AstraZeneca Discontinues Moxetumomab Pasudotox for Hairy Cell Leukemia Due to Low Clinical Uptake
核心洞察
AstraZeneca announced the permanent discontinuation of moxetumomab pasudotox-tdfk (Lumoxiti) from the US market for relapsed/refractory hairy cell leukemia (搜索), effective July 2023.
The withdrawal is attributed to very low clinical uptake since FDA approval in 2018, despite the drug's proven efficacy with a 75% objective response rate.
The company cited availability of other treatment options and the specialized complexity of administration as factors contributing to limited adoption.
AstraZeneca has announced the permanent discontinuation of moxetumomab pasudotox-tdfk (Lumoxiti) from the United States market for the treatment of relapsed/refractory hairy cell leukemia (搜索) (HCL). The company plans to remove the CD22 (搜索)-directed cytotoxin from the market in July 2023 and will advise distributors to halt distribution in August 2023.
The decision to withdraw the agent is not related to efficacy or safety concerns, according to AstraZeneca's letter to healthcare providers. Instead, the company cited "very low clinical uptake" since FDA approval on September 23, 2018, attributing this to "the availability of other treatment options and possibly due to the specialized complexity of administration, toxicity prophylaxis, and safety monitoring needs for patients."
Current Indication and Treatment Protocol
Moxetumomab pasudotox is currently indicated for adult patients with relapsed/refractory HCL who have received at least 2 prior lines of therapy, including treatment with a purine nucleoside analog. The drug was administered at 40 μg/kg intravenously on days 1, 3, and 5 of each 28-day cycle.
AstraZeneca has advised physicians not to initiate new treatment with moxetumomab pasudotox with immediate effect. Patients who were undergoing treatment as of the November 18, 2022 letter had time to complete 6 cycles of therapy.
Clinical Trial Data Supporting Approval
The 2018 FDA approval was based on findings from a pivotal phase 3 trial (NCT01829711) that demonstrated significant efficacy in heavily pretreated patients. The CD22 (搜索)-directed recombinant immunotoxin achieved an objective response rate of 75%, with 30% of patients experiencing a complete remission (CR) lasting more than 180 days.
The trial enrolled patients with relapsed/refractory HCL who had received at least 2 prior systemic therapies, including at least 1 purine nucleoside analog. Of the enrolled patients, 50 (62.5%) completed a full 6 cycles of treatment. The most common reasons for treatment discontinuation were CR with minimal residual disease (MRD) negativity (15%) and adverse effects (15%).
Updated findings from the trial showed impressive long-term outcomes at a median follow-up of 24.6 months. The durable CR rate (CR with hematologic remission of more than 180 days) reached 36% (95% CI, 26%-48%), with a CR with hematologic remission of at least 360 days of 33%, and an overall CR of 41%. Among complete responders, 82% were MRD-negative, and 61% achieved a CR lasting at least 60 months. The median progression-free survival without the loss of hematologic remission was 71.7 months.
Safety Profile and Monitoring Requirements
The FDA approved moxetumomab pasudotox with a Boxed Warning regarding the potential for grade 3/4 capillary leak syndrome (搜索) (CLS) and hemolytic uremic syndrome (搜索) (HUS), which occurred in 2.5% and 5% of patients, respectively. Updated safety data showed that hemolytic uremic and capillary leak syndromes were each reported in no more than 10% of patients, with no more than 5% experiencing grade 3/4 adverse effects. Importantly, adverse effects were generally reversible, and no treatment-related deaths were reported.
Impact on Ongoing Research
As part of the discontinuation process, AstraZeneca will terminate the PROXY trial (NCT04125290). This study was initiated to satisfy a post-marketing requirement to characterize the safety of moxetumomab pasudotox in patients aged 65 years and older and in patients with moderate renal impairment, defined as an estimated glomerular filtration rate of 30-59 ml/min.