Bristol Myers Squibb announced that the European Commission (EC) has granted conditional marketing authorization for idecabtagene vicleucel; ide-cel, a first-in-class B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy, 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.

Idecabtagene vicleucel; ide-cel is the first and only CAR T cell therapy approved that is directed to recognise and bind to BCMA, a protein that is nearly universally expressed on cancer cells in multiple myeloma, leading to the death of BCMA-expressing cells.

Idecabtagene vicleucel; ide-cel is delivered via a single infusion with a target dose of 420 x 106 CAR-positive viable T cells within a range of 260 to 500 x 106 CAR-positive viable T cells.

Idecabtagene vicleucel; ide-cel is approved for use in all European Union (EU) member states.

“The EC approval of idecabtagene vicleucel; ide-cel is an important milestone for the treatment of multiple myeloma, and moves us closer to offering a first-in-class, personaliSed therapy to patients in Europe battling this incurable disease after exhausting prior treatment options with the three standards of care,” said Samit Hirawat, M.D., chief medical officer, Bristol Myers Squibb.

“With this third regulatory approval for idecabtagene vicleucel; ide-cel worldwide, we are proud to be advancing the science of cell therapy and continuing to bring this first anti-BCMA CAR T cell therapy to patients in need.”

In Europe, nearly 50,000 people are diagnosed with multiple myeloma each year.

Despite advances in treatment, multiple myeloma remains an incurable disease, and many patients suffer through periods of remission and relapse.

Patients with relapsed and refractory multiple myeloma who have been exposed to all three major drug classes often have poor clinical outcomes and few remaining treatment options.

“In multiple myeloma, when a patient’s cancer is no longer responding to their current treatment regimen or the patient relapses, the disease becomes increasingly difficult to treat,” said Jesus San Miguel, M.D., Ph.D., Medical Director of the Clinica Universidad de Navarra, Navarra, Spain and KarMMa clinical trial investigator.

“In the KarMMa trial, treatment with ide-cel proved to elicit deep and durable responses in a significant proportion of patients with triple-class exposed multiple myeloma, including many who were heavily pretreated and had high-risk disease.

The approval is important for patients in Europe, as it represents another potential therapeutic option for clinically meaningful outcomes and long-term disease control.”

Bristol Myers Squibb is committed to making idecabtagene vicleucel; ide-cel commercially available to patients in the EU.

The company is currently focused on several required factors, including treatment center qualification and onboarding, completion of reimbursement procedures and scaling up its manufacturing capacity to meet increasing global demand.

The company is also actively pursuing options to expand its manufacturing global supply network to make idecabtagene vicleucel; ide-cel available to more patients around the world, including the addition of a European-based manufacturing facility in Leiden, Netherlands.

Meanwhile, Bristol Myers Squibb will continue to manufacture idecabtagene vicleucel; ide-cel for EU and U.S. patientsat the company’s state-of-the-art cellular immunotherapy manufacturing facility in Summit, New Jersey.

“Multiple myeloma patients who have tried and exhausted multiple rounds of treatment options have been hoping for new and transformative options,” said Brian G.M. Durie, Chairman, International Myeloma Foundation.

“The approval of idecabtagene vicleucel; ide-cel, an innovative anti-BCMA CAR T cell therapy, is an exciting milestone for patients in the European Union.”

Idecabtagene vicleucel; ide-cel was granted conditional marketing authorisation under the European Medicines Agency PRIME (Priority Medicines) scheme.

Conditional marketing authorisation is granted in the interest of public health where the benefit of immediate availability fulfills a critical unmet need.

Conditional marketing authorisation in the EU is initially valid for one year but can be extended or converted into a full marketing authorisation after the submission and assessment of additional confirmatory data.

For full details on the Special Warnings and Precautions for Use and Adverse Reactions (including appropriate management), please refer to the EU Summary of Product Characteristics (SmPC).

Bristol Myers Squibb offers various programs and resources to address the needs of patients and caregivers and help support access to therapies, including idecabtagene vicleucel; ide-cel.

Centralised marketing authorisation does not include approval in Great Britain (England, Scotland and Wales).

Idecabtagene vicleucel; ide-cel Clinical Trial Results

The efficacy of idecabtagene vicleucel; ide-cel is based on results from the pivotal KarMMa study in which 128 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 were refractory to the last treatment regimen were treated with idecabtagene vicleucel; ide-cel.

In the study, the overall response rate (ORR) was 73% (95% CI: 66-81), and 33% of patients achieved a complete response (CR; 95% CI: 25-41).

Onset of response was rapid with a median time to response of one month. In addition, responses were durable, with a median duration of response of 10.6 months (95% CI: 8.0 – 11.4), and 23 months (95% CI: 11.4 – 23.3) for those who achieved a CR.

In a pooled safety analysis of 184 patients treated with idecabtagene vicleucel; ide-cel in the KarMMa and CRB-401 studies, cytokine release syndrome (CRS) occurred in 81% of patients, with Grade >3 CRS, using the Lee grading system, occurring in 5.4% of patients.

There was one case of fatal (Grade 5) CRS reported. The median time to onset of CRS was one day (range: 1-17 days) and the median duration of CRS was five days (range: 1-63 days).

Any grade neurotoxicity (NT) of the 128 patients receiving idecabtagene vicleucel; ide-cel in the KarMMa study occurred in 18% of patients, including Grade 3 events in 3.1% of patients, with no Grade 4 or 5 events occurring.

The median time to onset of NT was two days (range: 1-10 days) and the median duration was three days (range: 1-26 days).

The most common (>20%) adverse reactions in the pooled safety analysis included neutropenia, CRS, anaemia, thrombocytopenia, infections - pathogen unspecified, leucopenia, fatigue, diarrhoea, hypokalaemia, hypophosphataemia, nausea, lymphopenia, pyrexia, cough, hypocalcaemia, infections - viral, headache, hypomagnesaemia, upper respiratory tract infection, arthralgia, and oedema peripheral.

The most common Grade 3 or 4 adverse reactions were neutropenia (88.6%), anaemia (58.2%), thrombocytopenia (53.5%), leucopenia (45.1%), lymphopenia (30.4%), infections - pathogen unspecified (17.9%), hypophosphataemia (17.4%), febrile neutropenia (14.7%), hypocalcaemia (7.1%), infections - viral (7.1%), pneumonia (6.0%), CRS (5.4%), hypertension (5.4%) and hyponatraemia (5.4%).

Source: Bristol Myers Squibb