FDA Roundup: Biosimilars, Boxed Warning Added for CAR T-Cell Therapies

FDA Approves Stelara Biosimilar Ustekinumab-aekn

Ustekinumab (Stelara) biosimilar ustekinumab-aekn (Selarsdi) has been approved by the FDA to treat moderate to severe plaque psoriasis and active psoriatic arthritis in adults and children aged 6 years and older, Alvotech and Teva Pharmaceuticals announced in a release.¹ The companies said the availability of the biosimilar will saves costs for health care systems and provide more treatment options for patients.

The FDA approval was based on data from a clinical development program that included 2 trials: the randomized, double-blind, multicenter, 52-week AVT04-GL-301 study (NCT04930042) and the phase 1, randomized, double-blind, single-dose, parallel-group, 3-arm study ATV04-GL-101 (NCT04744363). The studies compared the pharmacokinetic, safety, tolerability, and immunogenicity profiles of the biosimilar vs the reference product.

Ustekinumab is a human monoclonal antibody that selectively targets the p40 protein, a common component of interleukin-12 (IL-12) and IL-23—both of which play crucial rules in the treatment of immune mediated diseases.

READ MORE: GAO Releases Report on States’ Regulation of PBMs

FDA Moves to Require Boxed Warning for CAR T-Cell Immunotherapies

The FDA has announced that it is now requiring boxed warnings on all approved BCMA-directed and CD19-directed genetically modified autologous CAR T-cell therapies due to a serious risk of T cell malignancies, the agency announced in a release.² Additionally, the FDA is also requiring related updates to other sections of CAR T-cell therapy labels, including warnings and precautions, and postmarketing experience.

The decision comes after an FDA investigation that began in November 2023. The agency had received reports of T cell malignancies—including chimeric antigen receptor CAR-positive lymphoma—in patients treated with the therapies. Then, in January 2024, the FDA initiated class safety labeling changes and subsequently concluded that the warnings are warranted.

The included approved therapies are: idecabtagene vicleucel (ide-cel; Abecma), lisocabtagene maraleucel (liso-cel; Breyanzi), ciltacabtagene autoleucel (cilta-cel; Carvykti), tisagenlecleucel (tisa-cel; Kymriah), brexucabtagene autoleucel (brexu-cel; Tecartus), and axicabtagene ciloleucel (axi-cel; Yescarta).

First ALK Inhibitor for Adjuvant Therapy in Early-Stage NSCLC Approved by FDA

The FDA has approved alectinib (Alecensa) as an adjuvant therapy after tumor resection for patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC), Genentech announced in a release.³ The decision makes alectinib the first and only ALK inhibitor approved for patients with ALK-positive early-stage NSCLC who underwent surgery to remove their tumor.

The FDA approval was based on data from the ALINA (NCT03456076) study, a randomized, active-controlled, multicenter, open-label, phase 3 trial investigating the efficacy and safety of alectinib compared with platinum-based in the adjuvant setting. The study demonstrated that alectinib reduced the risk of disease recurrence or death by 76% in patients with completely resected IB to IIIA ALK-positive NSCLC. The safety and tolerability of alectinib were consistent with previous trials in the metastatic setting.

Alectinib is a kinase inhibitor that’s currently approved as a first- and second-line treatment for ALK-positive metastatic NSCLC. A 600-mg dose of alectinib is recommended to be given orally twice a day with food for 2 years or until unacceptable toxicity or disease recurrence.

READ MORE: FDA Update Resource Center

References

1. Alvotech and Teva announce US FDA approval of Selarsdi (ustekinumab-aekn), biosimilar to Stelara (ustekinumab). News release. Teva. April 16, 2024. Accessed April 19, 2024. https://www.tevapharm.com/news-and-media/latest-news/alvotech-and-teva-announce-u.s.-fda-approval-of-selarsdi-ustekinumab-aekn-biosimilar-to-stelara-ust

2. FDA requires boxed warning for T cell malignancies following treatment with BCMA-directed or CD19-directed autologous chimeric antigen receptor (CAR) T cell immunotherapies. News release. FDA. April 18, 2024. Accessed April 19, 2024. https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/fda-requires-boxed-warning-t-cell-malignancies-following-treatment-bcma-directed-or-cd19-directed

3. FDA Approves Genentech's Alecensa as First Adjuvant Treatment for People With ALK-Positive Early-Stage Lung Cancer. News release. Genentech. April 18, 2024. Accessed April 18, 2024. https://www.gene.com/media/press-releases/15023/2024-04-18/fda-approves-genentechs-alecensa-as-firs