Disease Education
CLL is a form of blood cancer caused by an abnormal accumulation of malignant lymphocytes, a type of white blood cells. According to the American Cancer Society, approximately 14,570 Americans will be diagnosed with the disease in 2011 and 4,380 will die from the malignancy. Five-year survival rate for people with CLL is 80%.
Veltuzumab is currently in a Phase I/II study to determine if a subcutaneous dosing schedule can be established in CLL patients. More information on this trial can be accessed at clinicaltrials.gov.
In addition, our previous studies have shown that B lymphocytes in CLL have increased expression of CD74 relative to normal B cells. Because CD74 is a cell surface receptor believed to function as a contributor to immunity as well as a signaling molecule, we have also launched a study using our anti-CD74 antibody, Milatuzumab, as a therapy for CLL.
Colorectal cancer is cancer that starts in either the colon or the rectum. Most cases of colorectal cancer are adenocarcinomas that begin as benign polyps from glands in the lining of the colon and rectum, which slowly develop into cancer. There is no single cause of colon cancer although the risk increases with age, a high fat diet, ulcerative colitis or Crohn’s disease, and a family or personal history of colorectal cancer.
Colorectal cancer remains a leading cause of cancer incidence and mortality worldwide. It is the third most commonly diagnosed cancer in men and the second in women, with over 1.2 million new cases and 608,700 deaths estimated to have occurred in 2008. In the U.S., with estimated 141,210 new cases and 49,380 deaths attributed to colorectal cancer in 2011, the disease ranked 4th by incidence following lung, breast and prostate cancers, and second only to lung cancer in mortality.
Over the past 10 years, there have been important strides that have reduced the mortality of this disease primarily through more widespread screening that can catch the disease early before extensive spread. Treatment depends partly on the stage of the cancer and may include surgery, chemotherapy, radiation therapy and targeted therapy. However, progress, while real, has been modest. When the disease was diagnosed early and the cancer was confined to its primary site, the 5-year relative survival rate reaches 90%. The rate decreases to 69% when the cancer has spread to regional lymph nodes and 12% when it has metastasized. For all stages combined, the 5-year relative survival rate is 65%.
We have initiated the investigation of our second antibody-drug conjugate, labetuzumab-SN-38, in a Phase I study in patients with relapsed or refractory colorectal cancer. Information on this clinical trial can be obtained from clinicaltrials.gov.
Additionally, our first DNL product, TF2, is also in a Phase I clinical trial for pretargeted imaging and therapy of colorectal cancer. Please visit clinicaltrials.gov.
According to the National Cancer Institute, approximately 454,378 Americans who were alive on January 1, 2008, had non-Hodgkin's lymphoma (NHL). An estimated 66,360 new cases will be diagnosed in 2011 and about 19,320 people will die from the cancer this year. Diffuse large B-cell lymphoma is an aggressive subtype of NHL, which makes up about 33% of the disease in the United States, making it the most common type of NHL in this country. Originated in the lymph nodes, this lymphoma can spread rapidly in the body. DLBCL can affect any age group but occurs mostly in older people. About 40% to 50% of DLBCL patients are cured with therapy.
We have received funding from the Small Business Innovation Research program of the National Cancer Institute to begin a Phase I/II clinical trial examining the combination of Veltuzumab with yttrium-90-labeled Epratuzumab in patients with relapsed DLBCL.
ITP is an autoimmune disease in which the immune system attacks the platelets (or thrombocytes) resulting in their accelerated destruction. It is a bleeding disorder characterized by low blood platelet counts of less than 50 x 109/L. The incidence of adult ITP is approximately 10 – 125 cases per 1,000,000 per year, and predominantly affects females with onset between 18 to 40 years of age. Treatment is usually required for platelet levels below 30 x 109/L because of high risk of bleeding. Conventional initial therapy is corticosteroids with or without intravenous immunoglobulins, but many patients relapse when steroids are tapered. Standard treatment in this situation has been splenectomy, which results in durable complete remission in 60 – 70% of cases. For patients who do not respond to corticosteroids, immunoglobulins, or splenectomy, the FDA has recently approved two new agents that mimic thrombopoietin, the major platelet growth factor that stimulates the production of platelets by the bone marrow.
For more information on ITP, please visit ncbi.nlm.nih.gov.
Veltuzumab in a subcutaneous formulation is currently being evaluated in a Phase I/II clinical trial in adult patients with chronic ITP. For more information, please go to clinicaltrials.gov.
Multiple myeloma is a cancer of the plasma cells, a type of white blood cell, with occurrence at multiple bone marrow sites. In multiple myeloma, plasma cells constitute 10-80% of the bone marrow cells compared to 1% in normal bone marrow cells. Consequently, abundance of one type of antibody is produced by the B cells, thereby severely limiting the body’s ability to fight infections, leading to localized bone fractures, weakening of muscles, and stress on kidney function.
The disease typically occurs in the older population. According to the National Cancer Institute , there will be an estimated 20,520 new cases of multiple myeloma and 10,610 deaths from this disease in the United States in 2011. As such, this indication constitutes an Orphan Disease.
The mainstay of multiple myeloma treatment has been chemotherapy consisting of alkylating agents such as cyclophosphamide, melphalan or carmustine, as well as combination chemotherapies with agents such as vincristine, doxorubicin and dexamethasone. More recently, therapies such as bortezomib and thalidomide that target cancer cellular pathways have been approved. The 5-year relative survival rate for multiple myeloma is around 40%.
The doxorubicin conjugate of Milatuzumab is in a Phase I trial for the treatment of patients with recurrent multiple myeloma. For more information on this study, please visit clinicaltrials.gov.
Pancreatic cancer is often called a silent disease because it is difficult to detect and symptoms do not usually appear until the cancer has grown and often spread beyond the pancreas for quite some time. When symptoms do appear, they can be confused with other diseases. Depending on the stage and location of the cancer, surgery, chemotherapy and/or radiation therapy are used to treat this disease, but if the cancer has spread beyond the pancreas, therapy often is palliative, or focused on comforting the patient.
According to the National Cancer Institute, an estimated 37,660 Americans will die from pancreatic cancer in 2011, making the disease the fourth leading cause of cancer death in the United States. It is also the eighth most frequently diagnosed cancer with about 44,030 new cases expected in 2011.
The cause of pancreatic cancer is not known, but a small percentage of people develop the disease as a result of a genetic predisposition, because they have a close relative, with pancreatic cancer, which gives them a higher risk of developing this disease. Smoking is also considered to be a risk factor. There is no symptom at the early stage, nor is there yet a reliable screening test for early detection. Pain is often felt in the upper abdomen and sometimes, the back, as one of the earliest symptoms and it is exacerbated after meals or when lying down. Other symptoms include loss of appetite, weight loss, nausea, and general fatigue. If the common bile duct is blocked by the tumor, jaundice appears, which in whites colors the skin and whites of the eyes yellow, and colors the urine dark in all patients with jaundice.
Treatment options depend on stage and location of the cancer, age, and general health of the patient. Potentially curative surgeries are performed when the cancer has started in the head of the pancreas (near the bile duct), which can allow earlier detection when bile duct blockage produces jaundice. Palliative surgery is a type of surgery chosen when the tumor is too widespread and is done to relieve the symptoms or complications caused by the cancer. If the cancer has not spread beyond the pancreas, therapy can be successful, but it is rare to find pancreatic cancer in the early stages. In later stages, various forms of chemotherapy or combinations of radiation and chemotherapy are given to try to control the disease, and ultimately therapy strives to comfort the patient and reduce pain. For all stages combined, the 1- and 5-year relative survival rates are 26% and 6%, respectively. For patients with advanced cancers, the median survival is 5.65 months.
Currently, the standard therapy for pancreatic cancer is gemcitabine, alone or in combination with other chemotherapeutics. Gemcitabine became the standard treatment for advanced pancreatic cancer more than 12 years ago, after it was found to be superior to fluorouracil. Numerous Phase-III trials of newer cytotoxic drugs or biological agents in combination with gemcitabine have failed to demonstrate any survival improvement compared with gemcitabine alone except for erlotinib, which has been approved in combination with gemcitabine. The combination showed a median survival of 6.24 months compared to 5.91 months for gemcitabine alone, but the objective response rates were not significantly different; median one-year survival rates were 23% vs. 17%, respectively. The overall disease control rate (partial response and stable disease rates) was 57.5% for the combination and 49.2% for the gemcitabine arm, which was not statistically different. The frequency of drug-related toxicities was higher for the combination than for gemcitabine-alone, including generally grade-1/2 skin rash, diarrhea, infection, and mouth sores, grade 3-4 neutropenia and thrombocytopenia, and grade 3 or higher liver function enzyme elevation.
Clivatuzumab is currently being investigated in a Phase Ib/II clinical trial for the therapy of patients with advanced pancreatic cancer. More information on this trial can be accessed at clinicaltrials.gov.
Rheumatoid arthritis is an autoimmune disease in which the immune system attacks the membrane that lines the joints resulting in fluid build-up, causing pain in the joints and inflammation that can occur throughout the body. It is a chronic disorder that affects approximately 1.3 million people in the United States – about 1 percent of the nation’s adult population, with nearly three times as many women as men with the disease. While the cause of rheumatoid arthritis is not known, the disease can occur at any age and is found in all ethnic groups and in every part of the world.
Current treatments for rheumatoid arthritis can be divided into two groups. Those that reduce inflammation include aspirin, corticosteroids, and nonsteroidal anti-inflammatory drugs such as ibuprofen, naprosen and celecoxib. Those that modify the disease include methotrexate and leflunomide, as well as antimalarial medications such as hydroxychloroquine and sulfasalazine.
In addition, a number of targeted therapies have been approved to treat rheumatoid arthritis. These include abatacept and rituximab that target white blood cells; adalimumab, etanercept, infliximab, golimumab, and certolizumab that inhibit the inflammatory process, as well as tocilizumab that blocks the activity of interleukin-6.
The subcutaneous formulation of Veltuzumab is in a double blind, placebo-controlled, multicenter, multinational Phase II dose-range finding trial in patients with moderate to severe rheumatoid arthritis. More information on the VELVET trial can be obtained from clinicaltrials.gov.
SLE, commonly referred to as lupus, is a chronic and potentially fatal autoimmune disease with a variable and unpredictable course. Antibodies are generated against the body’s own nuclear proteins causing the immune system to attack its own cells and tissues resulting in inflammation and tissue damage. This can occur in any part of the body, but most often targets the heart, joints, skin, lungs, blood vessels, liver, kidneys and nervous system.
Lupus is characterized by periods of flares, or exacerbations, interspersed with periods of improvement or remission. The Lupus Foundation of America estimated that between 1.5-2 million Americans have a form of lupus, 90 percent of whom are women. Symptoms and diagnosis occur most often between the ages of 15 and 45. In the U.S., lupus is more common in African Americans, Latinos, Asians, and Native Americans than in Caucasians.
Epratuzumab is currently in 2 multicenter, placebo-controlled, randomized, double-blind studies (EMBODY™ 1 and EMBODY™ 2), designed to evaluate its efficacy, safety, tolerability, and immunogenicity in patients with moderate to severe SLE. Each study will enroll 780 subjects and will last a maximum of 54 weeks.
For additional information about the EMBODY™ 1 trial, please see clinicaltrials.gov.
For additional information about the EMBODY™ 2 trial, please see clinicaltrials.gov.
