Janssen Seeks FDA Approval of Teclistamab for RRMM

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by Marta Figueiredo |

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Janssen is seeking the approval of its investigational therapy teclistamab in the U.S. for people with relapsed or refractory multiple myeloma (RRMM).

“Despite all the gains that have been made in treating multiple myeloma, the unmet need still remains very high,” Peter Lebowitz, MD, PhD, global therapeutic area head of oncology at Janssen research and development, said in a press release. “Our relentless pursuit of treatments for this disease continues with the same sense of urgency that we have always had. We look forward to working with the FDA in their review of our teclistamab submission.”

The company has submitted a biologics license application to the U.S. Food and Drug Administration (FDA) — “another important step in our commitment to bring to patients truly transformational medicines that profoundly impact their health,” said Mathai Mammen, MD, PhD, global head of Janssen research and development.

“The deep expertise, creativity and persistence of the entire Janssen R&D organization enabled the expeditious advancement of teclistamab for multiple myeloma,” he added.

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Teclistamab is an investigational, off-the-shelf, bispecific antibody that directs cancer-killing immune T-cells towards myeloma cells by binding to proteins on the surface of both cell types. Specifically, the antibody binds to the CD3 surface receptor on T-cells and the B-cell maturation antigen (BCMA) on myeloma cells, linking them and activating an immune response.

Considered one of the most promising targets for myeloma, BCMA is a protein found at high levels on the surface of myeloma cells, but present at minimal levels in healthy cells.

Teclistamab received orphan drug designation in both the U.S. and European Union (EU) for the treatment of multiple myeloma. It was also designated a breakthrough therapy in the U.S. and a priority medicine in the EU for treating RRMM.

The regulatory submission was supported by data from the ongoing MajesTEC-1 Phase 1/2 clinical trial, which is evaluating teclistamab’s safety and effectiveness in about 200 adults with RRMM.

The study’s Phase 1 part (NCT03145181) tested ascending doses of the therapy, delivered either directly into the bloodstream or through under-the-skin injections, to determine the best dose and regimen to be further evaluated in its Phase 2 part (NCT04557098).

Teclistamab’s recommended dose — weekly under-the-skin injections of 1.5 mg/kg — is associated with durable responses that are deepened over time, according to MajesTEC-1’s latest data, which were shared in an oral presentation at the 2021 American Society of Hematology Annual Meeting.

The clinical cut-off covered 150 patients who were treated with the recommended dose across the Phase 1 and 2 parts and had received at least three prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and a CD38 inhibitor.

At a median follow-up of nearly eight months, 62% of patients had experienced a reduction in cancer burden, regardless of genetic risk factors and failure to respond to prior therapies. The median time to first confirmed response was 1.2 months.

About 58% of patients showed a very good partial response or better, 29% achieved a complete response or better, and 21% attained a stringent complete response, or no detectable cancer.

Among patients who achieved at least a complete response, 42% showed no minimal residual disease — the small number of cancer cells that remain in circulation after treatment and can cause a relapse.

Over half (59%) of patients were alive and without signs of disease progression after nine months, and 88% of responders were continuing treatment. This meant that the median overall survival and median duration of response had not yet been reached.

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The therapy was generally well-tolerated, with no patients needing a dose reduction.

The most common blood-related adverse events included low levels of a type of white blood cell (66%), red blood cells (50%) and platelets (38%), with up to 57% of each of these events being considered severe or life-threatening.

Other common adverse events were cytokine release syndrome (72%) — a potentially life-threatening complication of immunotherapies — skin rash at the injection site (26%), and fatigue (25%). Most of these events were mild to moderate in severity and resolved without treatment discontinuation.

Five patients (3%) developed mild to moderate neurotoxicity (damage to the brain or nervous system) that was resolved without treatment discontinuation.

Teclistamab is also being evaluated in combination with other therapies, such as Janssen’s Darzalex (daratumumab) and SpringWorks Therapeutics’ nirogacestat, in several myeloma clinical trials (NCT04586426NCT04108195, NCT04722146NCT05083169).