First-in-Class Immunotoxin Lumoxiti Receives EU Approval for Hairy Cell Leukemia After Two Decades

February 13, 2021 /BioValleyBIOON/ -- According to the latest data from the European Union's New Drug Approval Database,AstraZeneca(AstraZeneca) The anticancer drug Lumoxiti (moxetumomab pasudotox) has recently been approved by the European Commission (EC). This drug is an anti-CD22 recombinant immunotoxin used to treat relapsed or refractory hairy cell leukemia in patients who have failed at least two prior systemic therapies, including purine nucleoside analogs (PNAs).Leukemia(HCL) adult patients. In the United States, Lumoxiti was approved for the above indications in September 2018, becomingThe first drug approved for the treatment of HCL in over 20 years marks a significant milestone in the clinical management of HCL.

Lumoxiti is an anti-CD22 recombinant immunotoxin and a first-in-class innovative drug for the treatment of HCL. In October 2018, French pharmaceutical company Innate Pharma SA entered into an expanded collaboration agreement with AstraZeneca to mutually promoteTumordevelopment of new drugs in the pipeline. Under the terms of the collaboration agreement, Innate Pharma was to handle the sales of Lumoxiti in the US and EU markets. However, on December 11, 2020, Innate Pharma SA announced that it would return the commercialization rights for Lumoxiti in the US and EU to AstraZeneca. The two companies will develop a transition plan with the goal of transferring all commercialization responsibilities back to AstraZeneca in 2021, ensuring patient access to Lumoxiti during the transition period. AstraZeneca will remain the marketing authorization applicant for Lumoxiti in the EU.

The approvals of Lumoxiti in the United States and the European Union were both based on data from the pivotal Phase III clinical study (Study 1053). This was a single-arm, multicenter study conducted in 80 adult patients with relapsed or refractory hairy cell leukemia (HCL) who had previously received at least two prior therapies, to evaluate the efficacy and safety of Lumoxiti monotherapy. The study was conducted across 34 treatment centers in 14 countries worldwide.

These study results were presented at the 2019 American Society of Hematology (ASH) Annual Meeting. The data showed that the overall response rate (ORR) for Lumoxiti monotherapy was 75%, and the durable complete response (CR) rate was 36% (29/80), with durable CR defined as a complete response maintained for at least 180 days. Among patients who achieved CR, 81% experienced eradication of minimal residual disease (MRD), i.e., attained an MRD-negative status. Furthermore, the probability of maintaining CR five years after achieving it was 61%.

HCL is a rare, incurable, slowly progressive chronic lymphoproliferative leukemia, characterized byAnemia, hemorrhage, splenomegaly, and the presence of abundant leukocytes with irregular margins exhibiting pseudopod-like or hairy projections in peripheral blood and bone marrow as characteristic features. HCL can lead to severe, life-threatening complications, including serious infections, hemorrhage, and anemia.

Immunotoxins are a class of anticancer agents that leverage the selectivity of antibodies for targeted drug delivery and the potent ability of toxins to kill cancer cells. Lumoxiti is composed of the binding domain of an anti-CD22 antibody fused to a toxin. CD22 is a type I transmembrane protein primarily expressed on mature B lymphocytes and plays a crucial role in B-cell signaling. Compared with normal B cells, HCL cells exhibit a higher density of CD22, making it a highly attractive therapeutic target for the treatment of HCL. Upon binding to CD22, Lumoxiti is internalized, processed, and releases the modified protein toxin, which inhibits protein translation in the cell, leading toApoptosisIn the United States and the European Union, Lumoxiti has been granted orphan drug designation (ODD) for the treatment of HCL; in the United States, it has also been granted Fast Track designation.

Currently, there is no established standard of care for hairy cell leukemia (HCL). Although many patients achieve remission during initial treatment, up to 30%–40% experience disease relapse within 5–10 years after first-line therapy. In subsequent lines of treatment, duration of remission shortens, toxicity accumulates, and therapeutic options are limited. Lumoxiti represents a highly promising non-chemotherapeutic agent that has the potential to address the significant unmet medical needs in patients with relapsed or refractory HCL.

Regarding dosing, the recommended dose of Lumoxiti is 0.04 mg/kg body weight, administered via intravenous infusion over >30 minutes on Days 1, 3, and 5 of each 28-day cycle, until completion of 6 cycles, disease progression, or unacceptable toxicity. It should be noted that Lumoxiti is not recommended for patients with severe renal impairment (creatinine clearance [CrCl] <29 mL/min). (Bioon.com)

Original Source: EU New Drug Approval Database