Alemtuzumab Wins FDA Orphan Drug Designation as Part of ALL CAR T Therapy

• The FDA has granted orphan drug designation (ODD) to alemtuzumab (CLLS52) in relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).
• Alemtuzumab is used as part of the lymphodepletion regimen for UCART22, an allogeneic chimeric antigen receptor (CAR) T-cell therapy for the same indication.
• The FDA recently granted UCART22 orphan drug and rare pediatric disease designations.

Alemtuzumab, an anti-CD52 antibody in the lymphodepletion regimen for UCART22, has been granted ODD by the FDA in B-ALL.¹

ODD is granted to agents that prevent, diagnose, or treat rare diseases or conditions. Drugs that have been granted ODD can be eligible for tax credits for qualified clinical trials, exemption from user fees, and a potential 7 years of market exclusivity.²

On July 26, 2024, the FDA granted the CAR T-cell therapy UCART22 orphan drug and rare pediatric disease designations.³ Both alemtuzumab and UCART22 are being evaluated in the phase 1/2 BALLI-01 study (NCT04150497).

“We are excited that the FDA granted [alemtuzumab] ODD status. The importance of adding alemtuzumab to the lymphodepletion regimen has been demonstrated in Cellectis’ BALLI-01 study, where the addition of this lymphodepletion agent to the fludarabine and cyclophosphamide regimen was associated with sustained lymphodepletion and significantly higher UCART22 cell expansion allowing for greater clinical activity”, said Mark Frattini, MD, PhD, chief medical officer at Cellectis, in a press release.¹

About the BALLI-01 Trial

Alemtuzumab and UCART22 are being evaluated in the phase 1/2 BALLI-01 trial. Findings were presented at the 2023 American Society of Hematology (ASH) Annual Meeting in December 2023 and showed a preliminary response rate of 67% at dose level 2 of UCART22 vs 50% at dose level 3. Updated data are expected by the end of the year.³

The primary end points of the study are incidence of adverse events and occurrence of dose-limiting toxicities.⁴ Secondary end points include overall response rate, duration of response, progression-free survival, overall survival, and pharmacokinetics.

Patients in the trial are receiving the CD22-targeting UCART22 with the CD52-targeting monoclonal antibody alemtuzumab. Those aged 15 to 70 are eligible for enrollment in the study if they have B-ALL blast cells expressing CD22, have been diagnosed with relapsed or refractory B-ALL, and have received at least 1 standard chemotherapy regimen and 1 salvage regimen. Those who have received cellular or gene therapy within 60 days of enrollment are not eligible for study enrollment.

The study is enrolling across locations in California, Colorado, Illinois, Massachusetts, New York, Pennsylvania, Tennessee, Texas, and France and has an estimated completion date of January 31, 2026.

REFERENCES:

1. FDA grants orphan drug designation to Cellectis’ CLLS52 (alemtuzumab) for ALL treatment. News release. Cellectis. August 1, 2024. Accessed August 5, 2024. https://tinyurl.com/mryrcyxh

2. Designating an orphan product: drugs and biological products. News release. FDA. Updated July 8, 2022. Accessed August 5, 2024. https://tinyurl.com/24muw8am

3. FDA grants orphan drug and rare pediatric disease designation status to Cellectis’ UCART22 product candidate for acute lymphoblastic leukemia (ALL) treatment. News release. Cellectis. July 25, 2024. Accessed August 5, 2024. https://tinyurl.com/bddextw8

4. Phase 1/​2 study of UCART22 in patients with relapsed or refractory CD22+ B-cell acute lymphoblastic leukemia (BALLI-01). ClinicalTrials.gov. Updated September 25, 2023. Accessed August 5, 2024. https://clinicaltrials.gov/study/NCT04150497