Therapy Areas: Devices
Carvykti Granted Conditional Approval by the European Commission for the Treatment of Patients with Relapsed and Refractory Multiple Myeloma
27 May 2022 - - The European Commission has granted conditional marketing authorization of Carvykti (ciltacabtagene autoleucel; cilta-cel) for the treatment of adults with relapsed and refractory multiple myeloma who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy, US-based biotechnology company Legend Biotech Corp. (NASDAQ: LEGN) said.

Legend Biotech entered into an exclusive worldwide license and collaboration agreement with Johnson and Johnson's (NYSE: JNJ) Janssen Biotech, Inc. business to develop and commercialize cilta-cel in December 2017.

Carvykti is a chimeric antigen receptor T-cell (CAR-T) therapy featuring two B-cell maturation antigen -targeting single domain antibodies.

CAR-T therapy is specifically developed for each individual patient, and it is administered as a single infusion.

This approval was supported by the pivotal CARTITUDE-1 study, including patients who had received a median of six prior treatment regimens (range, 3-18), and had previously received an IMiD, PI and anti-CD38 monoclonal antibody.

Findings showed that at a median duration of 18 months follow-up (range, 1.5-30.5), a one-time treatment with cilta-cel resulted in deep and durable responses, with 98% (95% confidence interval [CI], 92.7-99.7) of patients with RRMM responding to therapy (98% overall response rate [ORR]).

Notably, 80% of the patients achieved stringent complete response, a measure in which a physician is unable to observe any signs or symptoms of disease via imaging or other tests after treatment.

The safety of cilta-cel was evaluated in 179 adult patients across two open-label clinical trials (MMY2001 and MMY2003).

As a highly personalized medicine, where a patient's own T-cells are reprogrammed to target and kill cancer cells, administration of CAR-T therapy requires extensive training, preparation, and certification to ensure the highest quality product and experience for patients.

Through a phased approach, Legend Biotech's strategic partner, Janssen, will work diligently to activate a limited network of certified treatment centers and will aim to increase availability of cilta-cel across Europe, in an effort to provide oncologists and patients with treatment in a reliable manner.

This EC Marketing Authorization follows the approval of Carvykti by the US Food and Drug Administration on February 28, 2022.

Carvykti is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient's own T-cells with a transgene encoding a chimeric antigen receptor that identifies and eliminates cells that express BCMA.

BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B-cells and plasma cells.

The Carvykti CAR protein features two BCMA-targeting single domain antibodies designed to confer high avidity against human BCMA.

Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.

In December 2017, Legend Biotech Corp. entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. (Janssen) to develop and commercialize cilta-cel.

In April 2021, Legend announced the submission of a Marketing Authorisation Application to the European Medicines Agency seeking approval of cilta-cel for the treatment of patients with relapsed or refractory multiple myeloma.

In addition to US Breakthrough Therapy Designation granted in December 2019, cilta-cel also received Breakthrough Therapy Designation in China in August 2020.

In February 2019, cilta-cel received Orphan Drug Designation from the US FDA from the European Commission in February 2020, and from the Pharmaceuticals and Medicinal Devices Agency in Japan in June 2020.

In May 2022, the Committee for Orphan Medicinal Products recommended by consensus that the orphan designation for cilta-cel be maintained, on the basis of clinical data demonstrating improved and sustained complete response rates following treatment.

Cilta-cel was approved the US Food and Drug Administration in February 2022.

CARTITUDE-1 (NCT03548207)7 is an ongoing Phase 1b/2, open-label, single arm, multi-center trial evaluating cilta-cel for the treatment of adult patients with relapsed or refractory multiple myeloma, who previously received at least three prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.

Of the 97 patients enrolled in the trial, 99% were refractory to the last line of treatment and 88 % were triple-class refractory, meaning their cancer did not respond, or no longer responds, to an IMiD, a PI and an anti-CD38 monoclonal antibody.

Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells.8 In Europe, it is estimated that more than 50,900 people were diagnosed with multiple myeloma in 2020, and approximately 32,500 patients died.

While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.

Although treatment may result in remission, unfortunately, patients will most likely relapse.

Patients who relapse after treatment with standard therapies, including protease inhibitors, immunomodulatory agents, and an anti-CD38 monoclonal antibody, have poor prognoses and few treatment options available.