Janssen's BCMA CAR-T Therapy Cilta-cel Granted Accelerated Assessment by EMA for Relapsed/Refractory Multiple Myeloma
Janssen Pharmaceuticals
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Committee for Medicinal Products for Human Use
Committee for Medicinal Products for Human Use (CHMP)The Committee for Medicinal Products for Human Use (CHMP) is the committee within the European Medicines Agency (EMA) responsible for human medicines. The CHMP replaced the former Committee for Proprietary Medicinal Products (CPMP) in May 2004.The CHMP plays a vital role in the authorization of medicines in the European Union (EU). In the centralized procedure, the CHMP is responsible for: 1) conducting initial assessments of marketing authorization applications across the EU; assessing modifications or extensions to existing marketing authorizations (“variations”); considering recommendations from the Agency’s Pharmacovigilance Risk Assessment Committee regarding the safety of medicines on the market, and, where necessary, advising the European Commission to amend the marketing authorization of a medicinal product, or to suspend or withdraw it from the market.The CHMP also evaluates medicines authorized at the national level that are referred to the EMA, with the aim of maintaining a harmonized position throughout the EU.Furthermore, the CHMP and its working groups promote the development of medicines and pharmaceutical regulation by: providing scientific advice to companies researching and developing new medicines; developing scientific and regulatory guidelines to assist pharmaceutical companies in preparing marketing authorization applications for human medicines; and collaborating with international partners to harmonize regulatory requirements.
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On February 1, Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson, announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency would conduct an accelerated assessment of the Marketing Authorization Application (MAA) for ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T-cell (CAR-T) therapy. The CHMP typically grants accelerated assessment to medicines expected to offer significant public health benefits and therapeutic innovation, which will significantly shorten the review timeline for the MAA.
Cilta-cel is an investigational BCMA-directed CAR-T cell therapy currently being developed for the treatment of relapsed and/or refractory multiple myeloma (MM). Its design incorporates a structurally differentiated CAR-T construct containing two BCMA-targeting single-domain antibodies. CAR-T cell therapy is an innovative approach that harnesses the patient’s own immune system to eliminate cancer cells. BCMA is a protein highly expressed on myeloma cells.
Johnson & Johnson aims to submit the Marketing Authorization Application (MAA) for cilta-cel in the first half of 2021. This accelerated assessment by the European Union represents another regulatory milestone for cilta-cel. Last December, the company initiated a rolling submission of the Biologics License Application (BLA) for cilta-cel to the U.S. Food and Drug Administration (FDA). Previously, the FDA had granted Breakthrough Therapy Designation (BTD) to cilta-cel and agreed to a rolling review of the BLA; the European Medicines Agency (EMA) had granted cilta-cel Priority Medicines (PRIME) designation and Orphan Drug designation. In August 2020, China’s National Medical Products Administration (NMPA) also included cilta-cel in its Breakthrough Therapy Drug Program.
In December 2017, Janssen Biotech, a subsidiary of Johnson & Johnson, entered into an exclusive global license and collaboration agreement with Nanjing Legend Biotech to develop and commercialize cilta-cel. Based on the analysis of the LEGEND-2 study results, Janssen initiated the Phase Ib/II CARTITUDE-1 clinical trial (NCT03548207) in May 2018 to evaluate the efficacy and safety of cilta-cel in adult patients with relapsed and/or refractory multiple myeloma (MM).
Positive results from the CARTITUDE-1 study supported the regulatory application for cilta-cel. In this study, 99% of patients were refractory to their last line of therapy, and 88% had triple-class refractory disease, meaning their cancer did not respond or had lost response to immunomodulatory agents, proteasome inhibitors, and anti-CD38 antibodies.
The latest results from this study were presented at the 2020 American Society of Hematology (ASH) Annual Meeting. The data demonstrated that cilta-cel treatment achieved a very high overall response rate (ORR), with responses deepening over time. Specifically, based on assessments by an independent review committee, after a median follow-up of 12.4 months, up to 97% of patients achieved a response, and 67% of patients attained a stringent complete response. The median time from treatment initiation to first response was 1 month; the median progression-free survival (PFS) had not been reached, with a 12-month PFS rate of 77% and a 12-month overall survival rate of 89%.
BCMA-Targeted Therapy (Image from Reference Source 2)
BCMA is a hot target in the development of new drugs for multiple myeloma. Therapies targeting this antigen are mainly divided into three categories: CAR-T, bispecific antibodies (BsAb), and antibody-drug conjugates (ADC). Among them, Blenrep, a BCMA-targeting ADC therapy from GlaxoSmithKline, was approved in the US and Europe in August 2020, becoming the first approved BCMA-targeted therapy globally.
In the field of CAR-T therapy, Bristol Myers Squibb/Bluebird Bio’s idecabtagene vicleucel (ide-cel) is undergoing priority review by the U.S. FDA and accelerated assessment by the European EMA. In the United States, the FDA’s target action date is March 27, 2021. Clinical data show that the overall response rate for ide-cel treatment is 73%, with a complete response rate of 33%.
In the field of bispecific antibodies (BsAbs), subcutaneous BCMAxCD3 therapies from Johnson & Johnson and Pfizer have both demonstrated impressive performance. Data presented at the 2020 ASH Annual Meeting showed that Janssen’s teclistamab achieved an overall response rate (ORR) of 73% at the recommended Phase 2 dose, while Pfizer’s PF-06863135 reached an ORR of 83% at the highest dose.
References:
1.Janssen Announces CAR-T Therapy Ciltacabtagene Autoleucel (Cilta-cel) Accepted for Accelerated Assessment in Europe for the Treatment of Patients with Heavily Pretreated Multiple Myeloma
2.Targeting B Cell Maturation Antigen (BCMA) in Multiple Myeloma: Potential Uses of BCMA-Based Immunotherapy
*Disclaimer: This article was written by an author contributing to Sina Medical News. The views expressed are solely those of the author and do not represent the position of Sina Medical News.