Lintuzumab
Encyclopedia
Lintuzumab is a humanize
d 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 disease
s, but does not appear in abundance on normal cells.
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 syndrome
s.
and the European Medicines Agency
had granted lintuzumab orphan drug
status for treatment of AML and myelodysplastic syndrome
s.
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. Lintuzumab would have been the first medication on the market for the treatment of acute myeloid leukemia, a condition that strikes 12,000 Americans each year, in which the body produces excessive numbers of abnormal white blood cells that accumulate in bone marrow
and interfere with the production of normal blood cells. AML is the most common form of acute leukemia
affecting adults, and its incidence increases with age. More than half of those afflicted with AML are elderly and are unable to withstand the traditional chemotherapy
approach.
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. The study participants typically had a projected four to five months to live, with half treated with lintuzumab and a low dose of the chemotheraputic 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 transfusion
s.
(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.
Humanize
Humanize may refer to:*Humanize a 2001 album by the British jazz/funk band Big Boss Man*Humanized antibody, a type of monoclonal antibody...
d monoclonal antibody used in the treatment of cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
. The drug had been developed by Seattle Genetics as a treatment for acute myeloid leukemia
Acute myeloid leukemia
Acute myeloid leukemia , also known as acute myelogenous leukemia, is a cancer of the myeloid line of blood cells, characterized by the rapid growth of abnormal white blood cells that accumulate in the bone marrow and interfere with the production of normal blood cells. AML is the most common acute...
(AML), a condition which results in the deaths of 9,000 people a year in the United States. Lintuzumab targets the CD33
CD33
CD33 or Siglec-3 is a transmembrane receptor expressed on cells of myeloid lineage. It is usually considered myeloid-specific, but it can also be found on some lymphoid cells.It binds sialic acids, therefore is a member of the SIGLEC family of lectins....
protein, which is expressed in AML and other myeloproliferative disease
Myeloproliferative disease
The myeloproliferative diseases are a group of diseases of the bone marrow in which excess cells are produced. They are related to, and may evolve into, myelodysplastic syndrome and acute myeloid leukemia, although the myeloproliferative diseases on the whole have a much better prognosis than...
s, but does not appear in abundance on normal cells.
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
Bortezomib
Bortezomib is the first therapeutic proteasome inhibitor to be tested in humans. It is approved in the U.S. for treating relapsed multiple myeloma and mantle cell lymphoma...
(marketed as Velcade) as a treatment for those with myelodysplastic syndrome
Myelodysplastic syndrome
The myelodysplastic syndromes are a diverse collection of hematological medical conditions that involve ineffective production of the myeloid class of blood cells....
s.
History of AML trials
Lintuzumab had been in mid-stage clinical trial when the manufacturer pulled the drug in September 2010 after evidence showed that it did not lead to higher survival rates. The U.S. Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
and the European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
had granted lintuzumab orphan drug
Orphan drug
An orphan drug is a pharmaceutical agent that has been developed specifically to treat a rare medical condition, the condition itself being referred to as an orphan disease...
status for treatment of AML and myelodysplastic syndrome
Myelodysplastic syndrome
The myelodysplastic syndromes are a diverse collection of hematological medical conditions that involve ineffective production of the myeloid class of blood cells....
s.
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. Lintuzumab would have been the first medication on the market for the treatment of acute myeloid leukemia, a condition that strikes 12,000 Americans each year, in which the body produces excessive numbers of abnormal white blood cells that accumulate in bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
and interfere with the production of normal blood cells. AML is the most common form of acute leukemia
Acute leukemia
Acute leukemia or acute leukaemia is a generic term used to describe a family of serious medical conditions relating to an original diagnosis of leukemia...
affecting adults, and its incidence increases with age. More than half of those afflicted with AML are elderly and are unable to withstand the traditional chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
approach.
The Phase IIb randomized, double-blind clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...
studied 211 individuals ages 60 and over who had been enrolled by February 2009 and who were poor candidates for high-dose chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....
or had made the choice to reject the traditional chemotherapy treatment. The study participants typically had a projected four to five months to live, with half treated with lintuzumab and a low dose of the chemotheraputic agent cytarabine
Cytarabine
Cytarabine, or cytosine arabinoside, is a chemotherapy agent used mainly in the treatment of cancers of white blood cells such as acute myeloid leukemia and non-Hodgkin lymphoma. It is also known as Ara-C...
, while the other half were given cytarabine in combination with a placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
. 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 transfusion
Blood transfusion
Blood transfusion is the process of receiving blood products into one's circulation intravenously. Transfusions are used in a variety of medical conditions to replace lost components of the blood...
s.
Competition
Gemtuzumab ozogamicinGemtuzumab ozogamicin
Gemtuzumab ozogamicin is a drug-linked monoclonal antibody that was used to treat acute myelogenous leukemia from 2000-2010...
(marketed as Mylotarg), a similar drug from Pfizer
Pfizer
Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...
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
Clofarabine
Clofarabine is a purine nucleoside antimetabolite marketed in the U.S. and Canada as Clolar. In Europe and Australia/New Zealand the product is marketed under the name Evoltra. It is FDA-approved for treating a type of leukaemia called relapsed or refractory acute lymphoblastic leukaemia in...
, a treatment for AML marketed by Genzyme
Genzyme
Genzyme Corporation is a fully owned subsidiary of Sanofi-Aventis. Before its acquisition, Genzyme was an American biotechnology company based in Cambridge, Massachusetts. In 2010, Genzyme was the world’s third-largest biotechnology company, employing more than 11,000 people around the world...
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.