Moxetumomab Pasudotox Will Be Removed From US Market for Hairy Cell Leukemia

AstraZeneca has announced that they will be permanently discontinuing Moxetumomab pasudotox-tdfk (Lumoxiti) for the treatment of relapsed/refractory hairy cell leukemia (HCL) in the United States.¹

The CD22-directed cytotoxin is currently indicated for the treatment of adult patients with relapsed/refractory HCL who have received at least 2 prior lines of therapy, including treatment with a purine nucleoside analog.²

The company plans to remove moxetumomab pasudotox from the market in July 2023 and has informed the FDA of its decision. In August 2023, AstraZeneca will advise distributors to halt distribution of the agent and request the return of moxetumomab pasudotox packs.

The company wrote that the decision to withdraw the agent is not related to efficacy or safety.

“There has been very low clinical uptake of [moxetumomab pasudotox] since FDA approval on September 23, 2018, due to the availability of other treatment options and possibly due to the specialized complexity of administration, toxicity prophylaxis, and safety monitoring needs for patients,” the company wrote in the letter.

AstraZeneca advised that physicians should not initiate treatment with moxetumomab pasudotox with immediate effect. Patients currently undergoing treatment with moxetumomab pasudotox had time to complete 6 cycles of therapy as of the November 18, 2022, letter.

Additionally, the company will terminate the PROXY trial (NCT04125290). Investigators initiated the study to satisfy a post-marketing requirement to provide evidence characterizing the safety of moxetumomab pasudotox in patients aged 65 years and older and/or the safety of moxetumomab pasudotox in patients who have moderate renal impairment defined as an estimated glomerular filtration rate of 30-59 ml/min.³

The 2018 FDA approval of moxetumomab pasudotox was based on findings from a pivotal phase 3 trial (NCT01829711) that showed the CD22-directed recombinant immunotoxin elicited an objective response rate of 75%. Additionally, 30% of patients experienced a complete remission (CR) lasting more than 180 days.⁴

The trial enrolled patients with relapsed/refractory HCL who received at least 2 prior systemic therapies, including at least 1 purine nucleoside analog. Moxetumomab pasudotox was administered at 40 µg/kg intravenously on days 1, 3, and 5 of each 28-day cycle.

Fifty patients (62.5%) completed a full 6 cycles of treatment. Patients most commonly discontinued treatment due to CR with minimal residual disease (MRD) negativity (15%) and adverse effects (AEs; 15%).

Updated findings from the trial showed that at a median follow-up of 24.6 months, moxetumomab pasudotox the durable CR rate (CR with hematologic remission [HR] of more than 180 days) of 36% (95% CI, 26%-48%), a CR with HR of at least 360 days of 33%, and an overall CR of 41%.⁵ Twenty-seven complete responders (82%) were MRD-negative, and 61% of complete responder achieved a CR lasting at least 60 months. The median progression-free survival without the loss of HR was 71.7 months.

The FDA approved the agent with a Boxed Warning regarding the potential for grade 3/4 capillary leak syndrome (CLS) and hemolytic uremic syndrome (HUS), which occurred in 2.5% and 5% of patients, respectively. Updated data also showed that hemolytic uremic and capillary leak syndromes were each reported in no more than 10% of patients, and no more than 5% of patients experienced grade 3 or 4 adverse effects [AEs], and AEs were generally reversible. No treatment-related deaths were reported.

References

1. Important information for LumoxitiI® (moxetumomab pasudotox-tdfk) for injection, for intravenous Use – permanent withdrawal of LumoxitiI from the US market. Astrazeneca. November 18, 2022. Accessed January 13, 2023. https://bit.ly/3GFAL09
2. FDA approves moxetumomab pasudotox-tdfk for hairy cell leukemia. News release. FDA. September 13, 2018. Accessed January 13, 2023. http://bit.ly/3XnS4cW
3. US post-marketing safety study of moxetumomab pasudotox-tdfk (Lumoxiti) (PROXY). ClinicalTrials.gov. Updated December 9, 2022. Accessed January 13, 2023. https://clinicaltrials.gov/ct2/show/NCT04125290
4. Kreitman RJ, Dearden C, Zinzani PL, et al. Moxetumomab pasudotox in heavily pretreated patients with relapsed/refractory hairy cell leukemia: Results of a pivotal international study. Leukemia. 2018;32(8):1768-1777. doi:10.1038/s41375-018-0210-1
5. Kreitman RJ, Dearden C, Zinzani PL, et al. Moxetumomab pasudotox in heavily pre-treated patients with relapsed/refractory hairy cell leukemia (HCL): long-term follow-up from the pivotal trial. J Hematol Oncol. 2021;14(1):35. doi:10.1186/s13045-020-01004-y