J&J nabs FDA okay for BCMA bispecific Tecvayli

Johnson & Johnson has secured another regulatory approval for its BCMAxCD3 bispecific antibody for multiple myeloma – Tecvayli – adding to the wide range of therapies available for the blood cancer.

The US FDA has cleared Tecvayli (teclistamab) for the treatment of adults 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.

It joins a number of other BCMA-directed therapies for multiple myeloma, including GSK's first-to-market antibody-drug conjugate Blenrep (belantamab mafodotin), Bristol-Myers Squibb/bluebird bio's CAR-T therapy Abecma (idecabtagene vicleucel), and J&J/Legend Biotech's CAR-T Carvykti (ciltacabtagene autoleucel).

J&J is emphasising Tecvayli's subcutaneous route of administration, which avoids the intravenous infusion route required for the other three therapies, and that it is an off-the-shelf therapy unlike Abecma and Carvykti, which need cells to be harvested from the patient, modified and grown in the lab, and then reinfused.

CAR-Ts are also notoriously hard to tolerate, but that won't necessarily be in Tecvayli's favour, as the bispecific carries its own side-effect burden, including cytokine release syndrome and neurotoxicity, which means that it will have to be prescribed under a risk evaluation and mitigation strategy (REMS).

The FDA approval comes after a green light for Tecvayli in the EU and is based on the results of the phase 2 MajesTEC-1 study, which found that the bispecific antibody achieved an overall response rate of 62% and a complete response rate of 28% in a heavily pre-treated patient population.

Its efficacy rivals that of the CAR-T therapies, with the added convenience of being ready to administer on demand, and for those reasons bispecific antibodies are increasingly seen as a threat to cell-based therapies for blood cancers.

Tecvayli joins Roche's recently-approved CD20xCD3 bispecific Lunsumio (mosunetuzumab) for follicular lymphoma – also approved in the EU ahead of the US – which is competing with Novartis' Kymriah (tisagenlecleucel) and Gilead Sciences' Yescarta (axicabtagene ciloleucel), both CD19-targeting CAR-Ts.

The approved label for Tecvayli in the US also seems a little more restricted that in Europe, however, where the drug can be used after three prior lines of therapy rather than four, but its fifth-line use puts it on level pegging with Blenrep, Abecma, and Carvykti.

All the drugs' developers are working to move them up the treatment pathway. For example, J&J is combining Tecvayli with its CD38-targeting antibody Darzalex (daratumumab) in the phase 3 MajesTEC-3 trial in multiple myeloma patients who have received one to three prior lines of therapy.

A Reuters report notes that Tecvayli will become available on or around 4 November with a list price of $39,500 per month, with the overall cost ranging between $355,000 and $395,000 per patient for a nine- to 10-month course.