AstraZeneta immunotoxin Lumoxiti approved by FDA to treat hair cell leukemia (HCL)

British pharmaceutical giant AstraZeneca and its global biologics development arm MedImmune recently announced that the U.S. Food and Drug Administration (FDA) has approved Lumoxiti (moxetumomab pasudotox-tdfk) for adult patients with recurring or refractic hair cell leukemia (HCL) who have previously received at least two systematic therapies, including nucleoside analogues.
Lumoxiti is an anti-CD-22 recombinant immunotoxin, an innovative drug at the first-in-class level that has previously been granted priority review by the FDA. The approval marks a major milestone in the clinical treatment of HCL by making Lumoxiti the first new drug approved for treatment of HCL in more than 20 years.
Lumoxiti's approval is based on data from a Phase III clinical study (Study 1053). The study, a one-arm, multi-center study, was conducted in 80 adult patients who had previously received at least two options for relapse or resuscable HCL, evaluating the efficacy and safety of Lumoxiti monotherapy. The study was conducted in 34 treatment centers in 14 countries around the world. According to the study data, the total remission rate of Lumoxiti monotherapy was 75% (95% CI:64-84), the total remission rate was 41% (95% CI:30-53), and the lasting total remission rate was 30% (95% CI:20-41). After 16.7 months of mid-level follow-up, the duration of the mid-completely remission has not yet been reached.
HCL is a rare, incurable and slow-moving chronic lymphatic proliferating leukemia characterized by anemia, bleeding, swelling of the spleen and a large number of white blood cells with untidy edges and pseudo-foot-like or slender hair. HCL can lead to serious, life-threatening consequences, including severe infection, bleeding and anemia.
immunotoxin is a class of anti-cancer agents that use the selectivity of antibodies to target drug delivery and the ability of toxins to kill cancer cells. Lumoxiti is made up of a binding domain of anti-CD22 antibodies that fuses with toxins. CD22 is a type I transfilm protein expressed mainly in mature B lymphocytes, which plays an important role in B cell signaling. There is a higher density CD22 on HCL cells than on normal B cells, making it a very attractive therapeutic target for the treatment of HCL. When Lumoxiti binds to CD22, it internalizes, processes and releases modified protein toxins, inhibiting the translation of proteins in cells and causing apoptosis. In the United States, the FDA has granted Lumoxiti orphan drug status (ODD) and fast-track status for the treatment of HCL.
estimated that about 1,000 people in the United States are diagnosed with HCL each year. Currently, HCL does not have a mature standard care plan. Although many patients show remission in the early stages of treatment, up to 30%-40% of patients relapse within 5-10 years of first treatment. In the subsequent treatment, the mitigation time is shortened, the toxicity accumulates, and there are few treatment options. Lumoxiti represents a very promising non-chemotherapy drug that promises to address significant unsecured medical needs in the population of patients with relapsed or resuscable HCL.
drug administration, Lumoxiti has a recommended dose of 0.04 mg/kg body weight, intravenous administration time of >30 minutes, and administration on the 1st, 3rd and 5th days of a cycle at 28 days, until 6 cycles of treatment or the progression or unacceptable toxicity of the disease. It is important to note that Lumoxiti is not recommended for patients with severe renal dysfuncation (Creatinine removal rate (CrCl<29mL). (Bio Valley)