Lintuzumab
Lintuzumab (SGN-33) is a humanized monoclonal antibody used in the treatment of cancer. The drug had been developed by Seattle Genetics as a treatment for acute myeloid leukemia (AML), a condition which results in the deaths of 9,000 people a year in the United States. Lintuzumab targets the CD33 protein, which is expressed in AML and other myeloproliferative diseases, but does not appear in abundance on normal cells.
| Monoclonal antibody | |
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| Type | Whole antibody |
| Source | Humanized (from mouse) |
| Target | CD33 |
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Trials for AML were abandoned in 2010 when a phase IIb trial failed to show increased survival.
As of 2010, Seattle Genetics was conducting Phase II trials of lintuzumab in conjunction with bortezomib (marketed as Velcade) as a treatment for those with myelodysplastic syndromes.[1]
History of AML trials
Lintuzumab had been in mid-stage clinical trial when Seattle Genetics pulled the drug in September 2010 after evidence showed that it did not lead to higher survival rates.[2] The U.S. Food and Drug Administration and the European Medicines Agency had granted lintuzumab orphan drug status for treatment of AML and myelodysplastic syndromes.[1] Seattle Genetics had licensed lintuzumab from PDL BioPharma, which had been unsuccessful in treating AML in clinical trials of its own in which they used lower doses.[2]
The Phase IIb randomized, double-blind clinical trial studied 211 individuals ages 60 and over who had been enrolled by February 2009 and who were poor candidates for high-dose chemotherapy or had made the choice to reject the traditional chemotherapy treatment.[3] The study participants typically had a projected four to five months to live, with half treated with lintuzumab and a low dose of the chemotherapeutic agent cytarabine, while the other half were given cytarabine in combination with a placebo. No patients were harmed in the trial and patients in both groups lived longer than expected, with those being given lintuzumab having a lower death rate. However, the study found that there was no benefit to patients on a statistical basis, and that it did not reduce the risk of infection or the need for blood transfusions.[2]
Competition
Gemtuzumab ozogamicin (marketed as Mylotarg), a similar drug from Pfizer that also targets the CD33 protein on leukemic cells, was withdrawn from the market in June 2010 after trials showed little benefit to patients.
Clofarabine, a treatment for AML marketed by Genzyme as Clolar that targets a different treatment approach, failed to get approval from the FDA in October 2009, which said that additional trials were needed.[2]
References
- Lintuzumab (SGN-33), Seattle Genetics. Accessed September 13, 2010.
- Pollack A (September 13, 2010). "Leukemia Drug Trial Fails". The New York Times.
- Staff (September 13, 2010). "Disappointing Phase II Data Leads Seattle to Ditch AML Candidate". Genetic Engineering & Biotechnology News.
Sources
- Feldman EJ, Brandwein J, Stone R, Kalaycio M, Moore J, O'Connor J, et al. (June 2005). "Phase III randomized multicenter study of a humanized anti-CD33 monoclonal antibody, lintuzumab, in combination with chemotherapy, versus chemotherapy alone in patients with refractory or first-relapsed acute myeloid leukemia". Journal of Clinical Oncology. 23 (18): 4110–6. doi:10.1200/JCO.2005.09.133. PMID 15961759.