausea (9 percent vs. 3 percent), diarrhea (9 percent vs. 7 percent), upper respiratory tract infection (7 percent vs. 6 percent), vomiting (6 percent vs. <1 percent), increased alanine aminotransferase (ALT) (5 percent vs. 3 percent), myalgia (5 percent vs. 2 percent), urinary tract infection (5 percent vs. 3 percent), oropharyngeal pain (4 percent vs. 3 percent), increased aspartate aminotransferase (4 percent vs. 2 percent), pharyngitis (4 percent vs. 2 percent), back pain (3 percent vs. 2 percent), influenza (3 percent vs. 2 percent), paresthesia (3 percent vs. 2 percent), and rash (3 percent vs. 2 percent). The most common adverse reactions in two randomized, placebo- controlled clinical trials in thrombocytopenic patients with chronic hepatitis C for Promacta versus placebo were: anemia (40 percent vs. 35 percent), pyrexia (30 percent vs. 24 percent), fatigue (28 percent vs. 23 percent), headache (21 percent vs. 20 percent), nausea (19 percent vs. 14 percent), diarrhea (19 percent vs. 11 percent), decreased appetite (18 percent vs. 14 percent), influenza- like illness (18 percent vs. 16 percent), asthenia (16 percent vs. 13 percent), insomnia (16 percent vs. 15 percent), cough (15 percent vs. 12 percent), pruritus (15 percent vs. 13 percent), chills (14 percent vs. 9 percent), myalgia (12 percent vs. 10 percent), alopecia (10 percent vs. 6 percent), and peripheral edema (10 percent vs. 5 percent). Prior to the revised label being posted online, a copy of the label may be requested from GSK Media or Investor Relations. More information: gsk.com ((Comments on this story may be sent to [email protected])) (c) 2014 ProQuest Information and Learning Company; All Rights Reserved. |