U.S. FDA Approves TECVAYLI™ (teclistamab-cqyv), the First Bispecific T-cell Engager Antibody for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma

TECVAYLI™, an off-the-shelf, subcutaneous therapy, is an important new medicine for patients with incurable blood cancer who face limited treatment options

HORSHAM, Pa., Oct. 25, 2022 /PRNewswire/ -- The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) approved TECVAYLI™ (teclistamab-cqyv) for the treatment of adult patients with relapsed or refractory multiple myeloma, who previously received four or more prior lines of therapy, including a proteasome inhibitor, immunomodulatory drug and anti-CD38 monoclonal antibody.1 TECVAYLI™ is a first-in-class, bispecific T-cell engager antibody that is administered as a subcutaneous treatment.1 This off-the-shelf (or ready to use) therapy uses innovative science to activate the immune system by binding to the CD3 receptor expressed on the surface of T-cells and to the B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells.

This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s).

TECVAYLI™ is Janssen's fourth approved treatment for multiple myeloma, further diversifying the company's industry-leading oncology portfolio and deepening its commitment to discovering and developing therapies for this rare blood cancer.

"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 pivotal Phase 2 MajesTEC-1 clinical trial included patients who had received a median of five prior lines of therapy (n=110). An overall response rate (ORR) of 61.8 percent (95 percent Confidence Interval [CI]: 52.1 percent, 70.9 percent) was achieved, notably with 28.2 percent of patients achieving a complete response (CR) or better (CR or stringent complete response [sCR]).1 The median time to first response was 1.2 months (range 0.2 to 5.5 months). With a median follow-up of 7.4 months, the estimated duration of response (DOR) rate was 90.6 percent (95 percent CI: 80.3 percent, 95.7 percent) at six months and 66.5 percent (95 percent CI: 38.8 percent, 83.9 percent) at nine months.1 The study included heavily pretreated patients, and 78 percent of patients received four or more prior lines of therapy.1 All patients were triple-class exposed (to a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody), and 76 percent were triple-class refractory (to a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody).

"Today's achievement, which marks an important addition to our diverse and growing oncology portfolio, strengthens our resolve to discover and develop much-needed cancer treatments for patients and physicians," said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. "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."

The Safety Information for TECVAYLI™ includes a boxed warning for Cytokine Release Syndrome (CRS) and Neurologic Toxicity including immune effector cell-associated neurotoxicity syndrome in addition to warnings and precautions for hepatotoxicity, infections, neutropenia, hypersensitivity and other administrative reactions and embryo-fetal toxicity.1 The most common adverse reactions (>20%) in the safety population of MajesTEC-1 (n=165) were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea.1 The most common Grade 3 to 4 laboratory abnormalities (>20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin and decreased platelets.1 TECVAYLI™ is available only through a restricted program called the TECVAYLI™ Risk Evaluation and Mitigation Strategy.1 Details of the Important Safety Information are included below. TECVAYLI™ is supplied as 30mg/3mL and 153mg/1.7mL single-dose vials.

"In the pivotal teclistamab study, we have continued to observe positive results in heavily pretreated patients with relapsed or refractory multiple myeloma," said Ajai Chari, M.D., Professor of Medicine, Division of Hematology and Medical Oncology at the Icahn School of Medicine at Mount Sinai and study investigator.‡ "As a clinician and researcher, I see first-hand the human toll of this incurable disease. 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."

About the MajesTEC-1 Study

MajesTEC-1 (NCT04557098, NCT03145181), is a Phase 1/2 single-arm, open-label, multicohort, multicenter dose-escalation study to evaluate the safety and efficacy of TECVAYLI™ in adults with relapsed or refractory multiple myeloma who received three or more prior lines of therapy.

Phase 1 of the study (NCT03145181) was conducted in two parts: dose escalation (Part 1) and dose expansion (Part 2). It evaluated safety, tolerability, pharmacokinetics and preliminary efficacy of TECVAYLI™ in adult participants with relapsed or refractory multiple myeloma. Study criteria excluded patients who had stroke, seizure, allogenic stem cell transplantation within the past six months, Eastern Cooperative Oncology Group (ECOG) performance score of 2 or higher, known active CNS involvement or clinical signs of meningeal involvement of multiple myeloma, or active or documented history of autoimmune disease, with the exception of vitiligo, Type 1 diabetes, and prior autoimmune thyroiditis.

Phase 2 of the study (NCT04557098) evaluated the efficacy of TECVAYLI™ at the recommended phase 2 dose (RP2D), established at subcutaneous 1.5 mg/kg weekly, as measured by ORR. During week one, participants received step-up doses of TECVAYLI™ subcutaneous (0.06 and 0.3 mg/kg). Subsequently, participants received weekly treatment doses of TECVAYLI™ subcutaneous 1.5 mg/kg until disease progression or unacceptable toxicity. Efficacy was established based on ORR as determined by the Independent Review Committee (IRC) assessment using International Myeloma Working Group (IMWG) 2016 criteria.

The primary endpoint was overall response rate or unacceptable toxicity. Secondary endpoints included duration of response, very good partial response, complete response, stringent complete response, time to response, minimal residual disease status, progression-free survival, overall survival, safety, pharmacokinetics, immunogenicity and patient-reported outcomes.