Tecvayli Approved in US for Heavily Pre-treated RRMM, With Conditions

Patients must have received 4 lines of therapy and be monitored under REMS

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by Patricia Inácio, PhD |

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Janssen’s Tecvayli (teclistamab) has been approved for certain adults with relapsed or refractory multiple myeloma in the U.S., but access is limited due to potential side effects.

In particular, the approval by the U.S. Food and Drug Administration (FDA) is for patients who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and a CD38 inhibitor.

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Tecvayli designed to direct immune system against myeloma cells

Tecvayli is an off-the-shelf, bispecific antibody designed to direct the immune system’s killing response against myeloma cells. It works by simultaneously binding to BCMA, a marker mainly found on myeloma cells, and to CD3, a protein expressed by cancer-killing immune cells called T-cells. The therapy is administered as an under-the-skin injection.

“As a clinician and researcher, I see first-hand the human toll of this incurable disease,” Ajai Chari, MD, professor at the Icahn School of Medicine at Mount Sinai, one of the trial’s researchers, said in a press release. “The approval of teclistamab, as the first bispecific antibody in relapsed or refractory multiple myeloma, is a meaningful step in helping many of these hard-to-treat patients.”

However, the FDA placed limitations to its access, as healthcare providers and pharmacies need to be registered in the Tecvayli Risk Evaluation and Mitigation Strategy (REMS) program, which will focus on monitoring and counseling patients due to a high rate of serious side effects linked to the medication. This includes cytokine release syndrome — a potentially life-threatening complication of immunotherapies — and neurological side effects.

[Tecvayli] is an important new treatment option for patients who have faced multiple relapses

“We are greatly encouraged by the FDA’s approval of teclistamab and Janssen’s commitment to the multiple myeloma community,” said Michael Andreini, president and CEO of the Multiple Myeloma Research Foundation. “Multiple myeloma is a life-threatening disease with considerable unmet need, and teclistamab is an important new treatment option for patients who have faced multiple relapses.”

The approval was supported by early positive findings from the ongoing MajesTEC-1 Phase 1/2 study, which is evaluating Tecvayli’s safety and effectiveness in about 200 adults with RRMM.

Given under the FDA’s accelerated approval program and about 10 months after the company’s application, continued approval of Tecvayli may be contingent on the final results from the MajesTEC-1 trial, according to the press release.

Tecvayli under review in Europe

A similar application is under review in Europe. Tecvayli has received a positive recommendation for approval by a branch of the European Medicines Agency. The recommendation will be reviewed by the European Commission, which will issue a final decision on its approval.

MajesTEC-1 comprises an open-label Phase 1 clinical trial (NCT03145181) and a Phase 2 clinical trial (NCT04557098), with recruitment ongoing for both phases.

Phase 1 tested ascending doses of the therapy and two administration routes, directly into the bloodstream or as under-the-skin injections to determine the best dose and regimen for Phase 2 testing.

Tecvayli’s recommended dose — weekly under-the-skin injections of 1.5 mg/kg — was linked to durable responses in Phase 2.

Specifically, data from the 110 patients, all of whom had received a median of five prior lines of therapy, showed that 61.8% had a reduction in tumor size, with 28.2% of patients achieving a complete response or stringent complete responses, meaning no detectable cancer. The median time to first confirmed response was 1.2 months, and patients were followed for a median of 7.4 months.

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“The approval of Tecvayli, which demonstrated an overall response rate of more than 60 percent in heavily pretreated patients, underscores our commitment to translate science into medicines as we strive toward our goal of one day eliminating this disease,” said Peter Lebowitz, MD, PhD, global oncology therapeutic area head at Janssen Research & Development.

The estimated duration of response — the time patients continue to respond to treatment without the cancer growing or spreading — was 90.6% after a median of six months and 66.5% after nine months.

“In the pivotal teclistamab study, we have continued to observe positive results in heavily pretreated patients with relapsed or refractory multiple myeloma,” said Chari, who is also a consultant for Janssen.

Safety data from 165 patients showed that among the most common side effects were cytokine release syndrome, which was experienced by 72% of patients. Neurotoxic events were reported in 14.5%, and 3% experienced immune effector cell-associated neurotoxicity syndrome (a condition where neurotoxicity is driven by an inflammatory immune response). A total of five reported deaths were considered related to treatment.