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Current Opinion in Investigational... Oct 2001Genetics Institute has developed and launched oprelvekin (rhIL-11; Neumega), a recombinant form of human IL-11. In November 1997, the FDA cleared oprelvekin for the... (Review)
Review
Genetics Institute has developed and launched oprelvekin (rhIL-11; Neumega), a recombinant form of human IL-11. In November 1997, the FDA cleared oprelvekin for the prevention of severe thrombocytopenia and the reduction of the need for platelet transfusions following myelosuppressive chemotherapy in susceptible patients with non-myeloid malignancies 12703021. The product was launched at the end of 1997 [312556]. By December 1999, phase III trials for Crohn's disease (CD) were underway [363007]. Genetics Institute had commenced a 150-patient phase II trial for mild-to-moderate CD and mucositis and the company planned to file regulatory procedures for the indication of CD in 1999 [271210]. An oral formulation for this indication has been developed. Oprelvekin is also undergoing phase I clinical trials for colitis [396157], phase II clinical trials for rheumatoid arthritis [413835] and clinical trials for psoriasis [299644]. In March 1997, Wyeth-Ayerst became the licensee for Europe, Africa, Latin America and Asia (with the exception of Japan). Genetics Institute holds marketing rights for North America [239273]. In Japan, oprelvekin is being developed by Genetics Institute and Yamanouchi; phase III trials have commenced [295049] and were ongoing in May 2001 [411763]. In April 1996, analysts at Yamaichi estimated launch in 2001 and maximum annual sales of over yen 10 billion [215896]. In January 1998, Morgan Stanley Dean Witter predicted Yamanouchi's share of sales to be yen 1 billion in 2001, rising to yen 2 billion in 2002 [315458]. Sales of oprelvekin were US $34 million for Genetics institute in fiscal 2000 while, in July 2001, Credit Suisse First Boston estimated that this figure will be US $30 million and US $34 million in 2001 and 2002, respectively [416883].
Topics: Animals; Arthritis, Rheumatoid; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Humans; Inflammatory Bowel Diseases; Interleukin-11; Recombinant Proteins; Structure-Activity Relationship; Thrombocytopenia
PubMed: 11890354
DOI: No ID Found -
American Journal of Ophthalmology Feb 2005To report a case of bilateral optic disk edema in a patient taking oprelvekin for radioimmunotherapy-induced thrombocytopenia.
PURPOSE
To report a case of bilateral optic disk edema in a patient taking oprelvekin for radioimmunotherapy-induced thrombocytopenia.
DESIGN
Observational case report.
METHODS
A 38-year-old man with a history of relapsed non-Hodgkins follicular lymphoma complained of bilateral loss of vision following oprelvekin therapy for thrombocytopenia.
RESULTS
Funduscopic examination demonstrated bilateral optic disk edema with exudates inferotemporal to the right nerve. The results of magnetic resonance imaging of the brain and orbits and lumbar puncture were normal. The disk edema resolved with discontinuation of oprelvekin therapy.
CONCLUSIONS
Oprelvekin therapy may be associated with bilateral optic disk edema. This has been shown to be reversible in a primate model.
Topics: Adult; Antineoplastic Agents; Humans; Interleukin-11; Lymphoma, Follicular; Male; Papilledema; Radioimmunotherapy; Recombinant Proteins; Thrombocytopenia
PubMed: 15734010
DOI: 10.1016/j.ajo.2004.07.055 -
BioDrugs : Clinical Immunotherapeutics,... Aug 1998Oprelvekin is a recombinant human interleukin-11. Its predominant haemopoietic activity is stimulation of megakaryocytopoiesis. Oprelvekin is indicated for the...
UNLABELLED
Oprelvekin is a recombinant human interleukin-11. Its predominant haemopoietic activity is stimulation of megakaryocytopoiesis. Oprelvekin is indicated for the prevention of severe thrombocytopenia and the reduction of platelet transfusion requirements following myelosuppressive chemotherapy in patients with nonmyeloid malignancies at high risk of severe thrombocytopenia. It is the first available pharmacological alternative to platelet transfusions for these patients. Oprelvekin stimulates platelet progenitor cells (megakaryoblasts and colony-forming unit megakaryocytes). The drug also increases megakaryocyte size and ploidy. The recommended adult dosage of subcutaneous oprelvekin is 50 microg/kg once daily, administered until the platelet count is >or=50 000/microl after the expected nadir, but for not more than 21 days per chemotherapy cycle. Three placebo-controlled trials involving patients with cancer (mostly breast cancer) undergoing dose-intensive cancer chemotherapy, with or without autologous bone marrow transplantation (n = 75 to 82), have been conducted. Compared with placebo, oprelvekin 50 microg/kg/day was associated with significantly fewer patients requiring platelet transfusions and a trend towards a lower median number of platelet transfusions. There was also at least a trend towards reduced time to platelet recovery in oprelvekin recipients. The efficacy of oprelvekin is unaffected by previous platelet transfusion requirements and/or chemotherapy. To date the drug has not been shown to ameliorate chemotherapy-induced leucopenia or neutropenia or to have effects on time to neutrophil engraftment or red blood cell transfusion requirements in clinical trials. The most common adverse events with this agent (oedema and dyspnoea) are considered attributable to drug-induced fluid retention and increased plasma volume; these events are usually mild to moderate, reversible on drug discontinuation and dose related. Cardiovascular events including atrial arrhythmias are also considered attributable to increased plasma volume.
CONCLUSIONS
Evidence suggests that oprelvekin reduces severe thrombocytopenia, accelerates platelet recovery and reduces the need for platelet transfusions in patients with nonmyeloid malignancies receiving chemotherapy regimens associated with severe thrombocytopenia. If further studies confirm these findings, oprelvekin is likely to be a valuable means of allowing patients to receive their full planned chemotherapy course.
PubMed: 18020592
DOI: 10.2165/00063030-199810020-00006 -
Journal of the American Pharmaceutical... 1999Oprelvekin decreases the need for platelet transfusion in nontransplant patients receiving myelosuppressive chemotherapy. Until pharmacoeconomics studies determine the...
Oprelvekin decreases the need for platelet transfusion in nontransplant patients receiving myelosuppressive chemotherapy. Until pharmacoeconomics studies determine the most cost-effective strategy for use of oprelvekin, it is likely to be used primarily in patients receiving dose-intensive chemotherapy to maintain the high-dose regimen that may provide a survival advantage for the patient with cancer. Additional product information is available at www.ahp.com/products/neumega.htm.
Topics: Antineoplastic Agents; Blood Platelets; Humans; Interleukin-11; Recombinant Proteins; Thrombocytopenia
PubMed: 10533354
DOI: 10.1016/s1086-5802(15)30363-6 -
BioDrugs : Clinical Immunotherapeutics,... Dec 1997Interleukin-11 (IL-11) is a cytokine which interacts with a variety of haemopoietic and non-haemopoietic cell types. Recombinant human IL-11 (rhIL-11; oprelvekin) is...
Interleukin-11 (IL-11) is a cytokine which interacts with a variety of haemopoietic and non-haemopoietic cell types. Recombinant human IL-11 (rhIL-11; oprelvekin) is produced in Escherichia coli and differs from the naturally occurring protein only in the absence of the amino-terminal proline residue. In synergy with other factors, rhIL-11 stimulates the growth of myeloid, erythroid, and megakaryocyte progenitor cells in vitro. In vivo, rhIL-11 is active in mice, rats, dogs, guinea pigs, hamsters and non-human primates, where the principal activity measured was stimulation of megakaryocytopoiesis and thrombopoiesis. rhIL-11 has shown benefit in 2 clinical trials by significantly reducing severe chemotherapy-induced thrombocytopenia. In addition to its thrombopoietic activity, rhIL-11 has also shown activity in models of acute gastrointestinal mucosal damage. rhIL-11 enhanced survival in mice following cytoablative therapy and in a hamster model of chemotherapy-induced oral mucositis, where treatment with rhIL-11 was associated with decreased mucosal damage, accelerated healing and reduced numbers of deaths. rhIL-11 is currently in clinical trials for the treatment of chemotherapy-induced mucositis. In rat models of acute colonic injury and inflammatory bowel disease, rhIL-11 treatment reduced intestinal mucosal damage and alleviated clinical signs. rhIL-11 has direct effects on activated macrophages to reduce the production of pro-inflammatory mediators. In animal models of endotoxaemia, rhIL-11 treatment reduced serum levels of pro-inflammatory cytokines and blocked hypotension. rhIL-11 increased survival in models of Gram-negative sepsis and toxic shock. Based on these studies, rhIL-11 is currently in clinical trials for treatment of Crohn's disease. Other inflammatory conditions are being further evaluated. Mechanistically, rhIL-11 functions at many levels to control inflammation, ameliorate tissue damage and maintain haemostasis in the face of trauma or infection. rhIL-11 has direct effects on hepatocytes, inducing the production of acute phase reactant proteins, haem oxygenase and tissue inhibitor of metalloproteinase-1 (TIMP-1). TIMP-1 expression can also be induced in synoviocytes and chondrocytes by treatment with rhIL-11. rhIL-11 administration has been associated with increased plasma levels of von Willebrand factor and fibrinogen. rhIL-11 treatment potentially offers multiple benefits for cancer chemotherapy patients, such as prevention of thrombocytopenia, gastrointestinal epithelial protection and subsequent reduction of mucositis, and amelioration of inflammatory complications. In addition, rhIL-11 is being evaluated further in the treatment of inflammatory disorders such as inflammatory bowel disease, rheumatoid arthritis and sepsis.
PubMed: 18031104
DOI: 10.2165/00063030-199708060-00002 -
Hematology. American Society of... Dec 2022Chemotherapy-induced thrombocytopenia (CIT) is common, resulting in increased bleeding risk and chemotherapy delays, dose reduction, and treatment discontinuation, which... (Review)
Review
Chemotherapy-induced thrombocytopenia (CIT) is common, resulting in increased bleeding risk and chemotherapy delays, dose reduction, and treatment discontinuation, which can negatively affect oncologic outcomes. The only agent approved by the US Food and Drug Administration to manage CIT (oprelvekin) was voluntarily withdrawn from the market by the manufacturer, leaving few options for patients. Therefore, patients experiencing CIT present a significant clinical challenge in daily practice. The availability of thrombopoietin receptor agonists has led to formal clinical trials describing efficacy in CIT as well as a rather extensive body of published observational data from off-label use in this setting but no formal regulatory indications for CIT to date. The accumulated data, however, have affected National Comprehensive Cancer Network guidelines, which now recommend consideration of TPO-RA clinical trials as well as off-label use of romiplostim. This review article details the evidence to date for the management of CIT with thrombopoietin receptor agonists (TPO-RAs), discussing the efficacy data, the specific circumstances when treatment is warranted (and when it is generally unnecessary), and safety considerations. Specific recommendations regarding patient selection, initiation, dosing, titration, and discontinuation for TPO-RA therapy in CIT are given, based on published data and expert opinion where evidence is lacking.
Topics: Humans; Receptors, Thrombopoietin; Thrombopoietin; Thrombocytopenia; Hemorrhage; Recombinant Fusion Proteins; Antineoplastic Agents; Purpura, Thrombocytopenic, Idiopathic; Hydrazines; Benzoates
PubMed: 36485134
DOI: 10.1182/hematology.2022000374 -
Pediatric Blood & Cancer Dec 2008
Topics: Adult; Analgesics, Opioid; Antineoplastic Agents; Drug Interactions; Female; Humans; Interleukin-11; Kidney Neoplasms; Morphine; Recombinant Proteins; Thrombocytopenia; Wilms Tumor
PubMed: 18698585
DOI: 10.1002/pbc.21719 -
Cancer Jun 2003Previous research has shown oprelvekin (recombinant human interleukin-11 [rhIL-11]) to be effective in reducing the requirements for platelet transfusions after... (Comparative Study)
Comparative Study
BACKGROUND
Previous research has shown oprelvekin (recombinant human interleukin-11 [rhIL-11]) to be effective in reducing the requirements for platelet transfusions after myelosuppressive chemotherapy in patients who have previously experienced thrombocytopenia. The economic consequences of the routine use of this platelet growth factor and the usual standard of platelet transfusions for prophylaxis of severe chemotherapy-induced thrombocytopenia have not been compared.
METHODS
The authors constructed a decision-analytic model to compare the alternatives of rhIL-11 versus usual care using probability, outcome, and cost data from previously published clinical trials and their own institutional sources. They incorporated the costs of platelet transfusions and adverse events from rhIL-11 into the analysis. Quality-of-life outcomes were not considered. The pharmacoeconomic analysis was based on the criterion of cost minimization from the payer's perspective.
RESULTS
The expected cost of the usual care strategy for prophylaxis of severe thrombocytopenia (transfusion when platelets < 20000 microL(-1)) was US dollars 3495 for a 3-week cycle of chemotherapy. The prophylactic rhIL-11 strategy was more expensive, with an expected cost of US dollars 5328 over the same time period. Nonetheless, it was associated with fewer platelet transfusions, avoiding an average of 6.7 U compared with usual care. The savings from avoidance of platelet transfusion and adverse reactions to transfusion from the use of rhIL-11 were not offset by the substantial cost of the pharmaceutical. The greater expected costs from the rhIL-11 strategy were relatively insensitive to the unit price and efficacy of rhIL-11 and the costs of platelet transfusions and monitoring.
CONCLUSIONS
From the payer's perspective, rhIL-11 cannot be considered a cost-saving clinical strategy compared with routine platelet transfusions for patients with severe chemotherapy-induced thrombocytopenia.
Topics: Antineoplastic Agents; Costs and Cost Analysis; Humans; Interleukin-11; Models, Theoretical; Platelet Transfusion; Recombinant Proteins; Thrombocytopenia
PubMed: 12784347
DOI: 10.1002/cncr.11447 -
Biopharmaceutics & Drug Disposition Oct 2004A study in healthy men and women was performed to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of orally administered recombinant... (Clinical Trial)
Clinical Trial
A study in healthy men and women was performed to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of orally administered recombinant human interleukin-11 (oprelvekin) (OAO). Four cohorts of 10 subjects each received 3, 5, 10 or 30 mg (8:2/OAO:placebo ratio), first as a single dose with a 7-day washout period, then 7 consecutive daily doses. Safety was assessed by ongoing evaluation of adverse events (AEs) and laboratory values. PK samples were collected on the first and last day of dose administration. The established effects of subcutaneous oprelvekin on C-reactive protein (CRP, upward arrow), platelet count (upward arrow), fibrinogen (upward arrow) and hemoglobin (downward arrow), were evaluated. PK analysis showed that most subjects (27/34, 79%) had undetectable serum levels of IL-11. PD measures showed no changes from baseline between any OAO group and the placebo group. Orally administered oprelvekin was safe and well tolerated at all doses. A total of five AEs (abdominal pain, diarrhea, headache, rhinitis, grade 3 alanine aminotransferase elevation) were reported across all groups. Evaluations of serum IL-11 levels indicate that OAO is not systemically absorbed at levels above the lower limit of the bioanalytic assay. These data in addition to the lack of effect on PD measures suggest that there is a decreased potential of systemic adverse events with OAO.
Topics: Administration, Oral; Adult; Humans; Interleukin-11; Middle Aged; Recombinant Proteins
PubMed: 15386478
DOI: 10.1002/bdd.415