On 24 March 2022, the European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a conditional marketing authorisation for the medicinal product ciltacabtagene autoleucel (Carvykti), intended for the treatment of adult patients with relapsed and refractory multiple myeloma.

As Carvykti is an advanced therapy medicinal product, the CHMP positive opinion is based on an assessment by the Committee for Advanced Therapies.

The applicant for this medicinal product is Janssen-Cilag International NV.

Carvykti will be available as 3.2 x 10⁶ to 1.0 x 10⁸ cells dispersion for infusion. The active substance of Carvykti is ciltacabtagene autoleucel, a genetically modified autologous T cell immunotherapy consisting of modified T-cells bearing a chimeric antigen receptor (CAR) targeting B-cell maturation antigen (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. Upon binding to BCMA-expressing cells, the CAR promotes T cell activation, expansion, and elimination of target cells.

The main study on which the recommendation for a conditional marketing authorisation is based, is a single arm, open-label, multicentre clinical study. The study investigated the efficacy and safety of ciltacabtagene-autoleucel in 113 adult patients with relapsed and refractory multiple myeloma who had received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and who didn’t respond to the last treatment regimen. About 84% of patients enrolled in the study responded to the treatment with a durable response. Around 69% showed a complete response.

The most common side effects are neutropenia, cytokine release syndrome (CRS), pyrexia, thrombocytopenia, anaemia, leukopenia, lymphopenia, musculoskeletal pain, hypotension, fatigue, transaminase elevation, upper respiratory tract infection, diarrhoea, hypocalcaemia, hypophosphataemia, nausea, headache, cough, tachycardia, chills, encephalopathy, decreased appetite, oedema and hypokalaemia.

The consequences of CRS can be life-threatening and, in some cases, even fatal. Furthermore, other important safety aspects are neurologic toxicity, prolonged cytopenia and serious infections. Monitoring and mitigation strategies for these side effects are described in the product information and in the risk management plan that is an integral part of the authorisation.

Additional risk minimisation measures required from the marketing authorization holder will ensure that centres that dispense the therapy are qualified to recognise and manage CRS and neurotoxicity associated with the treatment of Carvykti.

The full indication is:

Carvykti is indicated for the treatment of adult patients with relapsed and refractory multiple myeloma, who have received at least three prior therapies, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy.

Carvykti should be prescribed by physicians experienced in the treatment of haematological malignancies and trained for administration and management of patients treated with Carvykti.

Detailed recommendations for the use of this product will be described in the summary of product characteristics, which will be published in the European public assessment report and made available in all official European Union languages after the marketing authorisation has been granted by the European Commission.

Summaries of positive opinion are published without prejudice to the Commission decision, which will normally be issued 67 days from adoption of the opinion.

A conditional marketing authorisation is granted to a medicinal product that fulfils an unmet medical need when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required. The marketing authorisation holder is expected to provide comprehensive clinical data at a later stage.

Additional efficacy and safety data are being collected through the submission of follow-up data from the main clinical study and through an ongoing study that will compare the efficacy and safety of the medicine with standard triplet regimens in patients with relapsed and lenalidomide-refractory multiple myeloma.

This product was designated as an orphan medicine during its development. EMA will now review the information available to date to determine if the orphan designation can be maintained.

Carvykti had support through the PRIME scheme, EMA’s platform for early and enhanced dialogue with developers of promising new medicines that address unmet medical needs.

The opinion adopted by the CHMP is an intermediary step on Carvykti’s path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each EU Member State, taking into account the potential role or use of this medicine in the context of the national health system of that country.