Henrique Orlandi Mourao
Hairy cell leukemia Image from Paulo
The US Food and Drug Administration (FDA) has accepted for priority review the biologics license application (BLA) for moxetumomab pasudotox, an investigational anti-CD22 recombinant immunotoxin.
With this BLA, AstraZeneca is seeking approval for moxetumomab pasudotox for the treatment of adults with hairy cell leukemia (HCL) who have received at least 2 prior lines of therapy.
The FDA expects to make a decision on the BLA in the third quarter of this year.
The FDA aims to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
The agency grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
About moxetumomab pasudotox
Moxetumomab pasudotox (formerly CAT-8015 or HA22) is composed of a binding portion of an anti-CD22 antibody fused to a toxin. After binding to CD22, the molecule is internalized, processed, and releases its modified protein toxin, which inhibits protein translation and leads to apoptosis.
In addition to priority review, moxetumomab pasudotox has received orphan drug designation from the FDA.
Moxetumomab pasudotox has been tested in a phase 1 trial. Initial results from this trial were published in the Journal of Clinical Oncology in 2012. Long-term follow-up was presented at the 2017 ASH Annual Meeting.
The ASH data included 49 patients with relapsed/refractory HCL. Their median age was 57 (range, 40-77), most (n=41) were male, and they had a median of 35 (range, 1-60,444) circulating HCL cells/mm3 at baseline (in 48 evaluable patients).
Twenty-eight patients received moxetumomab pasudotox in the dose-escalation portion of the study—at 5, 10, 20, 30, 40, or 50 µg/kg—and 21 received the drug at 50 µg/kg for the extension portion of the study.
Among the 33 patients who received moxetumomab pasudotox at 50 µg/kg, the overall response rate was 88%, and the complete response (CR) rate was 64% (n=21). The median time to CR was 3.6 months, and the median duration of CR was 70.3 months.
The median follow-up was 75 months for the entire study population. At 72 months, the progression-free survival (PFS) rate was 77%.
The researchers found that minimal residual disease (MRD) negativity (via immunohistochemistry) was associated with extended response duration and prolonged PFS.
The MRD evaluation included 19 MRD+ patients and 18 MRD- patients. Forty-seven percent of the MRD+ patients (n=9) and 94% of the MRD- patients (n=17) had a CR as their best response.
The median duration of CR was 13.1 months among the MRD+ patients and was not reached among the MRD- patients (P=0.0002). The median PFS was 82.1 months among the MRD+ patients and not reached among the MRD- patients (P=0.0031).
Moxetumomab pasudotox did not undergo phase 2 testing but proceeded to a phase 3 trial. In this single-arm study, researchers evaluated the drug in HCL patients who had received at least 2 prior therapies.
According to AstraZeneca, the study’s primary endpoint—durable CR—was met. The company said the phase 3 results will be presented at an upcoming medical meeting.