Talquetamab

In a newly released draft guidance, the FDA laid out how drugmakers can lean on minimal residual disease (MRD) and complete response (CR) as primary endpoints to accelerate multiple myeloma therapies toward approval.The FDA noted that overall response rates (ORRs) with new therapies now routinely exceed 60-70% in relapsed disease and 90% in newly diagnosed patients. That success has blunted the usefulness of ORR as a metric to decide accelerated approvals because proving statistically significant differences now means companies have to conduct "infeasibly large" trials. "More sensitive response assessments will allow for continued expeditious drug development," the FDA said.MRD are the tiny traces of cancer cells that can linger in the bone marrow even after a patient appears to be in remission. An FDA advisory panel in 2024 unanimously endorsed using MRD negativity as a surrogate endpoint for myeloma trials after two meta-analyses showed that MRD-negative status strongly correlates with better progression-free survival (PFS) and overall survival (OS).According to the draft guidance, MRD data from single-arm trials can support accelerated approval, though "randomised trials are preferred, as they provide robust assessments for comparative safety" and allow ongoing evaluation of longer-term outcomes like PFS or OS. Sponsors should also "adequately justify the assumed magnitude" of treatment difference for MRD negativity between arms, with MRD assessed at a threshold of at least 1 in 105 residual tumour cells. Additionally, the FDA noted that MRD as an endpoint is appropriate only in specific patient populations and disease settings, saying there isn't enough data currently to consider it in the maintenance therapy or in populations such as smouldering multiple myeloma.Meanwhile, the FDA said CR is a recognised prognostic biomarker, as patients who achieve CR have better long-term outcomes, based on pooled analysis of clinical trial data. While the principles that underpin using MRD as an endpoint also apply to CR, there are some specific considerations, including the need for adequate follow-up in order to establish the durability of CR.J&J 'excited' about optionJohnson & Johnson — which markets several myeloma therapies, including CD38-targeting antibody Darzalex (daratumumab), BCMA-targeting CAR-T cell therapy Carvykti (ciltacabtagene autoleucel) and bispecific antibodies like Tecvayli (teclistamab) and Talvey (talquetamab) — welcomed the new guidance on an earnings call Wednesday."Much of the evidence behind that, frankly, was pioneered by J&J over the years, so we're excited that [MRD] is an option," said John Reed, executive vice president, innovative medicine, R&D. "A place where this could be particularly apropos is with our new trispecific antibody for myeloma, ramantamig (JNJ-79635322), which brings the features of both [Tecvayli] and [Talvey] into a single molecule."However, as this only applies to the US, Reed said the company will still have to deliver PFS and OS data for other territories, "so I suspect that will continue to be an element of our protocols."Comments on the draft can be submitted to the FDA until March 23.

Just a month after Johnson & Johnson reported a trial win pairing its multiple myeloma treatments Tecvayli and Darzalex, the company has revealed the success of another study in which Tecvayli excelled as a solo agent. Just a month after Johnson & Johnson reported the success of a high-profile study pairing its blood cancer treatments Tecvayli and Darzalex, the company has revealed another trial win in which Tecvayli excelled as a solo agent in certain patients with multiple myeloma.The bispecific BCMA-directed CD3 T-cell engager reduced the risk of disease progression or death by 71%—and the risk of death by 40%—compared to a standard-of-care (SOC) regimen in a study population predominantly resistant to use of an anti-CD38 therapy and Bristol Myers Squibb’s Revlimid (lenalidomide).In the phase 3 trial, dubbed MajesTEC-9, Tecvayli topped SOC regimens, which included a combination of BMS’ Pomalyst plus Takeda’s Velcade and the corticosteroid dexamethasone (PVd), as well as a cocktail of Amgen’s Kyprolis and dexamethasone (Kd) in patients who had received between one and three previous lines of therapy.All patients in the study received a prior anti-CD38 monoclonal antibody and lenalidomide. Of the enrolled patients, 85% were refractory to anti-CD38 treatment, 79% were resistant to lenalidomide and 90% were resistant to their most recent line of therapy.“The MajesTEC-9 results reinforce the potential of Tecvayli to transform treatment earlier in the multiple myeloma journey, with an immunotherapy regimen widely available for all appropriate patients, including those commonly treated in the community setting,” Roberto Mina, M.D., a professor at the Winship Cancer Institute of Emory University, said in a statement.Top-line data were confirmed following a pre-specified interim analysis, J&J said. Full results of the study will be presented at a future major medical conference and shared with global health authorities, the company added.The new results build on the success of the late-stage MajesTEC-3 study in which Tecvayli and Darzalex topped the SOC combos of Darzalex and dexamethasone paired with either Pomalyst or Velcade in second-line multiple myeloma patients.The Tecvayli-Darzalex regimen reduced the risk of death by 54% in that study. While the median overall survival (OS) length was not reached for either treatment group, the three-year OS rate was 83% for the experimental arm versus 65% for the control arm. The combo also pared down the risk of progression or death by 83%.Together, the results of MajesTEC-3 and MajesTEC-9 help establish Tecvayli as an “essential therapy for patients as early as first relapse,” Mina added in J&J's latest release. J&J is also exploring other multiple myeloma combinations for Tecvayli, including one with the company’s bispecific antibody Talvey, which was approved in 2023.Multiple myeloma is characterized by high rates of relapse, J&J said. Despite recent advances in treatment, a significant unmet need remains for well–tolerated therapies, particularly in earlier lines of therapy for patients refractory to anti–CD38 monoclonal antibodies and lenalidomide.When Tecvayli was approved by the FDA in 2022 for fourth-line use in multiple myeloma, it became the first drug of its kind on the market. The nod came shortly after officials in Europe blessed Tecvayli for third-line use in the indication. Tecvayli comes with some known potential side effects, including cytokine release syndrome and neurologic toxicity. Its label includes a boxed warning, and the treatment is available only through a monitoring program known as Risk Evaluation and Mitigation Strategies.Darzalex, which has been on the market for a decade, is a cash cow for J&J, generating sales of $11.7 billion in 2024. The drug is on its way to significantly top that figure for 2025, with sales of $10.4 billion reported through the first nine months of last year. Meanwhile, sales for Tecvayli are scaling up quickly, from $549 million in 2024 to $494 million through the first three quarters of 2025.